155 results on '"Makiko Taniai"'
Search Results
2. Analysis of genetic factors associated with fatty liver disease‐related hepatocellular carcinoma
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Tomomi Kogiso, Yuri Ogasawara, Kentaro Horiuchi, Makiko Taniai, and Katsutoshi Tokushige
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17‐beta dehydrogenase 13 ,fatty liver disease ,hepatocellular carcinoma ,patatin‐like phospholipase 3 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Aim Single‐nucleotide polymorphisms (SNPs) in PNPLA3 and hydroxysteroid 17‐beta dehydrogenase 13 (HSD17B13) genes are associated with fatty liver disease (FLD) progression and carcinogenesis. In the present study, we evaluated the characteristics of Japanese FLD patients according to HSD17B13 polymorphisms. Methods We enrolled 402 patients who were clinically and pathologically diagnosed with FLD (alcoholic: 63 cases, nonalcoholic: 339 cases) at our hospital in 1990–2018 (228 males; median age: 54.9 [14.6–83.6] years). FLD patients with HSD17B13 A/A (212 cases) and others (A/AA or AA/AA; 190 cases) were compared. Results Compared to patients with HSD17B13 A/A and others, those with the A/A genotype showed increased incidence of hepatocellular carcinoma (HCC) (A/A vs. others; 18.4% vs. 9.5%, p = 0.01), cardiovascular diseases (14.2% vs. 4.2%, p
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- 2023
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3. Outcomes of fatty liver disease with and without metabolic comorbidities and risk factors for mortality
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Yuri Ogasawara, Tomomi Kogiso, Kentaro Horiuchi, Makiko Taniai, and Katsutoshi Tokushige
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metabolic‐associated fatty liver disease ,mortality ,non‐alcoholic fatty liver disease ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Background and Aim As the clinical course of metabolic‐associated fatty liver disease (MAFLD) is unclear, we compared the clinical courses of MAFLD and non‐alcoholic FLD (NAFLD). Methods Asian FLD patients (n = 987) from 1991 to 2021 (biopsy‐proven in 939) were enrolled. The patients were divided into NAFLD (N‐alone, n = 92), both MAFLD and N (M&N, n = 785), and M‐alone (n = 90) groups. Clinical features, complications, and survival rates were compared among the three groups. Risk factors of mortality were subjected to Cox regression analysis. Results The N‐alone group patients were significantly younger (N alone, M&N, and M alone: 50, 53, and 57 years, respectively), more frequently male (54.3%, 52.6%, and 37.8%), and had a low body mass index (BMI, 23.1, 27.1, and 26.7 kg/m2) and FIB‐4 index (1.20, 1.46, and 2.10). Hypopituitarism (5.4%) and hypothyroidism (7.6%) were significantly observed in the N‐alone group. Hepatocellular carcinoma (HCC) developed in 0.0%, 4.2%, and 3.5% of the cases, and extrahepatic malignancies in 6.8%, 8.4%, and 4.7% of the cases, respectively, with no significant differences. The cardiovascular event rate was significantly higher in the M‐alone group (1, 37, and 11 cases, P
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- 2023
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4. Risk factors for fatty pancreas and effects of fatty infiltration on pancreatic cancer
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Nao Otsuka, Kyoko Shimizu, Makiko Taniai, and Katsutoshi Tokushige
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pancreatic steatosis ,pancreatic cancer ,macrophage ,pancreatic acinar cell ,autophagy dysfunction ,Physiology ,QP1-981 - Abstract
Objective: This study clarified the risk factors and pathophysiology of pancreatic cancer by examining the factors associated with fatty pancreas.Methods: The degree of fatty pancreas, background factors, and incidence of pancreatic cancer were examined among nonalcoholic fatty liver disease (NAFLD) patients (n = 281) and intraductal papillary mucinous neoplasm (IPMN) patients with a family history of pancreatic cancer (n = 38). The presence of fatty pancreas was confirmed by the pancreatic CT value/splenic CT value ratio (P/S ratio). Immunohistochemical staining was performed on 10 cases with fatty pancreas, confirmed via postoperative pathology.Results: Fatty pancreas occurred in 126 patients (44.8%) in the NAFLD group who were older (p = 0.0002) and more likely to have hypertension (p < 0.0001). The IPMN group had 18 patients (47.4%) with fatty pancreas, included more men than women (p = 0.0056), and was more likely to have patients with hypertension (p = 0.0010). On histological examination, a significant infiltration of adipocytes into the acini from the pancreatic interstitium induced atrophy of the pancreatic parenchyma, and both M1 and M2 macrophages were detected in the area where adipocytes invaded the pancreatic parenchyma. Accumulation of p62 and increased positive staining of NQO1 molecules related to autophagy dysfunction were detected in pancreatic acinar cells in the fatty area, acinar-ductal metaplasia, and pancreatic cancer cells. The rate of p62-positive cell area and that of NQO1-positive cell area were significantly higher in the fatty pancreatic region than those in the control lesion (pancreatic region with few adipocyte infiltration). Furthermore, the rate of p62-positive cell area or that of NQO1-positive cell area showed strong positive correlations with the rate of fatty pancreatic lesion. These results suggest that adipocyte invasion into the pancreatic parenthyme induced macrophage infiltration and autophagy substrate p62 accumulation. High levels of NQO1 expression in the fatty area may be dependent on p62 accumulation.Conclusion: Hypertension was a significant risk factor for fatty pancreas in patients with NAFLD and IPMN. In fatty pancreas, fatty infiltration into the pancreatic parenchyme might induce autophagy dysfunction, resulting in activation of antioxidant proteins NQO1. Thus, patients with fatty pancreas require careful follow-up.
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- 2023
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5. Risk and protective factors of acute kidney injury in decompensated cirrhotic patients with ascites on tolvaptan
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Tomomi Kogiso, Yuri Ogasawara, Takaomi Sagawa, Makiko Taniai, and Katsutoshi Tokushige
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acute kidney injury ,kanamycin/rifaximin ,liver cirrhosis ,proton pump inhibitor/H2 blockers ,tolvaptan ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Background and Aim Acute kidney injury (AKI) is a life‐threatening complication of liver cirrhosis. Here, we evaluated the risk factors and characteristics of AKI in cirrhosis. Patients/Methods This was a single‐center retrospective study. A total of 199 Japanese patients with decompensated liver cirrhosis (104 men, median age 61 years) were enrolled and received tolvaptan orally. Survival rates and new onset of AKI were monitored, and risk factors were evaluated. Results Forty‐six patients (23.1%) suffered an AKI complication and exhibited significantly poorer survival (P
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- 2021
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6. Long‐term outcome of Wilson's disease complicated by liver disease
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Satoko Arai, Tomomi Kogiso, Yuri Ogasawara, Takaomi Sagawa, Makiko Taniai, and Katsutoshi Tokushige
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acute liver failure ,aspartate aminotransferase to platelet ratio index ,fibrosis‐4 index ,liver transplantation ,Wilson's disease ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Background and Aim Wilson's disease (WD) is a rare inherited disease that causes systemic copper accumulation. This study examined the long‐term course of WD patients with liver disease. Methods The 12 patients (9 female patients) enrolled in the study had a median age of 28 years (range: 19–57 years) at their first visit to our hospital. Clinical course and fibrosis markers were assessed in all patients. Results The median age at diagnosis was 24 years (range: 5–42 years). One patient had acute liver failure (ALF) and 11 patients had chronic liver disease (CLD, 5 with cirrhosis). The patients were followed‐up for >20 years. The patient with ALF underwent liver transplantation; the postoperative course during the subsequent 20 years was good. Of the six patients with CLD, liver cirrhosis developed in four patients with interrupted chelating therapy. Two of the patients with cirrhosis died; one of these two patients died at 21 years after liver transplantation. However, the remaining patients with continued treatment exhibited a favorable clinical course for 30 years and none developed hepatocellular carcinoma (HCC). The duration of chelation therapy was significantly negatively correlated (P
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- 2021
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7. Alcohol and hepatocarcinogenesis
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Makiko Taniai
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liver neoplasms ,alcoholics ,carcinogenesis, liver ,risk factors ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
An excessive alcohol intake may result in fatty liver, acute/chronic hepatitis, cirrhosis, and lead to hepatocellular carcinoma (HCC). The aim of this review is to clarify the present condition and the mechanisms of alcohol-related hepatocarcinogenesis and clinical risk factors for alcohol-related HCC. There are several possible mechanisms through which alcohol may induce hepatocarcinogenesis, including the mutagenic effects of acetaldehyde toxicity through the formation of protein and DNA adducts and the production of reactive oxygen species due to the excessive hepatic deposition of iron, changes to lipid peroxidation and metabolism, inflammation and an impaired immune response and modifications to DNA methylation. Furthermore, it has been reported that alcohol accelerates liver carcinogenesis through several signaling pathways including gut-liver axis. From a clinical perspective, it is well known that alcohol interacts with other factors, such as age, gender, viral hepatitis, obesity, and diabetes leading to an increased risk of HCC.
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- 2020
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8. Prevalence of fatty liver disease after liver transplantation and risk factors for recipients and donors
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Kentaro Horiuchi, Tomomi Kogiso, Takaomi Sagawa, Makiko Taniai, Yoshito Kotera, Hiroto Egawa, and Katsutoshi Tokushige
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Fatty liver disease (FLD) ,Liver transplantation (LT) ,Everolimus (EVL) ,Specialties of internal medicine ,RC581-951 - Abstract
Introduction and objectives: Fatty liver disease (FLD) may develop in liver transplant recipients. We investigated the recipient and donor risk factors for FLD development after liver transplantation (LT). Methods: A total of 108 liver transplant recipients (54 men [50.0%]; median age, 52 [20–68] years) treated from 2011–2020 was enrolled. Three recipients died at
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- 2022
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9. Risk factors for Fontan-associated hepatocellular carcinoma.
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Tomomi Kogiso, Takaomi Sagawa, Makiko Taniai, Eriko Shimada, Kei Inai, Tokuko Shinohara, and Katsutoshi Tokushige
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Medicine ,Science - Abstract
AimsThe incidence of hepatocellular carcinoma (HCC) in patients with Fontan-associated liver disease (i.e., FALD-HCC) has increased over time. However, the risk factors for HCC development remain unclear. Here, we compared the levels of non-invasive markers to the survival rate of FALD-HCC patients.MethodsFrom 2003 to 2021, 154 patients (66 men, 42.9%) developed liver disease after undergoing Fontan procedures. HCC was diagnosed in 15 (9.7%) (8 men, 53.3%) at a median age of 34 years (range, 21-45 years). We compared FALD-HCC and non-HCC cases; we generated marker level cutoffs using receiver operating characteristic curves. We sought to identify risk factors for HCC and mortality.ResultsThe incidence of HCC was 4.9% in FALD patients within 20 years after the Fontan procedure. Compared with non-HCC patients, FALD-HCC patients exhibited higher incidences of polysplenia and esophageal varices. At the time of HCC development, the hyaluronic acid (HA) level (p = 0.04) and the fibrosis-4 index (p = 0.02) were significantly higher in FALD-HCC patients than in non-HCC patients; the total bilirubin (T-BIL) level (p = 0.07) and the model for end-stage liver disease score [excluding the international normalized ratio (MELD-XI)] (p = 0.06) tended to be higher in FALD-HCC patients. Within approximately 20 years of the Fontan procedure, 10 patients died (survival rate, 96.9%). Kaplan-Meier curve analysis indicated that patients with T-BIL levels ≥ 2.2 mg/dL, HA levels ≥ 55.5 ng/mL, and MELD-XI scores ≥ 18.7 were at high risk of HCC, a generally poor prognosis, and both polysplenia and esophageal varices. Multivariate Cox regression analyses indicated that the complication of polysplenia [Hazard ratio (HR): 10.915] and a higher MELD-XI score (HR: 1.148, both p < 0.01) were independent risk factors for FALD-HCC.ConclusionsThe complication of polysplenia and a MELD-XI score may predict HCC development and mortality in FALD patients.
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- 2022
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10. Impact of continued administration of tolvaptan on cirrhotic patients with ascites
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Tomomi Kogiso, Takaomi Sagawa, Kazuhisa Kodama, Makiko Taniai, and Katsutoshi Tokushige
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Vasopressin V2-receptor antagonist ,Tolvaptan ,Liver cirrhosis ,Body weight reduction ,Long-term outcome ,Therapeutics. Pharmacology ,RM1-950 ,Toxicology. Poisons ,RA1190-1270 - Abstract
Abstract Background The vasopressin V2-receptor antagonist tolvaptan is used to treat cirrhotic patients with ascites. We investigated the outcome of long-term treatment. Methods This was a single-center retrospective study. Overall, 170 cirrhotic patients (95 males, median age 63 years) were enrolled and received tolvaptan orally after hospitalization for ascites, which included treatment with conventional diuretics. We compared patients who withdrew tolvaptan treatment after
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- 2018
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11. Outcomes of Japanese patients with non-alcoholic fatty liver disease according to genetic background and lifestyle-related diseases
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Tomomi Kogiso, Takaomi Sagawa, Kazuhisa Kodama, Makiko Taniai, Etsuko Hashimoto, and Katsutoshi Tokushige
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Non-alcoholic fatty liver disease (NAFLD) ,Mortality ,Single nucleotide polymorphism (SNP) ,Patatin-like phospholipase 3 (PNPLA3) ,Aldehyde dehydrogenase 2 (ALDH2) ,Specialties of internal medicine ,RC581-951 - Abstract
Introduction and objectives: Genetic background may be involved in the mechanisms of liver injury and the development of non-alcoholic fatty liver disease (NAFLD). However, its contributions to the long-term outcome of NAFLD have been unclear. Methods: We enrolled 314 Japanese patients with biopsy-confirmed NAFLD from 2000 to 2018 (161 men [51.3%]; median age, 53 [14–84] years; 114 with advanced fibrosis [37.5%]) in the patients without hepatocellular carcinoma at diagnosis. Genomic DNA was extracted from peripheral blood and single nucleotide polymorphisms (SNPs) were analyzed. Associations of mortality with patatin-like phospholipase 3 (PNPLA3) and aldehyde dehydrogenase 2 (ALDH2) were analyzed. Finally, a subgroup analysis according to lifestyle-related disease was performed. Results: During the median 7 years of follow-up, 20 patients (6.4%) died (13 liver-related [4.1%] and 7 non-liver-related deaths [2.2%]). Patients with ALDH2 (non-GG genotype) who had reduced alcohol metabolism tended to have a poor prognosis (p = 0.06). Patients carrying both risk SNPs of PNPLA3 (GG) and ALDH2 (non-GG) had a significantly poor prognosis (p = 0.01). In the subgroup analysis, patients with PNPLA3 (GG) who were non-diabetics (p = 0.06) or non-dyslipidemic (p = 0.03), with ALDH2 (non-GG) who were non-dyslipidemic (p = 0.01) or hypertensive (p = 0.03), also had a poor prognosis. The Cox analysis revealed that ALDH2 (non-GG) was associated with a poor prognosis (Hazard ratio: 4.568, 95% Confidence Interval: 1.294–16.131, p = 0.02) similar to the liver function tests. Conclusions: Genetic background may affect NAFLD prognosis and ALDH2 SNP could predict the outcome.
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- 2021
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12. Risk and protective factors of acute kidney injury in decompensated cirrhotic patients with ascites on tolvaptan
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Makiko Taniai, Takaomi Sagawa, Katsutoshi Tokushige, Yuri Ogasawara, and Tomomi Kogiso
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proton pump inhibitor/H2 blockers ,medicine.medical_specialty ,Cirrhosis ,liver cirrhosis ,kanamycin/rifaximin ,Tolvaptan ,RC799-869 ,urologic and male genital diseases ,Gastroenterology ,chemistry.chemical_compound ,Internal medicine ,Ascites ,Medicine ,Hepatic encephalopathy ,Hepatology ,tolvaptan ,business.industry ,Acute kidney injury ,Original Articles ,Diseases of the digestive system. Gastroenterology ,medicine.disease ,female genital diseases and pregnancy complications ,Rifaximin ,acute kidney injury ,chemistry ,Original Article ,medicine.symptom ,business ,Complication ,Kidney disease ,medicine.drug - Abstract
Background and Aim Acute kidney injury (AKI) is a life‐threatening complication of liver cirrhosis. Here, we evaluated the risk factors and characteristics of AKI in cirrhosis. Patients/Methods This was a single‐center retrospective study. A total of 199 Japanese patients with decompensated liver cirrhosis (104 men, median age 61 years) were enrolled and received tolvaptan orally. Survival rates and new onset of AKI were monitored, and risk factors were evaluated. Results Forty‐six patients (23.1%) suffered an AKI complication and exhibited significantly poorer survival (P, In cirrhosis, AKI incidence was increased in patients with encephalopathy and poor liver function. While proton pump inhibitor/H2 blocker or kanamycin/rifaximin treatment may reduce the risk of AKI.
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- 2021
13. Outcomes of fatty liver disease with and without metabolic comorbidities and risk factors for mortality
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Yuri Ogasawara, Tomomi Kogiso, Kentaro Horiuchi, Makiko Taniai, and Katsutoshi Tokushige
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Hepatology ,Gastroenterology - Abstract
Aims Patients with fatty liver disease (FLD) frequently have metabolic risk factors; however, the clinical course of metabolic-associated FLD (MAFLD) in Asians is unclear. We compared the clinical courses of MAFLD and nonalcoholic FLD (NAFLD). Methods Asian FLD patients (n = 987) from 1991–2021 (biopsy-proven in 939, 497 males) were enrolled. The patients were divided into non-MAFLD/NAFLD (non-M/N, n = 92), both M/N (n = 785), and M/non-N (n = 90) groups. The clinical features, complications, and survival rates were compared among the three groups. Mortality risk factors were subjected to Cox regression analysis. Results 1) Non-M/N patients were significantly younger (non-M/N, M/N, and M/non-N 50, 53, and 57 years, respectively), more frequently male (54.3, 52.6, and 37.8%), and had a low body mass index (BMI, 23.1, 27.1, and 26.7 kg/m2) and FIB-4 index (1.20, 1.46, and 2.10). Hypopituitarism (5.4%) and hypothyroidism (7.6%) were significantly observed in the non-M/N group. Hepatocellular carcinoma (HCC) developed in 0.0, 4.2, and 3.3% of the cases, and extrahepatic malignancies in 6.8, 8.4, and 4.7% of the cases, respectively, with no significant differences. The cardiovascular event rate was significantly higher in the M/non-N group (1, 37, and 11 cases, p
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- 2022
14. Evidence-based clinical practice guidelines for Liver Cirrhosis 2020
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Takemi Akahane, Tooru Shimosegawa, Hitoshi Yoshiji, Masahito Shimizu, Masayuki Kurosaki, Hiroki Nishikawa, Hisashi Hidaka, Koji Ogawa, Yoichi Hiasa, Kazuhiko Koike, Hiroto Miwa, Yoshinari Asaoka, Isao Sakaida, Takumi Kawaguchi, Tetsuo Takehara, Sumiko Nagoshi, Makiko Taniai, Nobuyuki Enomoto, Kazuaki Chayama, Shuji Terai, and Yoshiyuki Ueno
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Liver Cirrhosis ,medicine.medical_specialty ,Cirrhosis ,Complications ,medicine.medical_treatment ,Guidelines as Topic ,Review Article ,Liver transplantation ,Guidelines ,03 medical and health sciences ,0302 clinical medicine ,Hepatorenal syndrome ,Japan ,Internal medicine ,Diagnosis ,medicine ,Humans ,Intensive care medicine ,Portopulmonary hypertension ,business.industry ,Gastroenterology ,Guideline ,Hepatitis B ,Hepatology ,medicine.disease ,Treatment ,030220 oncology & carcinogenesis ,Evidence-Based Practice ,030211 gastroenterology & hepatology ,Steatohepatitis ,business - Abstract
The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japan Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.
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- 2021
15. Evidence‐based clinical practice guidelines for liver cirrhosis 2020
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Hiroto Miwa, Hitoshi Yoshiji, Takemi Akahane, Hiroki Nishikawa, Kazuhiko Koike, Masahito Shimizu, Isao Sakaida, Hisashi Hidaka, Shuji Terai, Koji Ogawa, Tooru Shimosegawa, Sumiko Nagoshi, Takumi Kawaguchi, Yoshiyuki Ueno, Tetsuo Takehara, Nobuyuki Enomoto, Makiko Taniai, Masayuki Kurosaki, Yoichi Hiasa, Yoshinari Asaoka, and Kazuaki Chayama
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medicine.medical_specialty ,Portopulmonary hypertension ,Evidence-based practice ,Cirrhosis ,Hepatology ,business.industry ,medicine.medical_treatment ,Guideline ,Liver transplantation ,medicine.disease ,Infectious Diseases ,Hepatorenal syndrome ,Internal medicine ,medicine ,Steatohepatitis ,Intensive care medicine ,business - Abstract
The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japanese Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.
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- 2021
16. Abstract 760: Characteristics of fatty liver disease-related hepatocellular carcinoma and genetic background in Japan
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Tomomi Kogiso, Yuri Ogasawara, Kentaro Horiuchi, Makiko Taniai, and Katsutoshi Tokushige
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Cancer Research ,Oncology - Abstract
Aim: A single nucleotide polymorphism (SNP) in PNPLA3 was identified as a disease susceptibility gene for fatty liver disease (FLD) and it’s associated with fibrosis progression and carcinogenesis. Additionally, mutations in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13), which encodes hepatic lipid droplet protein, have been found the involvement in various metabolic processes. Loss-of-function mutations in the human HSD17B13 gene may confer a strong protective effect on liver injury, inflammation, fibrosis, and even onset of hepatocellular carcinoma (HCC). Here, we evaluated the characteristics of Japanese patients with FLD- HCC and considered the risk factors of HCC including genetic background. Methods: We enrolled 402 patients of clinically and pathologically diagnosed with FLD (alcohol: 63, nonalcohol: 339) in our hospital from 1990-2018 (228 males, median age 54.9 [14.6-83.6] years). We analyzed the survival and new-onset HCC rates according to the etiology of FLD (alcohol and nonalcohol), hepatic fibrosis, FIB-4 index, and genetic background of PNPLA3 and HSD17B13 for consideration of the risk factors. Results: FLD-HCC was observed in 57 cases (14.2%). Comparing to the patients with HSD17B13 wild-type AA (212 cases) and mutant (A/AA or AA/AA, 190 cases), patients with wild type showed significantly increased HCC complication (wild vs. mutant; 39 [18.4%] vs. 18 [9.5%], p = 0.01) and these were tended to be high complication of hypertension (120 [56.6%] vs. 90 [47.4%], p = 0.06). In patients with mutant of HSD17B13, HCC incidence was significantly reduced in alcohol-related FLD, FIB-4 index Conclusions: Genetic background of FLD may associate with onset of HCC. Inhibiting HSD17B13 activity may prevent HCC development, especially in alcohol-related FLD and patients with low risk factors. Therefore, SNPs of gene combination with other risk factors may use for screening tool for FLD-HCC. Citation Format: Tomomi Kogiso, Yuri Ogasawara, Kentaro Horiuchi, Makiko Taniai, Katsutoshi Tokushige. Characteristics of fatty liver disease-related hepatocellular carcinoma and genetic background in Japan [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 760.
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- 2023
17. Long-term Follow-up of a Patient with Portal Hypertension and Hepatic Failure Due to Hepatic Hydatid Disease
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Shinichi Nakamura, Yuri Ogasawara, Tomomi Kogiso, Makiko Taniai, Yuki Takenaka, Katsutoshi Tokushige, Sho Yatsuji, and Miki Koroku
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Echinococcosis, Hepatic ,Abdominal pain ,medicine.medical_specialty ,Case Report ,Disease ,030204 cardiovascular system & hematology ,hepatic hydatid disease ,03 medical and health sciences ,0302 clinical medicine ,Hypertension, Portal ,parasitic diseases ,Internal Medicine ,medicine ,Humans ,Child ,Aged, 80 and over ,business.industry ,liver failure ,Liver failure ,portal hypertension ,General Medicine ,Middle Aged ,medicine.disease ,Echinococcosis ,Surgery ,echinococcosis ,Etiology ,Portal hypertension ,Female ,030211 gastroenterology & hepatology ,Hepatic Cyst ,medicine.symptom ,business ,Follow-Up Studies ,Calcification - Abstract
We observed liver failure with a presumed etiology of echinococcosis in an 89-year-old woman. Our patient had been born and then resided on Rebun Island until she was 12 years old. At 46 years old, she had been referred to our hospital due to right abdominal pain. Ultrasound had revealed multilocular cysts in the right lobe of the liver. At 84 years old, the hepatic cyst occupied nearly the entire liver with ring-shaped calcification along the cyst wall. The patient was diagnosed with decompensated cirrhosis and hepatic hydatid disease based on typical imaging and the long-term natural clinical course.
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- 2021
18. Long‐term outcome of Wilson's disease complicated by liver disease
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Tomomi Kogiso, Satoko Arai, Takaomi Sagawa, Katsutoshi Tokushige, Yuri Ogasawara, and Makiko Taniai
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medicine.medical_specialty ,Cirrhosis ,medicine.medical_treatment ,RC799-869 ,Liver transplantation ,Chronic liver disease ,Gastroenterology ,Liver disease ,Internal medicine ,medicine ,Chelation therapy ,fibrosis‐4 index ,liver transplantation ,Hepatology ,business.industry ,Original Articles ,acute liver failure ,Diseases of the digestive system. Gastroenterology ,medicine.disease ,Wilson's disease ,Hepatocellular carcinoma ,Original Article ,Liver function ,business ,aspartate aminotransferase to platelet ratio index - Abstract
Background and Aim Wilson's disease (WD) is a rare inherited disease that causes systemic copper accumulation. This study examined the long‐term course of WD patients with liver disease. Methods The 12 patients (9 female patients) enrolled in the study had a median age of 28 years (range: 19–57 years) at their first visit to our hospital. Clinical course and fibrosis markers were assessed in all patients. Results The median age at diagnosis was 24 years (range: 5–42 years). One patient had acute liver failure (ALF) and 11 patients had chronic liver disease (CLD, 5 with cirrhosis). The patients were followed‐up for >20 years. The patient with ALF underwent liver transplantation; the postoperative course during the subsequent 20 years was good. Of the six patients with CLD, liver cirrhosis developed in four patients with interrupted chelating therapy. Two of the patients with cirrhosis died; one of these two patients died at 21 years after liver transplantation. However, the remaining patients with continued treatment exhibited a favorable clinical course for 30 years and none developed hepatocellular carcinoma (HCC). The duration of chelation therapy was significantly negatively correlated (P, The duration of chelation therapy for Wilson's disease complicated by liver disease was significantly negatively correlated with the fibrosis‐4 index and aspartate aminotransferase to platelet ratio index (APRI) score at the last visit.
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- 2021
19. The utility of liver transplantation to treat acute liver failure caused by adult-onset Still’s disease: case reports
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Masayoshi Harigai, Hiroto Egawa, Yuri Ogasawara, Tomomi Kogiso, Makiko Taniai, Akiko Omori, Yoshihito Kotera, Takaomi Sagawa, Katsutoshi Tokushige, Eri Sugano, Masakazu Yamamoto, and Naoko Konda
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Adult ,medicine.medical_specialty ,Prednisolone ,medicine.medical_treatment ,Encephalopathy ,Liver transplantation ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Glucocorticoids ,Aged ,Subacute thyroiditis ,business.industry ,digestive, oral, and skin physiology ,Liver failure ,General Medicine ,Liver Failure, Acute ,Middle Aged ,Hepatology ,medicine.disease ,Colorectal surgery ,Liver Transplantation ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,business ,Still's Disease, Adult-Onset ,Abdominal surgery ,medicine.drug - Abstract
Adult-onset Still’s disease (AOSD) is an inflammatory condition commonly complicated by mild liver dysfunction. However, severe liver failure is rarely reported. We report three cases of severe acute hepatic failure (ALF) associated with AOSD. We encountered three cases of acute liver failure (ALF) with encephalopathy. Case 1 was a 75-year-old female, who was started on a steroid (prednisolone, PSL) to treat AOSD; this was gradually tapered. Two months later, severe ALF developed. She died despite an increase in the PSL dose and artificial liver support. Case 2 was a 26-year-old-female taking PSL 30 mg/day to treat subacute thyroiditis. PSL was tapered, and she received methyl PSL pulse therapy and artificial liver support, but this did not cure the ALF. Liver transplantation (LT) was performed 25 days later. Three years later, the same symptoms were observed and we diagnosed AOSD. Case 3 was a 56-year-old-female who met the AOSD criteria. PSL 50 mg/day was started and then tapered. Methyl PSL pulse therapy was prescribed to treat hemophagocytic syndrome, but she required LT on hospital day 13. In AOSD cases, ALF is rarely complicated; urgent LT should be considered only for patients with AOSD-related severe ALF.
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- 2021
20. Hepatocellular carcinoma development in diabetic patients: a nationwide survey in Japan
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Takeshi Matsumura, Kazuyoshi Kon, Etsuko Hashimoto, Hiroshi Inoue, Eiichi Araki, Hitoshi Shimano, Kosuke Kashiwabara, Naoto Kubota, Kazuhiko Koike, Ryosuke Tateishi, Yutaka Matsuyama, Hirotaka Watada, Takeshi Okanoue, Goshi Shiota, Hideo Tanaka, Sumio Watanabe, Kohjiro Ueki, Masato Kasuga, Lucid study investigators, Takumi Kawaguchi, Naoto Fujiwara, Shuichi Kaneko, Toshihide Shima, Takayoshi Sasako, Koji Uchino, Makiko Taniai, and Takafumi Senokuchi
- Subjects
Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Hepatocellular carcinoma ,FIB-4 index ,Cohort Studies ,Diabetes Complications ,Japan ,Diabetes mellitus ,Internal medicine ,Surveys and Questionnaires ,Type 2 diabetes mellitus ,Medicine ,Humans ,Registries ,Risk factor ,Prospective cohort study ,Aged ,Original Article—Liver, Pancreas, and Biliary Tract ,business.industry ,Fatty liver ,Liver Neoplasms ,Gastroenterology ,Type 2 Diabetes Mellitus ,Middle Aged ,medicine.disease ,digestive system diseases ,Logistic Models ,Diabetes Mellitus, Type 2 ,ROC Curve ,Female ,business ,Body mass index ,Cohort study - Abstract
Background Although type 2 diabetes mellitus (T2DM) is a known risk factor for hepatocellular carcinoma (HCC) development, the annual incidence in diabetes patients is far below the threshold of efficient surveillance. This study aimed to elucidate the risk factors for HCC in diabetic patients and to determine the best criteria to identify surveillance candidates. Methods The study included 239 patients with T2DM who were diagnosed with non-viral HCC between 2010 and 2015, with ≥ 5 years of follow-up at diabetes clinics of 81 teaching hospitals in Japan before HCC diagnosis, and 3277 non-HCC T2DM patients from a prospective cohort study, as controls. Clinical data at the time of and 5 years before HCC diagnosis were collected. Results The mean patient age at HCC diagnosis was approximately 73 years, and 80% of the patients were male. The proportion of patients with insulin use increased, whereas the body mass index (BMI), proportion of patients with fatty liver, fasting glucose levels, and hemoglobin A1c (HbA1c) levels decreased significantly in 5 years. In the cohort study, 18 patients developed HCC during the mean follow-up period of 4.7 years with an annual incidence of 0.11%. Multivariate logistic regression analyses showed that the FIB-4 index was an outstanding predictor of HCC development along with male sex, presence of hypertension, lower HbA1c and albumin levels, and higher BMI and gamma-glutamyl transpeptidase levels. Receiver-operating characteristic analyses showed that a FIB-4 cut-off value of 3.61 could help identify high-risk patients, with a corresponding annual HCC incidence rate of 1.1%. Conclusion A simple calculation of the FIB-4 index in diabetes clinics can be the first step toward surveillance of HCC with a non-viral etiology.
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- 2021
21. Bardet-Biedl Syndrome Caused by Skipping of SCLT1 Complicated by Microvesicular Steatohepatitis
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Kentaro Horiuchi, Makiko Taniai, Naoya Morisada, Katsutoshi Tokushige, Etsuko Hashimoto, Taito Ito, Tomomi Kogiso, Takaomi Sagawa, Motoshi Hattori, and Kenichiro Miura
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Fatty acid metabolism ,business.industry ,General Medicine ,030204 cardiovascular system & hematology ,medicine.disease ,Gastroenterology ,Obesity ,03 medical and health sciences ,chemistry.chemical_compound ,Exon ,0302 clinical medicine ,Insulin resistance ,Bardet–Biedl syndrome ,chemistry ,Internal medicine ,Retinitis pigmentosa ,Internal Medicine ,Medicine ,030211 gastroenterology & hepatology ,Steatohepatitis ,business ,Hepatic fibrosis - Abstract
We treated the case of a 22-year-old male patient with liver dysfunction. At 1 year of age, hepatic fibrosis was suspected. In addition, due to the presence of retinitis pigmentosa, renal failure, obesity, mental retardation, and hypogonadism, he was diagnosed with Bardet-Biedl syndrome (BBS). Skipping of exons 14 and 17 in the sodium channel and clathrin linker 1 (SCLT1) gene was observed. At 22 years of age, the liver enzyme levels were further elevated and a diagnosis of microvesicular steatohepatitis was made. Insulin resistance, a reduction of muscle mass, an impairment of the fatty acid metabolism, and hyperleptinemia in this syndrome may cause steatohepatitis.
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- 2020
22. A case of hemorrhage of hepatocellular carcinoma resembling a hepatic cyst arising from non-cirrhotic steatohepatitis
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Satomi Saito, Takaomi Sagawa, Katsutoshi Tokushige, Akiko Omori, Masakazu Yamamoto, Yoshihito Kotera, Kyoko Shimizu, Masayuki Nakano, Tomomi Kogiso, Makiko Taniai, and Sho Yatsuji
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Pathology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Hemorrhage ,Malignancy ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Cyst ,Aged ,medicine.diagnostic_test ,Cysts ,business.industry ,Liver Neoplasms ,Gastroenterology ,Magnetic resonance imaging ,General Medicine ,medicine.disease ,Fatty Liver ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Reticular connective tissue ,Female ,030211 gastroenterology & hepatology ,Hepatic Cyst ,Steatohepatitis ,medicine.symptom ,business - Abstract
A 70-year-old female was found to have multiple hepatic cysts at her annual checkup. In the posterior segment of the right lobe of the liver, an 81 × 67 mm circular cystic lesion was detected by contrast-enhanced computed tomography (CT). Magnetic resonance imaging (MRI) of the cyst revealed a solid component. The cyst had a capsule-like structure and non-uniform fluid accumulation suggested bleeding. Since the lesion was enlarged and malignancy could not be ruled out, it was surgically resected. Histopathologically, reticular fibers of the liver were seen in necrotic tissue and the lesion was diagnosed as a bleeding hepatocellular carcinoma (HCC). The non-cancerous liver tissue showed non-cirrhotic steatohepatitis. This was an unusual presentation of HCC.
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- 2020
23. Long‐term outcomes of non‐alcoholic fatty liver disease and the risk factors for mortality and hepatocellular carcinoma in a Japanese population
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Etsuko Hashimoto, Tomomi Kogiso, Katsutoshi Tokushige, Kazuhisa Kodama, Makiko Taniai, and Takaomi Sagawa
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Liver Cirrhosis ,Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Time Factors ,Comorbidity ,Disease ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Asian People ,Japan ,Non-alcoholic Fatty Liver Disease ,Predictive Value of Tests ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Risk factor ,Retrospective Studies ,Hepatology ,Platelet Count ,business.industry ,Incidence (epidemiology) ,Liver Neoplasms ,Fatty liver ,Age Factors ,Middle Aged ,medicine.disease ,digestive system diseases ,Survival Rate ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Female ,030211 gastroenterology & hepatology ,business ,Hepatic fibrosis ,Dyslipidemia ,Follow-Up Studies - Abstract
BACKGROUND AND AIM The incidence of mortality and hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD) has been reported, but the long-term outcomes of Japanese patients with NAFLD are not fully evaluated. METHODS We enrolled 365 Japanese patients with biopsy-confirmed NAFLD (1990-2008) followed for ≥ 6 months: 185 males (50.7%); median age (54 years); advanced fibrosis 108 (29.8%); HCC, n = 26 (7.1%); diabetes, n = 191 (52.3%); dyslipidemia, n = 234 (64.1%); and hypertension, n = 193 (52.9%). We analyzed the survival and new-onset HCC rates for hepatic fibrosis as well as complications and the treatment of lifestyle-related diseases. RESULTS During the median 7.1-year follow-up, 44 patients (12.1%) died: n = 28 liver-related (10 years liver-related death, 9.4%) and n = 16 non-liver-related deaths (10 years non-liver-related death, 4.9%). Both incidence rates were significantly higher in the advanced fibrosis group. The incidence of HCC at 10 years was 20.1% in the advanced fibrosis group, and the mortality was increased in patients with higher age, history of HCC, lower seru\m level of albumin, higher level of γ-glutamyltransferase, and insulin treatment for diabetes. Risk factors for HCC onset were higher levels of aspartate aminotransferase and triglyceride and hypertension treatment. Platelet count
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- 2020
24. I. Epidemiology of Non-alcoholic Fatty Liver Disease/Non-alcoholic Steatohepatitis
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Makiko Taniai
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medicine.medical_specialty ,business.industry ,Internal medicine ,Epidemiology ,Fatty liver ,Medicine ,Non alcoholic ,General Medicine ,Disease ,Steatohepatitis ,business ,medicine.disease ,Gastroenterology - Published
- 2020
25. Transition in the etiology of liver cirrhosis in Japan: a nationwide survey
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Akinobu Takaki, Kohichiroh Yasui, Tatsuya Kanto, Akio Ido, Hiroki Nishikawa, Yoichi Hiasa, Yasuhiro Takikawa, Makiko Taniai, Toru Ishikawa, Masayuki Kurosaki, Yoshiyuki Ueno, Koichi Takaguchi, Shuhei Nishiguchi, Shuhei Hige, and Hirayuki Enomoto
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Liver Cirrhosis ,Male ,Nonalcoholic steatohepatitis ,medicine.medical_specialty ,Cirrhosis ,Etiology ,Disease ,Nationwide survey ,Gastroenterology ,Japan ,Non-alcoholic Fatty Liver Disease ,Surveys and Questionnaires ,Internal medicine ,Humans ,Medicine ,Viral hepatitis ,Liver Diseases, Alcoholic ,Aged ,Original Article—Liver, Pancreas, and Biliary Tract ,business.industry ,Middle Aged ,Hepatology ,Hepatitis B ,medicine.disease ,Hepatitis C ,Female ,business ,Abdominal surgery - Abstract
Background To assess the recent real-world changes in the etiologies of liver cirrhosis (LC) in Japan, we conducted a nationwide survey in the annual meeting of the Japan Society of Hepatology (JSH). Methods We investigated the etiologies of LC patients accumulated from 68 participants in 79 institutions (N = 48,621). We next assessed changing trends in the etiologies of LC by analyzing cases in which the year of diagnosis was available (N = 45,834). We further evaluated the transition in the real number of newly identified LC patients by assessing data from 36 hospitals with complete datasets for 2008–2016 (N = 18,358). Results In the overall data, HCV infection (48.2%) was the leading cause of LC in Japan, and HBV infection (11.5%) was the third-most common cause. Regarding the transition in the etiologies of LC, the contribution of viral hepatitis-related LC dropped from 73.4 to 49.7%. Among the non-viral etiologies, alcoholic-related disease (ALD) and nonalcoholic steatohepatitis (NASH)-related LC showed a notable increase (from 13.7 to 24.9% and from 2.0 to 9.1%, respectively). Regarding the real numbers of newly diagnosed patients from 2008 to 2016, the numbers of patients with viral hepatitis-related LC decreased, while the numbers of patients with non-viral LC increased. Conclusions HCV has remained the main cause of LC in Japan; however, the contribution of viral hepatitis as an etiology of LC is suggested to have been decreasing. In addition, non-viral LC, such as ALD-related LC and NASH-related LC, is suggested to have increased as etiologies of LC in Japan.
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- 2019
26. Atypical Sarcoidosis Diagnosed by Massive Splenomegaly
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Satomi Saito, Shunichi Ariizumi, Yuki Yamanashi, Masakazu Yamamoto, Makiko Taniai, Katsutoshi Tokushige, Tomomi Kogiso, and Kazuhisa Kodama
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Liver sarcoidosis ,Pathology ,medicine.medical_specialty ,Sarcoidosis ,Pancytopenia ,medicine.medical_treatment ,Biopsy ,Splenectomy ,Massive splenomegaly ,Hepatosplenomegaly ,liver sarcoidosis ,Spleen ,Case Report ,030204 cardiovascular system & hematology ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal Medicine ,medicine ,Humans ,Granuloma ,medicine.diagnostic_test ,business.industry ,General Medicine ,medicine.disease ,and splenectomy ,medicine.anatomical_structure ,Liver biopsy ,massive splenomegaly ,Splenomegaly ,030211 gastroenterology & hepatology ,Female ,Muramidase ,medicine.symptom ,business - Abstract
We examined a 22-year-old woman who was admitted to our hospital with abdominal distention. At 19 years of age, the patient presented with hepatosplenomegaly. She was examined several times in another hospital; however, the cause was unidentified. Our evaluation showed severe pancytopenia and a spleen 13×24 cm in size. The serum levels of angiotensin-converting enzyme and lysozyme were elevated. She was diagnosed with liver sarcoidosis based on non-caseating epithelioid granuloma in liver biopsy tissue. To improve the symptoms, splenectomy was performed, and her pancytopenia and symptoms improved. Sarcoidosis should be considered in cases of massive splenomegaly.
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- 2019
27. Prevalence of fatty liver disease after liver transplantation and risk factors for recipients and donors
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Kentaro Horiuchi, Tomomi Kogiso, Takaomi Sagawa, Makiko Taniai, Yoshito Kotera, Hiroto Egawa, and Katsutoshi Tokushige
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Male ,Hepatology ,fungi ,Specialties of internal medicine ,General Medicine ,Fatty liver disease (FLD) ,Middle Aged ,Liver transplantation (LT) ,Tissue Donors ,Liver Transplantation ,Everolimus (EVL) ,Treatment Outcome ,RC581-951 ,Non-alcoholic Fatty Liver Disease ,Risk Factors ,Living Donors ,Prevalence ,Humans ,Female ,Prospective Studies ,Retrospective Studies - Abstract
Introduction and objectives: Fatty liver disease (FLD) may develop in liver transplant recipients. We investigated the recipient and donor risk factors for FLD development after liver transplantation (LT). Methods: A total of 108 liver transplant recipients (54 men [50.0%]; median age, 52 [20–68] years) treated from 2011–2020 was enrolled. Three recipients died at
- Published
- 2021
28. Corrigendum to ‘An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs’ [J Hepatol 2021;75(3):572–581]
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Heather J. Cordell, James J. Fryett, Kazuko Ueno, Rebecca Darlay, Yoshihiro Aiba, Yuki Hitomi, Minae Kawashima, Nao Nishida, Seik-Soon Khor, Olivier Gervais, Yosuke Kawai, Masao Nagasaki, Katsushi Tokunaga, Ruqi Tang, Yongyong Shi, Zhiqiang Li, Brian D. Juran, Elizabeth J. Atkinson, Alessio Gerussi, Marco Carbone, Rosanna Asselta, Angela Cheung, Mariza de Andrade, Aris Baras, Julie Horowitz, Manuel A.R. Ferreira, Dylan Sun, David E. Jones, Steven Flack, Ann Spicer, Victoria L. Mulcahy, Jinyoung Byun, Younghun Han, Richard N. Sandford, Konstantinos N. Lazaridis, Christopher I. Amos, Gideon M. Hirschfield, Michael F. Seldin, Pietro Invernizzi, Katherine A. Siminovitch, Xiong Ma, Minoru Nakamura, George F. Mells, Andrew Mason, Catherine Vincent, Gang Xie, Jinyi Zhang, Andrea Affronti, Piero L. Almasio, Domenico Alvaro, Pietro Andreone, Angelo Andriulli, Francesco Azzaroli, Pier Maria Battezzati, Antonio Benedetti, Maria Consiglia Bragazzi, Maurizia Brunetto, Savino Bruno, Vincenza Calvaruso, Vincenzo Cardinale, Giovanni Casella, Nora Cazzagon, Antonio Ciaccio, Barbara Coco, Agostino Colli, Guido Colloredo, Massimo Colombo, Silvia Colombo, Laura Cristoferi, Carmela Cursaro, Lory Saveria Crocè, Andrea Crosignani, Daphne D’Amato, Francesca Donato, Gianfranco Elia, Luca Fabris, Stefano Fagiuoli, Carlo Ferrari, Annarosa Floreani, Andrea Galli, Edoardo Giannini, Ignazio Grattagliano, Pietro Lampertico, Ana Lleo, Federica Malinverno, Clara Mancuso, Fabio Marra, Marco Marzioni, Sara Massironi, Alberto Mattalia, Luca Miele, Chiara Milani, Lorenzo Morini, Filomena Morisco, Luigi Muratori, Paolo Muratori, Grazia A. Niro, Sarah O’Donnell, Antonio Picciotto, Piero Portincasa, Cristina Rigamonti, Vincenzo Ronca, Floriano Rosina, Giancarlo Spinzi, Mario Strazzabosco, Mirko Tarocchi, Claudio Tiribelli, Pierluigi Toniutto, Luca Valenti, Maria Vinci, Massimo Zuin, Hitomi Nakamura, Seigo Abiru, Shinya Nagaoka, Atsumasa Komori, Hiroshi Yatsuhashi, Hiromi Ishibashi, Masahiro Ito, Kiyoshi Migita, Hiromasa Ohira, Shinji Katsushima, Atsushi Naganuma, Kazuhiro Sugi, Tatsuji Komatsu, Tomohiko Mannami, Kouki Matsushita, Kaname Yoshizawa, Fujio Makita, Toshiki Nikami, Hideo Nishimura, Hiroshi Kouno, Hirotaka Kouno, Hajime Ota, Takuya Komura, Yoko Nakamura, Masaaki Shimada, Noboru Hirashima, Toshiki Komeda, Keisuke Ario, Makoto Nakamuta, Tsutomu Yamashita, Kiyoshi Furuta, Masahiro Kikuchi, Noriaki Naeshiro, Hironao Takahashi, Yutaka Mano, Seiji Tsunematsu, Iwao Yabuuchi, Yusuke Shimada, Kazuhiko Yamauchi, Rie Sugimoto, Hironori Sakai, Eiji Mita, Masaharu Koda, Satoru Tsuruta, Hiroshi Kamitsukasa, Takeaki Sato, Naohiko Masaki, Tatsuro Kobata, Nobuyoshi Fukushima, Yukio Ohara, Toyokichi Muro, Eiichi Takesaki, Hitoshi Takaki, Tetsuo Yamamoto, Michio Kato, Yuko Nagaoki, Shigeki Hayashi, Jinya Ishida, Yukio Watanabe, Masakazu Kobayashi, Michiaki Koga, Takeo Saoshiro, Michiyasu Yagura, Keisuke Hirata, Atsushu Tanaka, Hajime Takikawa, Mikio Zeniya, Masanori Abe, Morikazu Onji, Shuichi Kaneko, Masao Honda, Kuniaki Arai, Teruko Arinaga-Hino, Etsuko Hashimoto, Makiko Taniai, Takeji Umemura, Satoru Joshita, Kazuhiko Nakao, Tatsuki Ichikawa, Hidetaka Shibata, Satoshi Yamagiwa, Masataka Seike, Koichi Honda, Shotaro Sakisaka, Yasuaki Takeyama, Masaru Harada, Michio Senju, Osamu Yokosuka, Tatsuo Kanda, Yoshiyuki Ueno, Kentaro Kikuchi, Hirotoshi Ebinuma, Takashi Himoto, Michio Yasunami, Kazumoto Murata, Masashi Mizokami, Kazuhito Kawata, Shinji Shimoda, Yasuhiro Miyake, Akinobu Takaki, Kazuhide Yamamoto, Katsuji Hirano, Takafumi Ichida, Akio Ido, Hirohito Tsubouchi, Kazuaki Chayama, Kenichi Harada, Yasuni Nakanuma, Yoshihiko Maehara, Akinobu Taketomi, Ken Shirabe, Yuji Soejima, Akira Mori, Shintaro Yagi, Shinji Uemoto, Egawa H, Tomohiro Tanaka, Noriyo Yamashiki, Sumito Tamura, Yasuhiro Sugawara, Norihiro Kokudo, Naga Chalasani, Vel Luketic, Joseph Odin, Kapil Chopra, Goncalo Abecasis, Michael Cantor, Giovanni Coppola, Aris Economides, Luca A. Lotta, John D. Overton, Jeffrey G. Reid, Alan Shuldiner, Christina Beechert, Caitlin Forsythe, Erin D. Fuller, Zhenhua Gu, Michael Lattari, Alexander Lopez, Thomas D. Schleicher, Maria Sotiropoulos Padilla, Karina Toledo, Louis Widom, Sarah E. Wolf, Manasi Pradhan, Kia Manoochehri, Ricardo H. Ulloa, Xiaodong Bai, Suganthi Balasubramanian, Leland Barnard, Andrew Blumenfeld, Gisu Eom, Lukas Habegger, Alicia Hawes, Shareef Khalid, Evan K. Maxwell, William Salerno, Jeffrey C. Staples, Marcus B. Jones, Lyndon J. Mitnaul, Richard Sturgess, Christopher Healey, Andrew Yeoman, Anton V.J. Gunasekera, Paul Kooner, Kapil Kapur, V. Sathyanarayana, Yiannis Kallis, Javaid Subhani, Rory Harvey, Roger McCorry, Paul Rooney, David Ramanaden, Richard Evans, Thiriloganathan Mathialahan, Jaber Gasem, Christopher Shorrock, Mahesh Bhalme, Paul Southern, Jeremy A. Tibble, David A. Gorard, Susan Jones, George Mells, Victoria Mulcahy, Brijesh Srivastava, Matthew R. Foxton, Carole E. Collins, David Elphick, Mazn Karmo, Francisco Porras-Perez, Michael Mendall, Tom Yapp, Minesh Patel, Roland Ede, Joanne Sayer, James Jupp, Neil Fisher, Martyn J. Carter, Konrad Koss, Jayshri Shah, Andrzej Piotrowicz, Glyn Scott, Charles Grimley, Ian R. Gooding, Simon Williams, Judith Tidbury, Guan Lim, Kuldeep Cheent, Sass Levi, Dina Mansour, Matilda Beckley, Coral Hollywood, Terry Wong, Richard Marley, John Ramage, Harriet M. Gordon, Jo Ridpath, Theodore Ngatchu, Vijay Paul Bob Grover, Ray G. Shidrawi, George Abouda, L. Corless, Mark Narain, Ian Rees, Ashley Brown, Simon Taylor-Robinson, Joy Wilkins, Leonie Grellier, Paul Banim, Debasish Das, Michael A. Heneghan, Howard Curtis, Helen C. Matthews, Faiyaz Mohammed, Mark Aldersley, Raj Srirajaskanthan, Giles Walker, Alistair McNair, Amar Sharif, Sambit Sen, George Bird, Martin I. Prince, Geeta Prasad, Paul Kitchen, Adrian Barnardo, Chirag Oza, Nurani N. Sivaramakrishnan, Prakash Gupta, Amir Shah, Chris D.J. Evans, Subrata Saha, Katharine Pollock, Peter Bramley, Ashis Mukhopadhya, Stephen T. Barclay, Natasha McDonald, Andrew J. Bathgate, Kelvin Palmer, John F. Dillon, Simon M. Rushbrook, Robert Przemioslo, Chris McDonald, Andrew Millar, Cheh Tai, Stephen Mitchell, Jane Metcalf, Syed Shaukat, Mary Ninkovic, Udi Shmueli, Andrew Davis, Asifabbas Naqvi, Tom J.W. Lee, Stephen Ryder, Jane Collier, Howard Klass, Matthew E. Cramp, Nichols Sharer, Richard Aspinall, Deb Ghosh, Andrew C. Douds, Jonathan Booth, Earl Williams, Hyder Hussaini, John Christie, Steven Mann, Douglas Thorburn, Aileen Marshall, Imran Patanwala, Aftab Ala, Julia Maltby, Ray Matthew, Chris Corbett, Sam Vyas, Saket Singhal, Dermot Gleeson, Sharat Misra, Jeff Butterworth, Keith George, Tim Harding, Andrew Douglass, Harriet Mitchison, Simon Panter, Jeremy Shearman, Gary Bray, Michael Roberts, Graham Butcher, Daniel Forton, Zahid Mahmood, Matthew Cowan, Debashis Das, Chin Lye Ch'ng, Mesbah Rahman, Gregory C.A. Whatley, Emma Wesley, Aditya Mandal, Sanjiv Jain, Stephen P. Pereira, Mark Wright, Palak Trivedi, Fiona H. Gordon, Esther Unitt, Altaf Palejwala, Andrew Austin, Vishwaraj Vemala, Allister Grant, Andrew D. Higham, Alison Brind, Ray Mathew, Mark Cox, Subramaniam Ramakrishnan, Alistair King, Simon Whalley, Jocelyn Fraser, S.J. Thomson, Andrew Bell, Voi Shim Wong, Richard Kia, Ian Gee, Richard Keld, Rupert Ransford, James Gotto, and Charles Millson
- Subjects
Science & Technology ,Hepatology ,Gastroenterology & Hepatology ,Italian PBC Study Group ,Japan-PBC-GWAS Consortium ,UK-PBC Consortium ,Chinese PBC Consortium ,1103 Clinical Sciences ,US PBC Consortium ,Canadian PBC Consortium ,Life Sciences & Biomedicine ,PBC Consortia ,1117 Public Health and Health Services - Published
- 2021
29. Characteristics of acute hepatitis A virus infection before and after 2001: A hospital‐based study in Tokyo, Japan
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Somura Yoshiko, Takaomi Sagawa, Kazuhisa Kodama, Mayuko Oda, Tomomi Kogiso, Makiko Taniai, and Katsutoshi Tokushige
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,Sexual transmission ,Sexual Behavior ,Prevalence ,medicine.disease_cause ,Gastroenterology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Humans ,Tokyo ,Aged ,Retrospective Studies ,Hepatitis B virus ,Hepatology ,Coinfection ,business.industry ,Incidence (epidemiology) ,Age Factors ,Hepatitis A ,Sexually Transmitted Diseases, Viral ,Middle Aged ,Hepatitis B ,medicine.disease ,Hospitals ,030220 oncology & carcinogenesis ,Acute Disease ,Female ,030211 gastroenterology & hepatology ,Syphilis ,business ,Biomarkers - Abstract
BACKGROUND AND AIM The incidence of acute hepatitis A [AH (A)] is decreasing because of improvements in hygiene; however, cases of sporadic severe hepatitis are still being reported. We assessed the epidemiology of AH (A) in Japan. METHODS This was a hospital-based retrospective study, in which 126 AH (A) patients (96 men [76%], median age 39 [range, 19-66] years) were enrolled. Patients diagnosed with AH (A) before 2001 (n = 79) and after 2001 (n = 47) were compared. RESULTS The incidence of AH (A) showed peaks in 1990, 1999, and 2018. After 2001, one patient had hepatitis B virus, four had human immunodeficiency virus, and three had syphilis coinfections. Before and after 2001, HAV was transmitted, respectively, by raw oysters (28% and 26%), overseas travel (19% and 28%), and sexual contact (0% and 19%) (P
- Published
- 2019
30. Characteristics of non-alcoholic steatohepatitis among lean patients in Japan: Not uncommon and not always benign
- Author
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Naotake Hashimoto, Katsutoshi Tokushige, Yuuichi Ikarashi, Kazuhisa Kodama, Makiko Taniai, Maki Tobari, Nishino Takayoshi, Estuko Hashimoto, and Tomomi Kogiso
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Fatty liver ,Gastroenterology ,Single-nucleotide polymorphism ,medicine.disease ,Obesity ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,030211 gastroenterology & hepatology ,Steatohepatitis ,Steatosis ,business ,Body mass index ,Bioelectrical impedance analysis - Abstract
BACKGROUND AND AIM To elucidate features of nonobese non-alcoholic fatty liver disease (NAFLD), we assessed Japanese patients with NAFLD stratified by body mass index (BMI) and by sex. METHODS Biopsy-proven 762 NAFLD patients (404 men) were classified into three groups by the Japanese criteria: nonobese group (BMI
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- 2019
31. Hepatocellular carcinoma after direct-acting antiviral drug treatment in patients with hepatitis C virus
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Katsutoshi Tokushige, Hiroto Egawa, Makiko Taniai, Kazuhisa Kodama, Masakazu Yamamoto, Satoshi Katagiri, Tomomi Kogiso, and Takaomi Sagawa
- Subjects
Ledipasvir ,medicine.medical_specialty ,Elbasvir ,Daclatasvir ,Hepatology ,Sofosbuvir ,business.industry ,Gastroenterology ,digestive system diseases ,Ombitasvir ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,Grazoprevir ,Paritaprevir ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Asunaprevir ,030211 gastroenterology & hepatology ,business ,medicine.drug - Abstract
Background and Aim Given the use of direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV), their effects on hepatocarcinogenesis should be determined. Methods This study enrolled 349 patients with HCV who underwent DAA treatment at our hospital between 2014 and 2018. Their median age was 65 years, and 184 were male; 301 cases were of HCV serotype 1, and 48 were of serotype 2. The DAA treatment was daclatasvir/asunaprevir in 107 cases, sofosbuvir (SOF)/ledipasvir in 147 cases, ritonavir-boosted ombitasvir/paritaprevir in 28 cases, elbasvir/grazoprevir in 19 cases, and SOF/ribavirin in 48 cases. The patients' histories included hepatocellular carcinoma (HCC) in 45 cases, liver transplant (LT) in 10 cases, and kidney transplant (KT) in 17 cases. Results Sustained virological responses occurred in 335 cases (96%). DAA treatment was initiated a median of 16.3 months after HCC treatment. After DAA treatment, 15 cases (33%) had recurrence of HCC after a median of 11.6 months, and 3 cases (1%) developed de novo HCC. Six LT patients and one KT patient had HCC; however, no HCC was observed after DAA. The incidence of HCC was significantly higher in patients with multiple HCC treatments in the Cox hazard model (hazard ratio 1.664, 95% confidence interval 1.134-2.441, P < 0.01). Surgical resection or LT reduced the risk of HCC. Conclusions DAA did not increase the rate of HCC, even in immunosuppressed patients. However, careful follow-up for HCC recurrence is required in previously treated cases.
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- 2018
32. Hepatocellular carcinoma after direct‐acting antiviral drug treatment in patients with hepatitis C virus
- Author
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Tomomi, Kogiso, Takaomi, Sagawa, Kazuhisa, Kodama, Makiko, Taniai, Satoshi, Katagiri, Hiroto, Egawa, Masakazu, Yamamoto, and Katsutoshi, Tokushige
- Subjects
direct‐acting antivirals ,hepatocarcinogenesis ,Original Article ,Original Articles ,hepatocellular carcinoma ,digestive system diseases - Abstract
Background and Aim Given the use of direct‐acting antivirals (DAAs) to treat hepatitis C virus (HCV), their effects on hepatocarcinogenesis should be determined. Methods This study enrolled 349 patients with HCV who underwent DAA treatment at our hospital between 2014 and 2018. Their median age was 65 years, and 184 were male; 301 cases were of HCV serotype 1, and 48 were of serotype 2. The DAA treatment was daclatasvir/asunaprevir in 107 cases, sofosbuvir (SOF)/ledipasvir in 147 cases, ritonavir‐boosted ombitasvir/paritaprevir in 28 cases, elbasvir/grazoprevir in 19 cases, and SOF/ribavirin in 48 cases. The patients’ histories included hepatocellular carcinoma (HCC) in 45 cases, liver transplant (LT) in 10 cases, and kidney transplant (KT) in 17 cases. Results Sustained virological responses occurred in 335 cases (96%). DAA treatment was initiated a median of 16.3 months after HCC treatment. After DAA treatment, 15 cases (33%) had recurrence of HCC after a median of 11.6 months, and 3 cases (1%) developed de novo HCC. Six LT patients and one KT patient had HCC; however, no HCC was observed after DAA. The incidence of HCC was significantly higher in patients with multiple HCC treatments in the Cox hazard model (hazard ratio 1.664, 95% confidence interval 1.134–2.441, P < 0.01). Surgical resection or LT reduced the risk of HCC. Conclusions DAA did not increase the rate of HCC, even in immunosuppressed patients. However, careful follow‐up for HCC recurrence is required in previously treated cases.
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- 2018
33. Differences in the genetic backgrounds of patients with alcoholic liver disease and non-alcoholic fatty liver disease
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Tomomi Kogiso, Makiko Taniai, Etsuko Hashimoto, Kuniko Yamamoto, and Katsutoshi Tokushige
- Subjects
Alcoholic liver disease ,medicine.medical_specialty ,Cirrhosis ,endocrine system diseases ,Hepatology ,business.industry ,Fatty liver ,Gastroenterology ,nutritional and metabolic diseases ,Single-nucleotide polymorphism ,medicine.disease ,digestive system diseases ,Genotype frequency ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Internal medicine ,Genotype ,medicine ,030211 gastroenterology & hepatology ,Steatohepatitis ,business - Abstract
Background and Aim Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) have common hepatic histological features, but few studies have compared the genomic backgrounds of these two diseases. Here, we compared the genetic differences between ALD and NAFLD. Methods This study enrolled 318 Japanese patients with ALD (n = 118; male, 86%; median age, 62 years; liver cirrhosis, 58%; hepatocellular carcinoma [HCC], 31%) and NAFLD (n = 200; male, 55%; age, 61 years; cirrhosis, 19%; HCC, 12%). The genotype frequencies of 10 single nucleotide polymorphisms (SNPs) were analyzed. Results The ADH1B genotype GG and ALDH2 genotype GG were observed more frequently, and the percentage of patients with the MTP genotype GG was lower in ALD compared with NAFLD patients (ADH1B, 16 vs 4%; ALDH2 84 vs 44%; MTP 62 vs 72%, respectively; all P
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- 2018
34. Clinicopathological investigation of steatohepatitic hepatocellular carcinoma: A multicenter study using immunohistochemical analysis of adenoma-related markers
- Author
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Katsutoshi Tokushige, Masakazu Yamamoto, Masahiko Sugitani, Toshio Fukusato, Fukuo Kondo, Tadatoshi Takayama, Keiji Sano, Makiko Taniai, Etsuko Hashimoto, Maki Tobari, and Kazuhisa Kodama
- Subjects
medicine.medical_specialty ,Hepatology ,Adenoma ,business.industry ,Fatty liver ,Hepatocellular adenoma ,medicine.disease ,Gastroenterology ,digestive system diseases ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Infectious Diseases ,030220 oncology & carcinogenesis ,Internal medicine ,Hepatocellular carcinoma ,medicine ,Inflammatory Hepatocellular Adenoma ,030211 gastroenterology & hepatology ,Serum amyloid A ,Steatohepatitis ,business ,neoplasms - Abstract
AIMS Steatohepatitic hepatocellular carcinoma (SH-HCC) is a newly proposed concept, which shows histological features of steatohepatitis in HCC lesions, and it is strongly associated with metabolic syndrome (MS) and steatosis/steatohepatitis in non-cancerous lesions. Recently, a substantial number of HCC associated with MS were reported to have developed from pre-existing inflammatory hepatocellular adenoma (HCA). To elucidate the characteristic features of SH-HCC, we clinicopathologically investigated strictly diagnosed SH-HCC and non-SH-HCC (standard HCC). METHODS This was a retrospective multicenter study. A clinicopathological investigation was undertaken to compare 62 cases with SH-HCC features to 31 age- and sex-matched standard HCC cases, including an immunohistochemical study using markers for classification of HCA and diagnosis of HCC. RESULTS The characteristic features of SH-HCC compared with standard HCC include a higher rate of complications of MS, more frequent non-alcoholic fatty liver disease as an underlying liver disease, and HCC development in non-cirrhotic liver. The rate of solitary tumors showed no difference between the two groups, but the median diameter of the main tumor was greater in SH-HCCs (45 mm/20 mm, P = 0.01). The HCCs were mostly moderately differentiated, and the patterns were mainly trabecular in both groups. Positive findings for serum amyloid A and C-reactive proteins, classification markers of inflammatory HCA, were significantly higher in cancerous lesions of SH-HCC cases (50%/13%, P
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- 2018
35. [Bibliography Symposium Points of 'Cirrhosis Clinical Practice Guideline 2020']
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Hitoshi, Yoshiharu, Toru, Hidaka, Yoshiyuki, Ueno, Masahito, Shimizu, and Makiko, Taniai
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Liver Cirrhosis ,Humans - Published
- 2021
36. An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs
- Author
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Heather J. Cordell, James J. Fryett, Kazuko Ueno, Rebecca Darlay, Yoshihiro Aiba, Yuki Hitomi, Minae Kawashima, Nao Nishida, Seik-Soon Khor, Olivier Gervais, Yosuke Kawai, Masao Nagasaki, Katsushi Tokunaga, Ruqi Tang, Yongyong Shi, Zhiqiang Li, Brian D. Juran, Elizabeth J. Atkinson, Alessio Gerussi, Marco Carbone, Rosanna Asselta, Angela Cheung, Mariza de Andrade, Aris Baras, Julie Horowitz, Manuel A.R. Ferreira, Dylan Sun, David E. Jones, Steven Flack, Ann Spicer, Victoria L. Mulcahy, Jinyoung Byan, Younghun Han, Richard N. Sandford, Konstantinos N. Lazaridis, Christopher I. Amos, Gideon M. Hirschfield, Michael F. Seldin, Pietro Invernizzi, Katherine A. Siminovitch, Xiong Ma, Minoru Nakamura, George F. Mells, Andrew Mason, Catherine Vincent, Gang Xie, Jinyi Zhang, Andrea Affronti, Piero L. Almasio, Domenico Alvaro, Pietro Andreone, Angelo Andriulli, Francesco Azzaroli, Pier Maria Battezzati, Antonio Benedetti, MariaConsiglia Bragazzi, Maurizia Brunetto, Savino Bruno, Vincenza Calvaruso, Vincenzo Cardinale, Giovanni Casella, Nora Cazzagon, Antonio Ciaccio, Barbara Coco, Agostino Colli, Guido Colloredo, Massimo Colombo, Silvia Colombo, Laura Cristoferi, Carmela Cursaro, Lory Saveria Crocè, Andrea Crosignani, Daphne D’Amato, Francesca Donato, Gianfranco Elia, Luca Fabris, Stefano Fagiuoli, Carlo Ferrari, Annarosa Floreani, Andrea Galli, Edoardo Giannini, Ignazio Grattagliano, Pietro Lampertico, Ana Lleo, Federica Malinverno, Clara Mancuso, Fabio Marra, Marco Marzioni, Sara Massironi, Alberto Mattalia, Luca Miele, Chiara Milani, Lorenzo Morini, Filomena Morisco, Luigi Muratori, Paolo Muratori, Grazia A. Niro, Sarah O’Donnell, Antonio Picciotto, Piero Portincasa, Cristina Rigamonti, Vincenzo Ronca, Floriano Rosina, Giancarlo Spinzi, Mario Strazzabosco, Mirko Tarocchi, Claudio Tiribelli, Pierluigi Toniutto, Luca Valenti, Maria Vinci, Massimo Zuin, Hitomi Nakamura, Seigo Abiru, Shinya Nagaoka, Atsumasa Komori, Hiroshi Yatsuhashi, Hiromi Ishibashi, Masahiro Ito, Kiyoshi Migita, Hiromasa Ohira, Shinji Katsushima, Atsushi Naganuma, Kazuhiro Sugi, Tatsuji Komatsu, Tomohiko Mannami, Kouki Matsushita, Kaname Yoshizawa, Fujio Makita, Toshiki Nikami, Hideo Nishimura, Hiroshi Kouno, Hirotaka Kouno, Hajime Ota, Takuya Komura, Yoko Nakamura, Masaaki Shimada, Noboru Hirashima, Toshiki Komeda, Keisuke Ario, Makoto Nakamuta, Tsutomu Yamashita, Kiyoshi Furuta, Masahiro Kikuchi, Noriaki Naeshiro, Hironao Takahashi, Yutaka Mano, Seiji Tsunematsu, Iwao Yabuuchi, Yusuke Shimada, Kazuhiko Yamauchi, Rie Sugimoto, Hironori Sakai, Eiji Mita, Masaharu Koda, Satoru Tsuruta, Hiroshi Kamitsukasa, Takeaki Sato, Naohiko Masaki, Tatsuro Kobata, Nobuyoshi Fukushima, Yukio Ohara, Toyokichi Muro, Eiichi Takesaki, Hitoshi Takaki, Tetsuo Yamamoto, Michio Kato, Yuko Nagaoki, Shigeki Hayashi, Jinya Ishida, Yukio Watanabe, Masakazu Kobayashi, Michiaki Koga, Takeo Saoshiro, Michiyasu Yagura, Keisuke Hirata, Atsushu Tanaka, Hajime Takikawa, Mikio Zeniya, Masanori Abe, Morikazu Onji, Shuichi Kaneko, Masao Honda, Kuniaki Arai, Teruko Arinaga-Hino, Etsuko Hashimoto, Makiko Taniai, Takeji Umemura, Satoru Joshita, Kazuhiko Nakao, Tatsuki Ichikawa, Hidetaka Shibata, Satoshi Yamagiwa, Masataka Seike, Koichi Honda, Shotaro Sakisaka, Yasuaki Takeyama, Masaru Harada, Michio Senju, Osamu Yokosuka, Tatsuo Kanda, Yoshiyuki Ueno, Kentaro Kikuchi, Hirotoshi Ebinuma, Takashi Himoto, Michio Yasunami, Kazumoto Murata, Masashi Mizokami, Kazuhito Kawata, Shinji Shimoda, Yasuhiro Miyake, Akinobu Takaki, Kazuhide Yamamoto, Katsuji Hirano, Takafumi Ichida, Akio Ido, Hirohito Tsubouchi, Kazuaki Chayama, Kenichi Harada, Yasuni Nakanuma, Yoshihiko Maehara, Akinobu Taketomi, Ken Shirabe, Yuji Soejima, Akira Mori, Shintaro Yagi, Shinji Uemoto, Egawa H, Tomohiro Tanaka, Noriyo Yamashiki, Sumito Tamura, Yasuhiro Sugawara, Norihiro Kokudo, Naga Chalasani, Vel Luketic, Joseph Odin, Kapil Chopra, Goncalo Abecasis, Michael Cantor, Giovanni Coppola, Aris Economides, Luca A. Lotta, John D. Overton, Jeffrey G. Reid, Alan Shuldiner, Christina Beechert, Caitlin Forsythe, Erin D. Fuller, Zhenhua Gu, Michael Lattari, Alexander Lopez, Thomas D. Schleicher, Maria Sotiropoulos Padilla, Karina Toledo, Louis Widom, Sarah E. Wolf, Manasi Pradhan, Kia Manoochehri, Ricardo H. Ulloa, Xiaodong Bai, Suganthi Balasubramanian, Leland Barnard, Andrew Blumenfeld, Gisu Eom, Lukas Habegger, Alicia Hawes, Shareef Khalid, Evan K. Maxwell, William Salerno, Jeffrey C. Staples, Marcus B. Jones, Lyndon J. Mitnaul, Richard Sturgess, Christopher Healey, Andrew Yeoman, Anton VJ. Gunasekera, Paul Kooner, Kapil Kapur, V. Sathyanarayana, Yiannis Kallis, Javaid Subhani, Rory Harvey, Roger McCorry, Paul Rooney, David Ramanaden, Richard Evans, Thiriloganathan Mathialahan, Jaber Gasem, Christopher Shorrock, Mahesh Bhalme, Paul Southern, Jeremy A. Tibble, David A. Gorard, Susan Jones, George Mells, Victoria Mulcahy, Brijesh Srivastava, Matthew R. Foxton, Carole E. Collins, David Elphick, Mazn Karmo, Francisco Porras-Perez, Michael Mendall, Tom Yapp, Minesh Patel, Roland Ede, Joanne Sayer, James Jupp, Neil Fisher, Martyn J. Carter, Konrad Koss, Jayshri Shah, Andrzej Piotrowicz, Glyn Scott, Charles Grimley, Ian R. Gooding, Simon Williams, Judith Tidbury, Guan Lim, Kuldeep Cheent, Sass Levi, Dina Mansour, Matilda Beckley, Coral Hollywood, Terry Wong, Richard Marley, John Ramage, Harriet M. Gordon, Jo Ridpath, Theodore Ngatchu, Vijay Paul Bob Grover, Ray G. Shidrawi, George Abouda, L. Corless, Mark Narain, Ian Rees, Ashley Brown, Simon Taylor-Robinson, Joy Wilkins, Leonie Grellier, Paul Banim, Debasish Das, Michael A. Heneghan, Howard Curtis, Helen C. Matthews, Faiyaz Mohammed, Mark Aldersley, Raj Srirajaskanthan, Giles Walker, Alistair McNair, Amar Sharif, Sambit Sen, George Bird, Martin I. Prince, Geeta Prasad, Paul Kitchen, Adrian Barnardo, Chirag Oza, Nurani N. Sivaramakrishnan, Prakash Gupta, Amir Shah, Chris DJ. Evans, Subrata Saha, Katharine Pollock, Peter Bramley, Ashis Mukhopadhya, Stephen T. Barclay, Natasha McDonald, Andrew J. Bathgate, Kelvin Palmer, John F. Dillon, Simon M. Rushbrook, Robert Przemioslo, Chris McDonald, Andrew Millar, Cheh Tai, Stephen Mitchell, Jane Metcalf, Syed Shaukat, Mary Ninkovic, Udi Shmueli, Andrew Davis, Asifabbas Naqvi, Tom JW. Lee, Stephen Ryder, Jane Collier, Howard Klass, Matthew E. Cramp, Nichols Sharer, Richard Aspinall, Deb Ghosh, Andrew C. Douds, Jonathan Booth, Earl Williams, Hyder Hussaini, John Christie, Steven Mann, Douglas Thorburn, Aileen Marshall, Imran Patanwala, Aftab Ala, Julia Maltby, Ray Matthew, Chris Corbett, Sam Vyas, Saket Singhal, Dermot Gleeson, Sharat Misra, Jeff Butterworth, Keith George, Tim Harding, Andrew Douglass, Harriet Mitchison, Simon Panter, Jeremy Shearman, Gary Bray, Michael Roberts, Graham Butcher, Daniel Forton, Zahid Mahmood, Matthew Cowan, Debashis Das, Chin Lye Ch’ng, Mesbah Rahman, Gregory C.A. Whatley, Emma Wesley, Aditya Mandal, Sanjiv Jain, Stephen P. Pereira, Mark Wright, Palak Trivedi, Fiona H. Gordon, Esther Unitt, Altaf Palejwala, Andrew Austin, Vishwaraj Vemala, Allister Grant, Andrew D. Higham, Alison Brind, Ray Mathew, Mark Cox, Subramaniam Ramakrishnan, Alistair King, Simon Whalley, Jocelyn Fraser, S.J. Thomson, Andrew Bell, Voi Shim Wong, Richard Kia, Ian Gee, Richard Keld, Rupert Ransford, James Gotto, Charles Millson, Cordell, H. J., Fryett, J. J., Ueno, K., Darlay, R., Aiba, Y., Hitomi, Y., Kawashima, M., Nishida, N., Khor, S. -S., Gervais, O., Kawai, Y., Nagasaki, M., Tokunaga, K., Tang, R., Shi, Y., Li, Z., Juran, B. D., Atkinson, E. J., Gerussi, A., Carbone, M., Asselta, R., Cheung, A., de Andrade, M., Baras, A., Horowitz, J., Ferreira, M. A. R., Sun, D., Jones, D. E., Flack, S., Spicer, A., Mulcahy, V. L., Byan, J., Han, Y., Sandford, R. N., Lazaridis, K. N., Amos, C. I., Hirschfield, G. M., Seldin, M. F., Invernizzi, P., Siminovitch, K. A., Ma, X., Nakamura, M., Mells, G. F., Mason, A., Vincent, C., Xie, G., Zhang, J., Affronti, A., Almasio, P. L., Alvaro, D., Andreone, P., Andriulli, A., Azzaroli, F., Battezzati, P. M., Benedetti, A., Bragazzi, M., Brunetto, M., Bruno, S., Calvaruso, V., Cardinale, V., Casella, G., Cazzagon, N., Ciaccio, A., Coco, B., Colli, A., Colloredo, G., Colombo, M., Colombo, S., Cristoferi, L., Cursaro, C., Croce, L. S., Crosignani, A., D'Amato, D., Donato, F., Elia, G., Fabris, L., Fagiuoli, S., Ferrari, C., Floreani, A., Galli, A., Giannini, E., Grattagliano, I., Lampertico, P., Lleo, A., Malinverno, F., Mancuso, C., Marra, F., Marzioni, M., Massironi, S., Mattalia, A., Miele, L., Milani, C., Morini, L., Morisco, F., Muratori, L., Muratori, P., Niro, G. A., O'Donnell, S., Picciotto, A., Portincasa, P., Rigamonti, C., Ronca, V., Rosina, F., Spinzi, G., Strazzabosco, M., Tarocchi, M., Tiribelli, C., Toniutto, P., Valenti, L., Vinci, M., Zuin, M., Nakamura, H., Abiru, S., Nagaoka, S., Komori, A., Yatsuhashi, H., Ishibashi, H., Ito, M., Migita, K., Ohira, H., Katsushima, S., Naganuma, A., Sugi, K., Komatsu, T., Mannami, T., Matsushita, K., Yoshizawa, K., Makita, F., Nikami, T., Nishimura, H., Kouno, H., Ota, H., Komura, T., Nakamura, Y., Shimada, M., Hirashima, N., Komeda, T., Ario, K., Nakamuta, M., Yamashita, T., Furuta, K., Kikuchi, M., Naeshiro, N., Takahashi, H., Mano, Y., Tsunematsu, S., Yabuuchi, I., Shimada, Y., Yamauchi, K., Sugimoto, R., Sakai, H., Mita, E., Koda, M., Tsuruta, S., Kamitsukasa, H., Sato, T., Masaki, N., Kobata, T., Fukushima, N., Ohara, Y., Muro, T., Takesaki, E., Takaki, H., Yamamoto, T., Kato, M., Nagaoki, Y., Hayashi, S., Ishida, J., Watanabe, Y., Kobayashi, M., Koga, M., Saoshiro, T., Yagura, M., Hirata, K., Tanaka, A., Takikawa, H., Zeniya, M., Abe, M., Onji, M., Kaneko, S., Honda, M., Arai, K., Arinaga-Hino, T., Hashimoto, E., Taniai, M., Umemura, T., Joshita, S., Nakao, K., Ichikawa, T., Shibata, H., Yamagiwa, S., Seike, M., Honda, K., Sakisaka, S., Takeyama, Y., Harada, M., Senju, M., Yokosuka, O., Kanda, T., Ueno, Y., Kikuchi, K., Ebinuma, H., Himoto, T., Yasunami, M., Murata, K., Mizokami, M., Kawata, K., Shimoda, S., Miyake, Y., Takaki, A., Yamamoto, K., Hirano, K., Ichida, T., Ido, A., Tsubouchi, H., Chayama, K., Harada, K., Nakanuma, Y., Maehara, Y., Taketomi, A., Shirabe, K., Soejima, Y., Mori, A., Yagi, S., Uemoto, S., H, E., Tanaka, T., Yamashiki, N., Tamura, S., Sugawara, Y., Kokudo, N., Chalasani, N., Luketic, V., Odin, J., Chopra, K., Abecasis, G., Cantor, M., Coppola, G., Economides, A., Lotta, L. A., Overton, J. D., Reid, J. G., Shuldiner, A., Beechert, C., Forsythe, C., Fuller, E. D., Gu, Z., Lattari, M., Lopez, A., Schleicher, T. D., Padilla, M. S., Toledo, K., Widom, L., Wolf, S. E., Pradhan, M., Manoochehri, K., Ulloa, R. H., Bai, X., Balasubramanian, S., Barnard, L., Blumenfeld, A., Eom, G., Habegger, L., Hawes, A., Khalid, S., Maxwell, E. K., Salerno, W., Staples, J. C., Jones, M. B., Mitnaul, L. J., Sturgess, R., Healey, C., Yeoman, A., Gunasekera, A. V., Kooner, P., Kapur, K., Sathyanarayana, V., Kallis, Y., Subhani, J., Harvey, R., Mccorry, R., Rooney, P., Ramanaden, D., Evans, R., Mathialahan, T., Gasem, J., Shorrock, C., Bhalme, M., Southern, P., Tibble, J. A., Gorard, D. A., Jones, S., Mells, G., Mulcahy, V., Srivastava, B., Foxton, M. R., Collins, C. E., Elphick, D., Karmo, M., Porras-Perez, F., Mendall, M., Yapp, T., Patel, M., Ede, R., Sayer, J., Jupp, J., Fisher, N., Carter, M. J., Koss, K., Shah, J., Piotrowicz, A., Scott, G., Grimley, C., Gooding, I. R., Williams, S., Tidbury, J., Lim, G., Cheent, K., Levi, S., Mansour, D., Beckley, M., Hollywood, C., Wong, T., Marley, R., Ramage, J., Gordon, H. M., Ridpath, J., Ngatchu, T., Bob Grover, V. P., Shidrawi, R. G., Abouda, G., Corless, L., Narain, M., Rees, I., Brown, A., Taylor-Robinson, S., Wilkins, J., Grellier, L., Banim, P., Das, D., Heneghan, M. A., Curtis, H., Matthews, H. C., Mohammed, F., Aldersley, M., Srirajaskanthan, R., Walker, G., Mcnair, A., Sharif, A., Sen, S., Bird, G., Prince, M. I., Prasad, G., Kitchen, P., Barnardo, A., Oza, C., Sivaramakrishnan, N. N., Gupta, P., Shah, A., Evans, C. D., Saha, S., Pollock, K., Bramley, P., Mukhopadhya, A., Barclay, S. T., Mcdonald, N., Bathgate, A. J., Palmer, K., Dillon, J. F., Rushbrook, S. M., Przemioslo, R., Mcdonald, C., Millar, A., Tai, C., Mitchell, S., Metcalf, J., Shaukat, S., Ninkovic, M., Shmueli, U., Davis, A., Naqvi, A., Lee, T. J., Ryder, S., Collier, J., Klass, H., Cramp, M. E., Sharer, N., Aspinall, R., Ghosh, D., Douds, A. C., Booth, J., Williams, E., Hussaini, H., Christie, J., Mann, S., Thorburn, D., Marshall, A., Patanwala, I., Ala, A., Maltby, J., Matthew, R., Corbett, C., Vyas, S., Singhal, S., Gleeson, D., Misra, S., Butterworth, J., George, K., Harding, T., Douglass, A., Mitchison, H., Panter, S., Shearman, J., Bray, G., Roberts, M., Butcher, G., Forton, D., Mahmood, Z., Cowan, M., Ch'Ng, C. L., Rahman, M., Whatley, G. C. A., Wesley, E., Mandal, A., Jain, S., Pereira, S. P., Wright, M., Trivedi, P., Gordon, F. H., Unitt, E., Palejwala, A., Austin, A., Vemala, V., Grant, A., Higham, A. D., Brind, A., Mathew, R., Cox, M., Ramakrishnan, S., King, A., Whalley, S., Fraser, J., Thomson, S. J., Bell, A., Wong, V. S., Kia, R., Gee, I., Keld, R., Ransford, R., Gotto, J., Millson, C., Cordell H.J., Fryett J.J., Ueno K., Darlay R., Aiba Y., Hitomi Y., Kawashima M., Nishida N., Khor S.-S., Gervais O., Kawai Y., Nagasaki M., Tokunaga K., Tang R., Shi Y., Li Z., Juran B.D., Atkinson E.J., Gerussi A., Carbone M., Asselta R., Cheung A., de Andrade M., Baras A., Horowitz J., Ferreira M.A.R., Sun D., Jones D.E., Flack S., Spicer A., Mulcahy V.L., Byan J., Han Y., Sandford R.N., Lazaridis K.N., Amos C.I., Hirschfield G.M., Seldin M.F., Invernizzi P., Siminovitch K.A., Ma X., Nakamura M., Mells G.F., Mason A., Vincent C., Xie G., Zhang J., Affronti A., Almasio P.L., Alvaro D., Andreone P., Andriulli A., Azzaroli F., Battezzati P.M., Benedetti A., Bragazzi M., Brunetto M., Bruno S., Calvaruso V., Cardinale V., Casella G., Cazzagon N., Ciaccio A., Coco B., Colli A., Colloredo G., Colombo M., Colombo S., Cristoferi L., Cursaro C., Croce L.S., Crosignani A., D'Amato D., Donato F., Elia G., Fabris L., Fagiuoli S., Ferrari C., Floreani A., Galli A., Giannini E., Grattagliano I., Lampertico P., Lleo A., Malinverno F., Mancuso C., Marra F., Marzioni M., Massironi S., Mattalia A., Miele L., Milani C., Morini L., Morisco F., Muratori L., Muratori P., Niro G.A., O'Donnell S., Picciotto A., Portincasa P., Rigamonti C., Ronca V., Rosina F., Spinzi G., Strazzabosco M., Tarocchi M., Tiribelli C., Toniutto P., Valenti L., Vinci M., Zuin M., Nakamura H., Abiru S., Nagaoka S., Komori A., Yatsuhashi H., Ishibashi H., Ito M., Migita K., Ohira H., Katsushima S., Naganuma A., Sugi K., Komatsu T., Mannami T., Matsushita K., Yoshizawa K., Makita F., Nikami T., Nishimura H., Kouno H., Ota H., Komura T., Nakamura Y., Shimada M., Hirashima N., Komeda T., Ario K., Nakamuta M., Yamashita T., Furuta K., Kikuchi M., Naeshiro N., Takahashi H., Mano Y., Tsunematsu S., Yabuuchi I., Shimada Y., Yamauchi K., Sugimoto R., Sakai H., Mita E., Koda M., Tsuruta S., Kamitsukasa H., Sato T., Masaki N., Kobata T., Fukushima N., Ohara Y., Muro T., Takesaki E., Takaki H., Yamamoto T., Kato M., Nagaoki Y., Hayashi S., Ishida J., Watanabe Y., Kobayashi M., Koga M., Saoshiro T., Yagura M., Hirata K., Tanaka A., Takikawa H., Zeniya M., Abe M., Onji M., Kaneko S., Honda M., Arai K., Arinaga-Hino T., Hashimoto E., Taniai M., Umemura T., Joshita S., Nakao K., Ichikawa T., Shibata H., Yamagiwa S., Seike M., Honda K., Sakisaka S., Takeyama Y., Harada M., Senju M., Yokosuka O., Kanda T., Ueno Y., Kikuchi K., Ebinuma H., Himoto T., Yasunami M., Murata K., Mizokami M., Kawata K., Shimoda S., Miyake Y., Takaki A., Yamamoto K., Hirano K., Ichida T., Ido A., Tsubouchi H., Chayama K., Harada K., Nakanuma Y., Maehara Y., Taketomi A., Shirabe K., Soejima Y., Mori A., Yagi S., Uemoto S., H E., Tanaka T., Yamashiki N., Tamura S., Sugawara Y., Kokudo N., Chalasani N., Luketic V., Odin J., Chopra K., Abecasis G., Cantor M., Coppola G., Economides A., Lotta L.A., Overton J.D., Reid J.G., Shuldiner A., Beechert C., Forsythe C., Fuller E.D., Gu Z., Lattari M., Lopez A., Schleicher T.D., Padilla M.S., Toledo K., Widom L., Wolf S.E., Pradhan M., Manoochehri K., Ulloa R.H., Bai X., Balasubramanian S., Barnard L., Blumenfeld A., Eom G., Habegger L., Hawes A., Khalid S., Maxwell E.K., Salerno W., Staples J.C., Jones M.B., Mitnaul L.J., Sturgess R., Healey C., Yeoman A., Gunasekera A.V., Kooner P., Kapur K., Sathyanarayana V., Kallis Y., Subhani J., Harvey R., McCorry R., Rooney P., Ramanaden D., Evans R., Mathialahan T., Gasem J., Shorrock C., Bhalme M., Southern P., Tibble J.A., Gorard D.A., Jones S., Mells G., Mulcahy V., Srivastava B., Foxton M.R., Collins C.E., Elphick D., Karmo M., Porras-Perez F., Mendall M., Yapp T., Patel M., Ede R., Sayer J., Jupp J., Fisher N., Carter M.J., Koss K., Shah J., Piotrowicz A., Scott G., Grimley C., Gooding I.R., Williams S., Tidbury J., Lim G., Cheent K., Levi S., Mansour D., Beckley M., Hollywood C., Wong T., Marley R., Ramage J., Gordon H.M., Ridpath J., Ngatchu T., Bob Grover V.P., Shidrawi R.G., Abouda G., Corless L., Narain M., Rees I., Brown A., Taylor-Robinson S., Wilkins J., Grellier L., Banim P., Das D., Heneghan M.A., Curtis H., Matthews H.C., Mohammed F., Aldersley M., Srirajaskanthan R., Walker G., McNair A., Sharif A., Sen S., Bird G., Prince M.I., Prasad G., Kitchen P., Barnardo A., Oza C., Sivaramakrishnan N.N., Gupta P., Shah A., Evans C.D., Saha S., Pollock K., Bramley P., Mukhopadhya A., Barclay S.T., McDonald N., Bathgate A.J., Palmer K., Dillon J.F., Rushbrook S.M., Przemioslo R., McDonald C., Millar A., Tai C., Mitchell S., Metcalf J., Shaukat S., Ninkovic M., Shmueli U., Davis A., Naqvi A., Lee T.J., Ryder S., Collier J., Klass H., Cramp M.E., Sharer N., Aspinall R., Ghosh D., Douds A.C., Booth J., Williams E., Hussaini H., Christie J., Mann S., Thorburn D., Marshall A., Patanwala I., Ala A., Maltby J., Matthew R., Corbett C., Vyas S., Singhal S., Gleeson D., Misra S., Butterworth J., George K., Harding T., Douglass A., Mitchison H., Panter S., Shearman J., Bray G., Roberts M., Butcher G., Forton D., Mahmood Z., Cowan M., Ch'ng C.L., Rahman M., Whatley G.C.A., Wesley E., Mandal A., Jain S., Pereira S.P., Wright M., Trivedi P., Gordon F.H., Unitt E., Palejwala A., Austin A., Vemala V., Grant A., Higham A.D., Brind A., Mathew R., Cox M., Ramakrishnan S., King A., Whalley S., Fraser J., Thomson S.J., Bell A., Wong V.S., Kia R., Gee I., Keld R., Ransford R., Gotto J., Millson C., Medical Research Council (MRC), LiveR North, Cordell, H, Fryett, J, Ueno, K, Darlay, R, Aiba, Y, Hitomi, Y, Kawashima, M, Nishida, N, Khor, S, Gervais, O, Kawai, Y, Nagasaki, M, Tokunaga, K, Tang, R, Shi, Y, Li, Z, Juran, B, Atkinson, E, Gerussi, A, Carbone, M, Asselta, R, Cheung, A, de Andrade, M, Baras, A, Horowitz, J, Ferreira, M, Sun, D, Jones, D, Flack, S, Spicer, A, Mulcahy, V, Byan, J, Han, Y, Sandford, R, Lazaridis, K, Amos, C, Hirschfield, G, Seldin, M, Invernizzi, P, Siminovitch, K, Ma, X, Nakamura, M, Mells, G, Mason, A, Vincent, C, Xie, G, Zhang, J, Affronti, A, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Azzaroli, F, Battezzati, P, Benedetti, A, Bragazzi, M, Brunetto, M, Bruno, S, Calvaruso, V, Cardinale, V, Casella, G, Cazzagon, N, Ciaccio, A, Coco, B, Colli, A, Colloredo, G, Colombo, M, Colombo, S, Cristoferi, L, Cursaro, C, Croce, L, Crosignani, A, D'Amato, D, Donato, F, Elia, G, Fabris, L, Fagiuoli, S, Ferrari, C, Floreani, A, Galli, A, Giannini, E, Grattagliano, I, Lampertico, P, Lleo, A, Malinverno, F, Mancuso, C, Marra, F, Marzioni, M, Massironi, S, Mattalia, A, Miele, L, Milani, C, Morini, L, Morisco, F, Muratori, L, Muratori, P, Niro, G, O'Donnell, S, Picciotto, A, Portincasa, P, Rigamonti, C, Ronca, V, Rosina, F, Spinzi, G, Strazzabosco, M, Tarocchi, M, Tiribelli, C, Toniutto, P, Valenti, L, Vinci, M, Zuin, M, Nakamura, H, Abiru, S, Nagaoka, S, Komori, A, Yatsuhashi, H, Ishibashi, H, Ito, M, Migita, K, Ohira, H, Katsushima, S, Naganuma, A, Sugi, K, Komatsu, T, Mannami, T, Matsushita, K, Yoshizawa, K, Makita, F, Nikami, T, Nishimura, H, Kouno, H, Ota, H, Komura, T, Nakamura, Y, Shimada, M, Hirashima, N, Komeda, T, Ario, K, Nakamuta, M, Yamashita, T, Furuta, K, Kikuchi, M, Naeshiro, N, Takahashi, H, Mano, Y, Tsunematsu, S, Yabuuchi, I, Shimada, Y, Yamauchi, K, Sugimoto, R, Sakai, H, Mita, E, Koda, M, Tsuruta, S, Kamitsukasa, H, Sato, T, Masaki, N, Kobata, T, Fukushima, N, Ohara, Y, Muro, T, Takesaki, E, Takaki, H, Yamamoto, T, Kato, M, Nagaoki, Y, Hayashi, S, Ishida, J, Watanabe, Y, Kobayashi, M, Koga, M, Saoshiro, T, Yagura, M, Hirata, K, Tanaka, A, Takikawa, H, Zeniya, M, Abe, M, Onji, M, Kaneko, S, Honda, M, Arai, K, Arinaga-Hino, T, Hashimoto, E, Taniai, M, Umemura, T, Joshita, S, Nakao, K, Ichikawa, T, Shibata, H, Yamagiwa, S, Seike, M, Honda, K, Sakisaka, S, Takeyama, Y, Harada, M, Senju, M, Yokosuka, O, Kanda, T, Ueno, Y, Kikuchi, K, Ebinuma, H, Himoto, T, Yasunami, M, Murata, K, Mizokami, M, Kawata, K, Shimoda, S, Miyake, Y, Takaki, A, Yamamoto, K, Hirano, K, Ichida, T, Ido, A, Tsubouchi, H, Chayama, K, Harada, K, Nakanuma, Y, Maehara, Y, Taketomi, A, Shirabe, K, Soejima, Y, Mori, A, Yagi, S, Uemoto, S, H, E, Tanaka, T, Yamashiki, N, Tamura, S, Sugawara, Y, Kokudo, N, Chalasani, N, Luketic, V, Odin, J, Chopra, K, Abecasis, G, Cantor, M, Coppola, G, Economides, A, Lotta, L, Overton, J, Reid, J, Shuldiner, A, Beechert, C, Forsythe, C, Fuller, E, Gu, Z, Lattari, M, Lopez, A, Schleicher, T, Padilla, M, Toledo, K, Widom, L, Wolf, S, Pradhan, M, Manoochehri, K, Ulloa, R, Bai, X, Balasubramanian, S, Barnard, L, Blumenfeld, A, Eom, G, Habegger, L, Hawes, A, Khalid, S, Maxwell, E, Salerno, W, Staples, J, Jones, M, Mitnaul, L, Sturgess, R, Healey, C, Yeoman, A, Gunasekera, A, Kooner, P, Kapur, K, Sathyanarayana, V, Kallis, Y, Subhani, J, Harvey, R, Mccorry, R, Rooney, P, Ramanaden, D, Evans, R, Mathialahan, T, Gasem, J, Shorrock, C, Bhalme, M, Southern, P, Tibble, J, Gorard, D, Jones, S, Srivastava, B, Foxton, M, Collins, C, Elphick, D, Karmo, M, Porras-Perez, F, Mendall, M, Yapp, T, Patel, M, Ede, R, Sayer, J, Jupp, J, Fisher, N, Carter, M, Koss, K, Shah, J, Piotrowicz, A, Scott, G, Grimley, C, Gooding, I, Williams, S, Tidbury, J, Lim, G, Cheent, K, Levi, S, Mansour, D, Beckley, M, Hollywood, C, Wong, T, Marley, R, Ramage, J, Gordon, H, Ridpath, J, Ngatchu, T, Bob Grover, V, Shidrawi, R, Abouda, G, Corless, L, Narain, M, Rees, I, Brown, A, Taylor-Robinson, S, Wilkins, J, Grellier, L, Banim, P, Das, D, Heneghan, M, Curtis, H, Matthews, H, Mohammed, F, Aldersley, M, Srirajaskanthan, R, Walker, G, Mcnair, A, Sharif, A, Sen, S, Bird, G, Prince, M, Prasad, G, Kitchen, P, Barnardo, A, Oza, C, Sivaramakrishnan, N, Gupta, P, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Barclay, S, Mcdonald, N, Bathgate, A, Palmer, K, Dillon, J, Rushbrook, S, Przemioslo, R, Mcdonald, C, Millar, A, Tai, C, Mitchell, S, Metcalf, J, Shaukat, S, Ninkovic, M, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Klass, H, Cramp, M, Sharer, N, Aspinall, R, Ghosh, D, Douds, A, Booth, J, Williams, E, Hussaini, H, Christie, J, Mann, S, Thorburn, D, Marshall, A, Patanwala, I, Ala, A, Maltby, J, Matthew, R, Corbett, C, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Mitchison, H, Panter, S, Shearman, J, Bray, G, Roberts, M, Butcher, G, Forton, D, Mahmood, Z, Cowan, M, Ch'Ng, C, Rahman, M, Whatley, G, Wesley, E, Mandal, A, Jain, S, Pereira, S, Wright, M, Trivedi, P, Gordon, F, Unitt, E, Palejwala, A, Austin, A, Vemala, V, Grant, A, Higham, A, Brind, A, Mathew, R, Cox, M, Ramakrishnan, S, King, A, Whalley, S, Fraser, J, Thomson, S, Bell, A, Wong, V, Kia, R, Gee, I, Keld, R, Ransford, R, Gotto, J, Millson, C, Cordell HJ, Fryett JJ, Ueno K, Darlay R, Aiba Y, Hitomi Y, Kawashima M, Nishida N, Khor SS, Gervais O, Kawai Y, Nagasaki M, Tokunaga K, Tang R, Shi Y, Li Z, Juran BD, Atkinson EJ, Gerussi A, Carbone M, Asselta R, Cheung A, de Andrade M, Baras A, Horowitz J, Ferreira MAR, Sun D, Jones DE, Flack S, Spicer A, Mulcahy VL, Byan J, Han Y, Sandford RN, Lazaridis KN, Amos CI, Hirschfield GM, Seldin MF, Invernizzi P, Siminovitch KA, Ma X, Nakamura M, Mells GF, PBC Consortia, Canadian PBC Consortium, Chinese PBC Consortium, Italian PBC Study Group, Japan-PBC-GWAS Consortium, US PBC Consortium, UK-PBC Consortium, and Calvaruso V. .
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Liver Cirrhosis ,ALSPAC ,ERN RARE-LIVER ,Genomic co-localization ,Network-based in silico drug efficacy screening ,UK-PBC ,0301 basic medicine ,Candidate gene ,Genome-Wide Association Study ,Humans ,Liver Cirrhosis, Biliary ,Italian PBC Study Group ,LD SCORE REGRESSION ,Japan-PBC-GWAS Consortium ,Genome-wide association study ,Locus (genetics) ,Disease ,SUSCEPTIBILITY ,PBC ,Chronic liver disease ,Bioinformatics ,GENETIC ASSOCIATION ,1117 Public Health and Health Services ,03 medical and health sciences ,0302 clinical medicine ,UK-PBC Consortium ,Genotype ,Medicine ,Genetic association ,Science & Technology ,Gastroenterology & Hepatology ,Hepatology ,business.industry ,Biliary ,Chinese PBC Consortium ,1103 Clinical Sciences ,medicine.disease ,PBC Consortia ,030104 developmental biology ,Meta-analysis ,ERN RARE LIVER ,030211 gastroenterology & hepatology ,US PBC Consortium ,Canadian PBC Consortium ,business ,Life Sciences & Biomedicine ,Human - Abstract
[BACKGROUND & AIMS] Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intra-hepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. [METHODS] We combined new and existing genotype data for 10, 516 cases and 20, 772 controls from five European and two East Asian cohorts. [RESULTS] We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, each having key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, Jak-STAT signalling, and differentiation of TH1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some well-established in the treatment of other autoimmune disorders. [CONCLUSIONS] This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. [Lay summary] Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10, 516 people with PBC and 20, 772 healthy individuals recruited in Canada, China, Italy, Japan, UK, or USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these ‘candidate genes’ to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC., 原発性胆汁性胆管炎のゲノムワイド関連解析 --国際メタ解析による新規疾患感受性遺伝子と治療薬候補の同定--. 京都大学プレスリリース. 2021-06-28.
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- 2021
37. Giant Hepatic Hemangioma Causing Prolonged Fever and Indicated for Resection.
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Chihiro Yoshimizu, Shunichi Ariizumi, Tomomi Kogiso, Takaomi Sagawa, Makiko Taniai, Goro Honda, Hiroto Egawa, and Katsutoshi Tokushige
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- 2022
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38. The transition in the etiologies of hepatocellular carcinoma-complicated liver cirrhosis in a nationwide survey of Japan
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Hiroki Nishikawa, Hirayuki Enomoto, Shuhei Hige, Kohichiroh Yasui, Akio Ido, Yoichi Hiasa, Masayuki Kurosaki, Yoshiyuki Ueno, Shuhei Nishiguchi, Koichi Takaguchi, Makiko Taniai, Tatsuya Kanto, Toru Ishikawa, Yasuhiro Takikawa, and Akinobu Takaki
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Liver Cirrhosis ,Male ,medicine.medical_specialty ,Alcoholic liver disease ,Cirrhosis ,Carcinoma, Hepatocellular ,Etiology ,Hepatocellular carcinoma ,Hepatitis C virus ,medicine.disease_cause ,Gastroenterology ,Japan ,Internal medicine ,Surveys and Questionnaires ,Medicine ,Humans ,neoplasms ,Liver Diseases, Alcoholic ,Aged ,Hepatitis B virus ,Original Article—Liver, Pancreas, and Biliary Tract ,business.industry ,Incidence (epidemiology) ,Incidence ,Liver Neoplasms ,Hepatology ,Middle Aged ,medicine.disease ,Hepatitis B ,Hepatitis C ,digestive system diseases ,Female ,business ,Viral hepatitis ,Nationwide survey - Abstract
Background We recently reported the real-world changes in the etiologies of liver cirrhosis (LC) based on nationwide survey data and assessed the etiologies of LC with hepatocellular carcinoma (HCC). Methods Fifty-five participants from 68 institutions provided data on 23,637 patients with HCC-complicated LC. The changing trends in etiologies were assessed. We further analyzed the data from 29 hospitals that provided the annual number of newly identified HCC-complicated LC patients from 2008 to 2016 (N = 9362) without any missing years and assessed the transition in the real number of newly identified HCC-complicated LC cases. Results In the overall cohort, hepatitis C virus (HCV) infection (60.3%) and hepatitis B virus (HBV) infection (12.9%) were the leading and third-most common causes of HCC-complicated LC in Japan, respectively. HCV infection was found to be the leading cause throughout Japan. The rate of viral hepatitis-related HCC decreased from 85.3 to 64.4%. Among non-viral etiologies, notable increases were observed in nonalcoholic steatohepatitis (NASH)-related HCC (from 1.5 to 7.2%) and alcoholic liver disease (ALD)-related HCC (from 8.5 to 18.6%). Regarding the real number of newly diagnosed patients, the number of patients with viral hepatitis-related HCC decreased, while the number of patients with non-viral HCC, particularly NASH-related HCC, increased. Conclusions Viral hepatitis has remained the main cause of HCC in Japan. However, the decrease in viral hepatitis-related HCC, particularly HCV-related HCC highly contributed to the etiological changes. In addition, the increased incidence of non-viral HCC, particularly NASH-related HCC, was involved in the changing etiologies of HCC-complicated LC in Japan.
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- 2020
39. Outcomes of Japanese patients with non-alcoholic fatty liver disease according to genetic background and lifestyle-related diseases
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Tomomi Kogiso, Takaomi Sagawa, Etsuko Hashimoto, Makiko Taniai, Katsutoshi Tokushige, and Kazuhisa Kodama
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Adult ,Male ,medicine.medical_specialty ,Patatin-like phospholipase 3 (PNPLA3) ,Adolescent ,Genotype ,Biopsy ,Specialties of internal medicine ,Single-nucleotide polymorphism ,Subgroup analysis ,Disease ,Gastroenterology ,Polymorphism, Single Nucleotide ,Non-alcoholic fatty liver disease (NAFLD) ,Young Adult ,Japan ,Single nucleotide polymorphism (SNP) ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,medicine ,Humans ,Mortality ,Life Style ,ALDH2 ,Aged ,Aldehyde dehydrogenase 2 (ALDH2) ,Aged, 80 and over ,Hepatology ,medicine.diagnostic_test ,business.industry ,Aldehyde Dehydrogenase, Mitochondrial ,Hazard ratio ,Fatty liver ,General Medicine ,DNA ,Middle Aged ,medicine.disease ,RC581-951 ,Hepatocellular carcinoma ,Female ,Liver function tests ,business ,Genetic Background - Abstract
Introduction and objectives Genetic background may be involved in the mechanisms of liver injury and the development of non-alcoholic fatty liver disease (NAFLD). However, its contributions to the long-term outcome of NAFLD have been unclear. Methods We enrolled 314 Japanese patients with biopsy-confirmed NAFLD from 2000 to 2018 (161 men [51.3%]; median age, 53 [14–84] years; 114 with advanced fibrosis [37.5%]) in the patients without hepatocellular carcinoma at diagnosis. Genomic DNA was extracted from peripheral blood and single nucleotide polymorphisms (SNPs) were analyzed. Associations of mortality with patatin-like phospholipase 3 (PNPLA3) and aldehyde dehydrogenase 2 (ALDH2) were analyzed. Finally, a subgroup analysis according to lifestyle-related disease was performed. Results During the median 7 years of follow-up, 20 patients (6.4%) died (13 liver-related [4.1%] and 7 non-liver-related deaths [2.2%]). Patients with ALDH2 (non-GG genotype) who had reduced alcohol metabolism tended to have a poor prognosis (p = 0.06). Patients carrying both risk SNPs of PNPLA3 (GG) and ALDH2 (non-GG) had a significantly poor prognosis (p = 0.01). In the subgroup analysis, patients with PNPLA3 (GG) who were non-diabetics (p = 0.06) or non-dyslipidemic (p = 0.03), with ALDH2 (non-GG) who were non-dyslipidemic (p = 0.01) or hypertensive (p = 0.03), also had a poor prognosis. The Cox analysis revealed that ALDH2 (non-GG) was associated with a poor prognosis (Hazard ratio: 4.568, 95% Confidence Interval: 1.294–16.131, p = 0.02) similar to the liver function tests. Conclusions Genetic background may affect NAFLD prognosis and ALDH2 SNP could predict the outcome.
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- 2020
40. Development and course of diabetes according to genetic factors and diabetes treatment among patients with nonalcoholic fatty liver disease
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Katsutoshi Tokushige, Kazuhisa Kodama, Tomomi Kogiso, Makiko Taniai, Etsuko Hashimoto, and Takaomi Sagawa
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0301 basic medicine ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Incretin ,030209 endocrinology & metabolism ,Single-nucleotide polymorphism ,Gastroenterology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Diabetes mellitus ,Nonalcoholic fatty liver disease ,Genotype ,Medicine ,Humans ,Genetic Predisposition to Disease ,Sodium-Glucose Cotransporter 2 Inhibitor ,Sodium-Glucose Transporter 2 Inhibitors ,030109 nutrition & dietetics ,Nutrition and Dietetics ,business.industry ,Incidence (epidemiology) ,Insulin ,Membrane Proteins ,Lipase ,medicine.disease ,Diabetes Mellitus, Type 2 ,business - Abstract
Many patients with nonalcoholic fatty liver disease (NAFLD) also have diabetes. However, the genetic factors associated with diabetes in NAFLD are unclear. In this study, we investigated the clinical course and risk factors of diabetes development.A total of 544 patients (275 men; 50.6%) with a median age of 53 y and biopsy-confirmed NAFLD enrolled in the study. Patatin-like phospholipase 3 and voltage-gated potassium channel KQT-like subfamily member 1 (KCNQ1) single nucleotide polymorphisms were identified in 287 cases. There were 272 patients without diabetes, and 64, 141, and 67 patients with diabetes not treated with an oral hypoglycemic agent, treated with an oral hypoglycemic agent, and treated with insulin, respectively. Changes in biochemical parameters and body weight over a 1-y period were determined in patients treated with incretin agents (n = 91), a sodium glucose cotransporter 2 inhibitor (n = 19), or both (n = 33). The prevalence and risk factors for diabetes development among patients with NAFLD were determined in nondiabetic patients.Among patients with NAFLD, half of the patients had diabetes and the incidence was high in those with advanced fibrosis. Reduction in body weight was higher after sodium glucose cotransporter 2 inhibitor treatment (P = .050) and in KCNQ1 CC genotype patients (P.05). Reduction in hemoglobin A1c level was significantly lower in patatin-like phospholipase 3 GG subjects (P.05). De novo diabetes developed in 44 patients (10-y incidence: 17.9%), especially in obese (P = .046) and KCNQ1 CC genotype patients (P.01).Patient genetic background affected treatment response and incidence of diabetes in patients with NAFLD.
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- 2020
41. Hepatocellular carcinoma in young morbid obese patients with non-alcoholic fatty liver disease
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Takayoshi Nishino, Katsutoshi Tokushige, Etsuko Hashimoto, Makiko Taniai, and Maki Tobari
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Adult ,Male ,medicine.medical_specialty ,Liver tumor ,Carcinoma, Hepatocellular ,Gastroenterology ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Weight loss ,Fibrosis ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Biomarkers, Tumor ,Medicine ,Humans ,Protein Precursors ,business.industry ,Fatty liver ,Liver Neoplasms ,General Medicine ,Hepatology ,medicine.disease ,digestive system diseases ,Obesity, Morbid ,Blood chemistry ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,030211 gastroenterology & hepatology ,Prothrombin ,alpha-Fetoproteins ,medicine.symptom ,Steatohepatitis ,business ,Biomarkers - Abstract
We report the two youngest cases of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) among our 119 NAFLD-HCC patients. A 36-year-old man was referred to our hospital due to a 5 cm in diameter liver tumor with elevation of α-fetoprotein and des-γ-carboxy prothrombin found at his annual health check. He had no symptoms other than 20 kg weight loss. He has been morbidly obese since he was a child. At the time of the diagnosis of NAFLD-HCC, blood chemistry showed FIB4-index 0.52, α-fetoprotein 11.1 ng/mL and des-γ-carboxy prothrombin 361 mAU/mL. He underwent curative operation. The non-cancerous lesion showed steatohepatitis with mild fibrosis. A 41-year-old man was diagnosed as having a huge liver tumor (15 cm in diameter) during medical examination for 10 kg weight loss. He had no clinical symptoms except weight loss. He has been morbidly obese since childhood. NAFLD was diagnosed at age 20. At the time of the HCC diagnosis, blood chemistry showed FIB4-index 1.42, α-fetoprotein 1974 ng/mL, and des-γ-carboxy prothrombin 82,602 mAU/mL. He underwent curative operation. We have to be aware that HCC can develop in young NAFLD patients without advanced fibrosis. Concerning tumor markers, elevation of des-γ-carboxy prothrombin was more sensitive than α-fetoprotein.
- Published
- 2020
42. The current status of alcohol liver disease
- Author
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Makiko Taniai
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Alcohol ,medicine.disease ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,Liver disease ,0302 clinical medicine ,chemistry ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,030211 gastroenterology & hepatology ,Current (fluid) ,business - Published
- 2018
43. Risk factors for recurrence of primary biliary cholangitis after liver transplantation in female patients: A Japanese multicenter retrospective study
- Author
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Satomi Sakabayashi, Hiroto Egawa, Tomomi Kogiso, Katsutoshi Tokushige, Shotaro Sakisaka, Koji Umeshita, Masakazu Yamamoto, Satoshi Teramukai, Makiko Taniai, Shinji Uemoto, and Etsuko Hashimoto
- Subjects
medicine.medical_specialty ,Framingham Risk Score ,Hepatology ,business.industry ,medicine.medical_treatment ,Hazard ratio ,Retrospective cohort study ,Original Articles ,030230 surgery ,Liver transplantation ,medicine.disease ,Gastroenterology ,Confidence interval ,Surgery ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Internal medicine ,Female patient ,medicine ,Original Article ,030211 gastroenterology & hepatology ,business - Abstract
Primary biliary cholangitis (PBC) is diagnosed mainly in female individuals, and risk factors for PBC recurrence (rPBC) after liver transplantation (LT) from cadaveric donors have been reported. We conducted a retrospective multicenter study of rPBC in female patients after living-donor LT (LDLT). A total of 388 female patients undergoing LDLT for end-stage PBC were enrolled, and the effects of preoperative and operative factors were evaluated. Postoperative factors were evaluated in 312 patients who survived for more than 1 year post-LDLT. rPBC was defined as abnormal hepatic enzyme levels with typical histological findings in liver biopsies. Fifty-eight patients (14.9%) developed rPBC with a median of 4.6 (0.8-14.5) years post-LT. Cox hazard analysis (P < 0.05) showed that younger recipient age (hazard ratio, 0.95; 95% confidence interval, 0.920-0.982), shorter operative time (1.00; 0.995-0.999), higher serum immunoglobulin M level (1.00; 1.001-1.002), donor sex mismatch (2.45; 1.268-4.736), human leukocyte antigen B60 (2.56; 1.336-4.921) and DR8 (1.98; 1.134-3.448), and initial treatment with cyclosporine A (3.14; 1.602-6.138) were significantly associated with rPBC. The frequencies of Child-Turcotte-Pugh class C (0.46; 0.274-0.775), the model of end-stage liver disease score (0.96; 0.914-0.998), and updated Mayo risk score (1.02; 1.005-1.033) were significantly lower in rPBC. Posttransplantation use of steroids decreased and that of antimetabolites increased the frequency of rPBC. Conclusion: The timing of LT, recipient conditions, donor characteristics, and immunosuppressive medications may be associated with rPBC in LT recipients. (Hepatology Communications 2017;1:394-405).
- Published
- 2017
44. The Outcome of Cirrhotic Patients with Ascites Is Improved by the Normalization of the Serum Sodium Level by Tolvaptan
- Author
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Kuniko Yamamoto, Nobuyuki Torii, Katsutoshi Tokushige, Tomomi Kogiso, Mutsuki Kobayashi, Yuichi Ikarashi, Kazuhisa Kodama, Etsuko Hashimoto, and Makiko Taniai
- Subjects
Liver Cirrhosis ,Male ,medicine.medical_specialty ,Cirrhosis ,hyponatremia ,Tolvaptan ,030204 cardiovascular system & hematology ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Japan ,brain natriuretic peptide (BNP) ,Internal medicine ,Ascites ,Internal Medicine ,medicine ,Humans ,Survival rate ,Aged ,Retrospective Studies ,tolvaptan ,business.industry ,Sodium ,General Medicine ,Odds ratio ,Benzazepines ,Middle Aged ,Prognosis ,medicine.disease ,Brain natriuretic peptide ,Confidence interval ,Treatment Outcome ,Endocrinology ,Original Article ,Female ,030211 gastroenterology & hepatology ,medicine.symptom ,Hyponatremia ,business ,Antidiuretic Hormone Receptor Antagonists ,medicine.drug - Abstract
Objective Hyponatremia is frequently observed in patients with decompensated liver cirrhosis and it is also related to a poor prognosis. The vasopressin V2-receptor antagonist tolvaptan is used to treat cirrhotic patients with ascites and increases the serum sodium (Na) level. In this study, we investigated (i) whether or not correction of the Na level improves the prognosis of cirrhotic patients with ascites and (ii) predictors of normalization of the serum Na level after tolvaptan therapy. Methods This was a single-center retrospective study. A total of 95 Japanese cirrhotic patients (60 men, median age 63 years) were enrolled and received tolvaptan orally after hospitalization for ascites treatment. The serum Na level was monitored during the period of tolvaptan treatment. The laboratory data and survival rates of patients who achieved serum Na levels of
- Published
- 2017
45. A case of gastrojejunocolic fistula with steatohepatitis
- Author
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Masakazu Yamamoto, Bunei Iizuka, Teppei Omori, Fukiko Kinoshita, Mikiko Taneichi, Makiko Taniai, Shinichi Nakamura, Yoji Nagashima, Ayumi Ito, Katsutoshi Tokushige, Etsuko Hashimoto, and Michio Itabashi
- Subjects
Adult ,Gastric Fistula ,Male ,Enteroscopy ,medicine.medical_specialty ,Balloon Enteroscopy ,Biopsy ,Fistula ,medicine.medical_treatment ,Anastomosis ,Gastroenterology ,Colonic Diseases ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Intestinal Fistula ,medicine ,Humans ,Ultrasonography ,Barium enema ,Billroth II ,Gastrojejunocolic fistula ,business.industry ,Transverse colon ,Jejunal Diseases ,General Medicine ,medicine.disease ,Surgery ,Fatty Liver ,Liver ,Duodenal Ulcer ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Steatohepatitis ,Gastroenterostomy ,Tomography, X-Ray Computed ,business - Abstract
A man in his 30s, who had undergone retrocolic Billroth II reconstruction for perforated duodenal ulcer, presented with watery diarrhea for 2 years and suspected fatty liver. He was referred to our hospital for management of chronic diarrhea, weight loss, hepatopathy and hypoalbuminemia. Initial upper and lower gastrointestinal endoscopies were negative. Since a small bowel lesion was suspected, peroral single-balloon enteroscopy was performed, which identified feces-like residue near the Billroth II anastomotic site and a connection to the colon separate from the afferent and efferent loops. Transanal single-balloon enteroscopy identified a fistula between the gastrojejunal anastomosis and transverse colon, with the scope reaching the stomach transanally. Barium enema confirmed flow of contrast medium from the transverse colon through the fistula to the anastomotic site, allowing the diagnosis of gastrojejunocolic fistula. Liver biopsy showed relatively severe steatohepatitis (Brunt's classification: stage 2-3, grade 3). Resection of the anastomotic site and partial transverse colectomy were performed to remove the fistula, followed by Roux-en-Y reconstruction. Postoperatively, watery diarrhea resolved and the stools became normal. Hepatopathy and hypoproteinemia improved. One year later, liver biopsy showed marked improvement of steatosis. This case demonstrated marked improvement of both diarrhea/nutritional status and steatohepatitis after treatment of gastrojejunocolic fistula, suggesting that the fistula caused non-alcoholic steatohepatitis.
- Published
- 2016
46. Response to tolvaptan and its effect on prognosis in cirrhotic patients with ascites
- Author
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Makiko Taniai, Tomomi Kogiso, Yuichi Ikarashi, Nobuyuki Torii, Mutsuki Kobayashi, Kazuhisa Kodama, Kuniko Yamamoto, Etsuko Hashimoto, and Katsutoshi Tokushige
- Subjects
medicine.medical_specialty ,Creatinine ,Hepatology ,business.industry ,Urinary system ,Tolvaptan ,Urine ,030204 cardiovascular system & hematology ,Gastroenterology ,Urine sodium ,Excretion ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Infectious Diseases ,Endocrinology ,chemistry ,Internal medicine ,Ascites ,medicine ,030211 gastroenterology & hepatology ,medicine.symptom ,business ,Blood urea nitrogen ,medicine.drug - Abstract
Aims The vasopressin V2 receptor antagonist tolvaptan has been used for the treatment of cirrhotic patients with ascites; however, no predictor of efficacy and prognosis has been developed. Here, we evaluated candidate predictors of response to tolvaptan treatment. Methods This was a single-center retrospective study. Overall, 97 Japanese cirrhotic patients (60 males, median age 63 years), who were hospitalized for ascites treatment including oral tolvaptan coupled with conventional diuretics, were enrolled. The efficacy of tolvaptan was defined as a urination increase of ≥ 500 mL or a urine volume ≥ 2,000 mL/day on the day following treatment. The prognosis of tolvaptan treatment was evaluated by the post-treatment survival time by Kaplan–Meier analysis. Results Tolvaptan therapy was effective in 67% of cirrhotic patients. Patients showed -1.5 (-17.2 to +6.2) kg change in body weight and 40% achieved ≥ 2.0 kg reduction in body weight after 1 week of treatment. Platelet counts, urine sodium (Na) level, and urine Na/potassium (Na/K) ratio were higher, and the blood urea nitrogen (BUN)/creatinine (Cr) ratio was lower, in cases showing a response to tolvaptan. The combination of a BUN/Cr ratio ≥ 17.5 and urine Na/K ratio
- Published
- 2016
47. The characteristics and risk factors of hepatocellular carcinoma in nonalcoholic fatty liver disease without cirrhosis
- Author
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Katsutoshi Tokushige, Nishino Takayoshi, Masakazu Yamamoto, Tomomi Kogiso, Katagiri Satoshi, Makiko Taniai, Maki Tobari, Kazuhisa Kodama, Araida Tatsuo, and Etsuko Hashimoto
- Subjects
Liver Cirrhosis ,Male ,medicine.medical_specialty ,Cirrhosis ,Carcinoma, Hepatocellular ,Alcohol Drinking ,Disease ,Gastroenterology ,Sex Factors ,Non-alcoholic Fatty Liver Disease ,Risk Factors ,Internal medicine ,Nonalcoholic fatty liver disease ,Medicine ,Humans ,Prospective Studies ,Risk factor ,neoplasms ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Hepatology ,business.industry ,Fatty liver ,Liver Neoplasms ,Middle Aged ,medicine.disease ,Fibrosis ,digestive system diseases ,Survival Rate ,Liver ,Hepatocellular carcinoma ,Female ,Liver function ,Steatosis ,business - Abstract
Background and aim We evaluated the characteristics of hepatocellular carcinoma (HCC) in patients who had non-alcoholic fatty liver disease (NAFLD) without cirrhosis. Methods We prospectively followed NAFLD patients at our University hospital. NAFLD was diagnosed from detection of steatosis by histology or imaging, no alcohol intake, and exclusion of other liver diseases. Cirrhosis was defined by histological features, imaging data, and symptoms. We compared NAFLD-related HCC with or without cirrhosis and non-cirrhotic NAFLD with or without HCC. Results There were 48 non-cirrhotic HCC patients and 71 cirrhotic HCC patients. Multiple logistic regression analysis revealed that other than liver function factors, male gender (OR: 5.603, 95%CI: 1.577-19.900), light drinker (OR: 2.797, 95%CI: 1.031-7.589), and tumor size (OR: 1.031, 95%CI 1.009-1.055) differ significantly between these two groups. The recurrence rate was significantly lower in the non-cirrhotic HCC group than the cirrhotic HCC group, with risk factors being des-γ-carboxy prothrombin and the number of HCCs. The non-cirrhotic HCC group showed significantly better survival because of absence of non-cancerous liver failure. Comparison between non-cirrhotic NAFLD patients with or without HCC (n = 612) revealed the following risk factors for HCC: male gender (OR: 7.774, 95%CI: 2.176-27.775), light drinker (OR: 4.893, 95%CI: 1.923-12.449), and high FIB4 index (OR 2.634, 95%CI: 1.787-3.884). Conclusion In patients with non-cirrhotic NAFLD, important risk factors for HCC were male gender, alcohol consumption, and the FIB4 index. HCC recurrence and survival were only influenced by the tumor stage. We should be aware of alcohol consumption as a modifiable risk factor for HCC.
- Published
- 2019
48. A case of Fontan-related hepatocellular carcinoma successfully treated with proton beam therapy
- Author
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Yuri Ogasawara, Katsutoshi Tokushige, Kazuhisa Kodama, Hideyuki Sakurai, Tomomi Kogiso, Haruko Numajiri, Makiko Taniai, and Takaomi Sagawa
- Subjects
Adult ,medicine.medical_specialty ,Liver tumor ,Carcinoma, Hepatocellular ,Radiofrequency ablation ,medicine.medical_treatment ,Transposition of Great Vessels ,Heterotaxy Syndrome ,Fontan Procedure ,Inferior vena cava ,law.invention ,Fontan procedure ,03 medical and health sciences ,0302 clinical medicine ,Postoperative Complications ,law ,medicine ,Proton Therapy ,Humans ,medicine.diagnostic_test ,business.industry ,Liver Diseases ,Liver Neoplasms ,Gastroenterology ,Magnetic resonance imaging ,General Medicine ,medicine.disease ,Magnetic Resonance Imaging ,medicine.vein ,Great arteries ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,030211 gastroenterology & hepatology ,Polysplenia ,Female ,Radiology ,business ,Tomography, X-Ray Computed - Abstract
A 27-year-old woman was admitted to our hospital due to a liver tumor. She had been born late at 41 weeks of gestation and had heterotaxy syndrome, polysplenia, and complete transposition of the great arteries. She underwent percutaneous balloon angioplasty at 5 years of age and the Fontan procedure at 6 years of age. At 25 years of age, computed tomography detected liver congestion. Her alpha-fetoprotein level increased from 13 to 2098 ng/dL (L3 fraction 1.8%) at 27 years of age. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid enhanced magnetic resonance imaging showed a 22-mm liver tumor in the second liver segment. The liver tumor was enhanced in the arterial phase and washed-out in the hepatobiliary phase; the patient was, therefore, diagnosed with hepatocellular carcinoma. Radiofrequency ablation and surgery were not indicated due to the proximity of the tumor to the inferior vena cava. Therefore, proton beam therapy was selected as conservative therapy, and a dose of 74 Gray equivalents in 37 fractions was administered at the University of Tsukuba Hospital. There were no severe adverse events and she survived for 38 months after treatment without recurrence.
- Published
- 2019
49. POGLUT1, the putative effector gene driven by rs2293370 in primary biliary cholangitis susceptibility locus chromosome 3q13.33
- Author
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Takeaki Sato, Hironori Sakai, Tatsuki Ichikawa, Atsushi Naganuma, Atsushi Tanaka, Tatsuo Kanda, Hirotoshi Ebinuma, Masataka Seike, Hidetaka Shibata, Tatsuji Komatsu, Mikio Zeniya, Shinji Uemoto, Toshiki Nikami, Yoko Nakamura, Osamu Yokosuka, Yoshiyuki Ueno, Masaru Harada, Masao Nagasaki, Keisuke Ario, Yuki Hitomi, Haruhiro Yamashita, Yutaka Mano, Michio Senju, Makiko Taniai, Kazuhiko Yamauchi, Satoshi Yamagiwa, Makoto Nakamuta, Fujio Makita, Kazuhiro Sugi, Kouki Matsushita, Kiyoshi Migita, Masahiro Ito, Noriaki Naeshiro, Hajime Takikawa, Kaname Kojima, Noboru Hirashima, Norihiro Kokudo, Shinji Katsushima, Shinya Nagaoka, Hironao Takahashi, Kuniaki Arai, Kazumoto Murata, Etsuko Hashimoto, Masanori Abe, Tsutomu Yamashita, Naohiko Masaki, Minoru Nakamura, Hiroshi Kouno, Atsumasa Komori, Kiyoshi Furuta, Shinji Shimoda, Kaname Yoshizawa, Yoshihiko Maehara, Iwao Yabuuchi, Seigo Abiru, Shotaro Sakisaka, Rie Sugimoto, Hideo Nishimura, Takashi Himoto, Yasuaki Takeyama, Yosuke Kawai, Hiromasa Ohira, Satoru Joshita, Yusuke Shimada, Katsushi Tokunaga, Masahiro Kikuchi, Minae Kawashima, Masao Honda, Hiroshi Kamitsukasa, Toshiki Komeda, Yoshihiro Aiba, Eiji Mita, Hajime Ohta, Nao Nishida, Kazuhiko Nakao, Hiroshi Yatsuhashi, Takeji Umemura, Masaharu Koda, Seiji Tsunematsu, Hirotaka Kouno, Teruko Arinaga-Hino, Kazuko Ueno, Masaaki Shimada, Hitomi Nakamura, Shuichi Kaneko, and Akinobu Takaki
- Subjects
0301 basic medicine ,Adult ,Male ,In silico ,lcsh:Medicine ,Genome-wide association study ,Locus (genetics) ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Article ,Pathogenesis ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Japan ,SNP ,Humans ,lcsh:Science ,Gene ,Aged ,Genetics ,Aged, 80 and over ,Multidisciplinary ,Effector ,Liver Cirrhosis, Biliary ,lcsh:R ,Middle Aged ,030104 developmental biology ,Glucosyltransferases ,lcsh:Q ,Female ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Article, Scientific reports.9 :102(2019)
- Published
- 2019
50. Impact of continued administration of tolvaptan on cirrhotic patients with ascites
- Author
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Makiko Taniai, Kazuhisa Kodama, Tomomi Kogiso, Takaomi Sagawa, and Katsutoshi Tokushige
- Subjects
Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Tolvaptan ,Renal function ,Gastroenterology ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,lcsh:RA1190-1270 ,Ammonia ,Internal medicine ,Ascites ,medicine ,Body weight reduction ,Humans ,Pharmacology (medical) ,Vasopressin V2-receptor antagonist ,Serum Albumin ,lcsh:Toxicology. Poisons ,Aged ,Pharmacology ,Prothrombin time ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,lcsh:RM1-950 ,Body Weight ,Albumin ,Retrospective cohort study ,Middle Aged ,Long-term outcome ,lcsh:Therapeutics. Pharmacology ,Treatment Outcome ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Female ,Liver function ,medicine.symptom ,business ,Complication ,Antidiuretic Hormone Receptor Antagonists ,medicine.drug ,Research Article - Abstract
Background The vasopressin V2-receptor antagonist tolvaptan is used to treat cirrhotic patients with ascites. We investigated the outcome of long-term treatment. Methods This was a single-center retrospective study. Overall, 170 cirrhotic patients (95 males, median age 63 years) were enrolled and received tolvaptan orally after hospitalization for ascites, which included treatment with conventional diuretics. We compared patients who withdrew tolvaptan treatment after
- Published
- 2018
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