57 results on '"Takuya Genda"'
Search Results
2. Post‐treatment serum Wisteria floribunda agglutinin‐positive mac‐2‐binding protein level is a useful predictor of hepatocellular carcinoma development after hepatitis C virus eradication
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Shunsuke Sato, Yuji Ikeda, Sho Sato, Hironori Tsuzura, Yuji Kita, Daishi Kabemura, Noboru Yatagai, Nozomi Amano, Yuji Shimada, Takuya Genda, and Ayato Murata
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hepatitis C virus ,medicine.medical_specialty ,Hepatitis C virus ,Wisteria floribunda agglutinin‐positive mac‐2‐binding protein ,RC799-869 ,medicine.disease_cause ,interferon‐based therapy ,Gastroenterology ,Interferon ,interferon‐free therapy ,Internal medicine ,Medicine ,Wisteria floribunda agglutinin ,direct‐acting antiviral drug ,Hepatology ,Receiver operating characteristic ,biology ,business.industry ,Hazard ratio ,Original Articles ,hepatocellular carcinoma ,Diseases of the digestive system. Gastroenterology ,Wisteria floribunda ,biology.organism_classification ,medicine.disease ,digestive system diseases ,Hepatocellular carcinoma ,Original Article ,sustained virological response ,business ,Mac 2 binding protein ,medicine.drug - Abstract
Aims Recent advances of direct‐acting antiviral drugs for hepatitis C virus (HCV) have dramatically improved the sustained virologic response (SVR) rate, but hepatocellular carcinoma (HCC) development rarely occurs even in patients who achieve an SVR. Wisteria floribunda agglutinin‐positive mac‐2‐binding protein (WFA+‐M2BP) was recently developed as a noninvasive biomarker of liver fibrosis. However, the association between the WFA+‐M2BP level and HCC development after the achievement of an SVR is unclear. Methods and Results We examined the association between WFA+‐M2BP and HCC development in 522 HCV patients who achieved an SVR (Interferon [IFN]‐based therapy, n = 228; IFN‐free therapy, n = 294). Multivariate analysis revealed that a high WFA+‐M2BP level at SVR week 24 after treatment (SVR24) (hazard ratio [HR] = 1.215, P = 0.020), low platelet counts (HR = 0.876, P = 0.037), and old age (HR = 1.073, P = 0.012) were independent risk factors for HCC development regardless of the treatment regimen. Receiver operator characteristics curve analysis revealed that a WFA+‐M2BP level at SVR24 of ≥1.62 cut‐off index (COI) was the cut‐off value for the prediction of HCC development (adjusted HR = 12.565, 95% CI 3.501–45.092, P, The assessment of liver fibrosis using the WFA+‐M2BP level at SVR24 is a useful predictor of HCC development after HCV eradication even in the IFN‐free therapy era.
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- 2021
3. Does restricting fluid volume impact post-ERCP pancreatitis in patient with heart disease?
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Kouhei Matsumoto, Yuji Shimada, Ko Tomishima, Sho Sato, Daishi Kabemura, Shigeto Ishii, Akihito Nagahara, Toshio Fujisawa, Ayato Murata, Nozomi Amano, Noboru Yatagai, Takuya Genda, Hiroyuki Isayama, Shunsuke Sato, and Hironori Tsuzura
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medicine.medical_specialty ,Heart disease ,Heart Diseases ,education ,RC799-869 ,Gastroenterology ,Endoscopic retrograde cholangiopancreatography ,Risk Factors ,Internal medicine ,medicine ,Humans ,Risk factor ,Cholangiopancreatography, Endoscopic Retrograde ,Common Bile Duct ,medicine.diagnostic_test ,Common bile duct ,business.industry ,Incidence (epidemiology) ,Incidence ,fluid volume ,Diseases of the digestive system. Gastroenterology ,medicine.disease ,Major duodenal papilla ,medicine.anatomical_structure ,Pancreatitis ,cardiovascular system ,Original Article ,business ,Body mass index - Abstract
Background: To investigate patient characteristics and the risk of post endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in association with fluid volume and type during ERCP. Methods: Two hundred and forty seven of 480 patients with naïve papilla undergoing therapeutic ERCP between April 2013 and March 2018 were enrolled for the study. The following patient characteristics were investigated: age, sex, body mass index, previous diseases (heart disease, renal failure, cerebrovascular disorders, coexisting malignancy and pulmonary disease), history of PEP, common bile duct diameter, diverticula and volume of fluid infused 24 hours after the procedure. All ERCP cases had naïve papilla and had undergone treatment. Results: The incidence of PEP was 8.5%. Significant differences were observed in the volume of fluid infused between patients without and with a history of heart disease (1,380 vs. 1,755 mL). The mean volume of the infused fluid was significantly lower in the PEP than non-PEP group (1,483 vs. 1,688 mL, P = 0.02). Moreover, PEP incidence differed according to a fluid infusion cutoff of 1,000 mL (7 vs. 11 cases of PEP in those with ≦1,000 mL and >1,000 mL fluid volume, respectively, P < 0.001). Conclusion: Restricted fluid volume was a newly identified risk factor for PEP, particularly in patients with heart and renal diseases as comorbidities.
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- 2021
4. Elevated serum tyrosine concentration is associated with a poor prognosis among patients with liver cirrhosis
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Yuji Ikeda, Noboru Yatagai, Ayato Murata, Yuji Shimada, Nozomi Amano, Daishi Kabemura, Sho Sato, Takuya Genda, Yuji Kita, Hironori Tsuzura, and Shunsuke Sato
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medicine.medical_specialty ,Cirrhosis ,Hepatology ,business.industry ,Proportional hazards model ,medicine.medical_treatment ,Hazard ratio ,Retrospective cohort study ,Liver transplantation ,medicine.disease ,Gastroenterology ,Confidence interval ,Infectious Diseases ,Hepatocellular carcinoma ,Internal medicine ,medicine ,Tyrosine ,business - Abstract
Aim Chronic liver insufficiency is often associated with changes in amino acid metabolism. We evaluated whether change in serum amino acid concentrations had prognostic value among patients with liver cirrhosis. Methods This retrospective study evaluated 158 patients who had been hospitalized with cirrhosis. Baseline serum concentrations of branched-chain amino acids (BCAAs) and tyrosine, as well as the BCAA-to-tyrosine ratio (BTR), were evaluated. Cox proportional hazards analysis was used to calculate the hazard ratios (HRs) for factors that were associated with mortality or liver transplantation. Results Among the 158 patients, baseline measurements revealed decreased serum BCAA concentrations for 59 patients (37.3%), elevated serum tyrosine concentrations for 80 patients (50.6%), and a decreased BTR for 114 patients (72.2%). During a median follow-up of 3.0 years, death or liver transplantation occurred at a rate of 0.136 cases/1 person-year. Multivariable analysis revealed that transplant-free survival was independently predicted by older age, male sex, comorbid hepatocellular carcinoma, Child-Turcotte-Pugh score, and serum tyrosine concentration. Receiver operating characteristic curve analysis revealed that a serum tyrosine concentration of >110 µmol/L was the optimal cut-off value for predicting transplant-free survival (adjusted HR: 1.89, 95% confidence interval: 1.15-3.11, P = 0.012). Kaplan-Meier analysis revealed a significant difference in the 5-year transplant-free survival probability between patients with high and low serum tyrosine concentrations (42.1% vs. 60.7%, P Conclusions Elevated serum tyrosine concentration, but not changes in serum BCAA concentration or the BTR, may indicate a high risk of death or liver transplantation for patients with liver cirrhosis. This article is protected by copyright. All rights reserved.
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- 2021
5. Hepatitis B Surface Antigen Decline during Sofosbuvir and Ribavirin Therapy in Hepatitis B Inactive Carriers Who Were Co-infected with Hepatitis C
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Ayato Murata, Yuji Kita, Sho Sato, Daishi Kabemura, Hironori Tsuzura, Noboru Yatagai, Takuya Genda, Shunsuke Sato, Yuji Shimada, Nozomi Amano, and Yuji Ikeda
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hepatitis C virus ,HBsAg ,Hepatitis B virus ,Sofosbuvir ,ribavirin ,Hepatitis C virus ,Case Report ,Hepacivirus ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Hepatitis b surface antigen ,sofosbuvir ,Antiviral Agents ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal Medicine ,medicine ,Humans ,Retrospective Studies ,Hepatitis B Surface Antigens ,business.industry ,Ribavirin ,virus diseases ,General Medicine ,Hepatitis C ,Hepatitis B ,Hepatitis C, Chronic ,medicine.disease ,Virology ,digestive system diseases ,hepatitis B surface antigen ,chemistry ,030211 gastroenterology & hepatology ,business ,medicine.drug - Abstract
Direct-acting antiviral (DAA) therapy carries a potential risk of inducing hepatitis B virus (HBV) reactivation. However, the HBV kinetics during and after DAA therapy in patients co-infected with hepatitis C virus (HCV) and HBV remain unknown. We retrospectively evaluated the HBV kinetics during and after sofosbuvir/ribavirin therapy in four HBV inactive carriers co-infected with HCV. HCV was eradicated in all patients. Changes in HBV-DNA levels during treatment differed among patients. The hepatitis B surface antigen (HBsAg) levels uniformly decreased (mean -0.530 logIU/mL) by the end of treatment and returned to near the baseline in all patients. Sofosbuvir/ribavirin therapy thus demonstrated a suppressive effect on HBsAg.
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- 2021
6. Analysis of the safety of pretransplant corticosteroid therapy in patients with acute liver failure and late‐onset hepatic failure in Japan
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Takuro Hisanaga, Isao Hidaka, Isao Sakaida, Nobuaki Nakayama, Akio Ido, Naoya Kato, Yasuhiro Takikawa, Kazuaki Inoue, Masahito Shimizu, Takuya Genda, Shuji Terai, Hirohito Tsubouchi, Hajime Takikawa, Satoshi Mochida, and null Intractable Hepato‐Biliary Disease
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medicine.medical_specialty ,corticosteroid ,medicine.drug_class ,medicine.medical_treatment ,Late onset ,RC799-869 ,Liver transplantation ,03 medical and health sciences ,late‐onset hepatic failure ,0302 clinical medicine ,Internal medicine ,medicine ,In patient ,Fulminant hepatitis ,Hepatology ,liver transplantation ,business.industry ,Gastroenterology ,Liver failure ,Original Articles ,acute liver failure ,Diseases of the digestive system. Gastroenterology ,Corticosteroid therapy ,030220 oncology & carcinogenesis ,Corticosteroid ,Original Article ,030211 gastroenterology & hepatology ,Bilirubin levels ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
Background and Aim In Japan, corticosteroids have been commonly used as a part of multidisciplinary therapy for patients with acute liver failure and late‐onset hepatic failure. However, there is controversy regarding the development of infections and other complications. In this study, the influence of corticosteroids on patient outcomes after liver transplantation was investigated. Methods This study included 167 patients with acute liver failure and late‐onset hepatic failure who underwent liver transplantation between 2010 and 2015. The effects of pretransplant corticosteroid therapy on patient outcomes were evaluated using a database constructed by the subcommittee for fulminant hepatitis in the Intractable Hepato‐Biliary Diseases Study Group of Japan. Results The subacute type and the median total bilirubin levels were higher in those receiving corticosteroids than in those not receiving corticosteroids. Although infections tended to be higher in patients receiving corticosteroids, pretransplant corticosteroid administration did not affect the survival rates. The duration from corticosteroid initiation to liver transplantation was longer in patients who developed infections. The survival rates, however, did not differ between patients with and without infections. Conclusions Corticosteroids were administered to patients with poor prognoses. Otherwise, the overall outcome in those administered corticosteroids was not significantly different from that in those administered without corticosteroids. Although infectious complications tended to occur, they were generally controllable and nonfatal. Pretransplant corticosteroid therapy may be permissible, with regarding for infections and performed within the minimum duration., Corticosteroids are commonly used for acute liver failure in Japan. However, there is controversy regarding the development of complications. We analyzed the influence of corticosteroids on patient outcomes after liver transplantation. Although, infections tended to occur in patients receiving corticosteroids, pretransplant corticosteroid didn't affect the survival rates. The duration from corticosteroid initiation to liver transplantation was longer in patients with infections. Pretransplant corticosteroid may be a permissible treatment with caution for infections and within the minimum duration.
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- 2021
7. Mucinous Cystadenocarcinoma of the Pancreas with Cyst Infection in a Male Patient
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Kouhei Matsumoto, Mako Ushio, Hironori Tsuzura, Hiroyuki Isayama, Nozomi Amano, Shunsuke Sato, Yuki Fukumura, Sho Sato, Toshio Fujisawa, Ko Tomishima, Yuji Shimada, Takuya Genda, and Ayato Murata
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Male ,Pathology ,medicine.medical_specialty ,CA-19-9 Antigen ,pancreatic cancer ,Case Report ,030204 cardiovascular system & hematology ,Cystadenocarcinoma, Mucinous ,03 medical and health sciences ,Pancreatectomy ,0302 clinical medicine ,Pancreatic cancer ,Internal Medicine ,medicine ,Humans ,Cyst ,Pancreas ,MCC ,Type 1 diabetes ,Intraductal papillary mucinous neoplasm ,business.industry ,cyst in cyst ,General Medicine ,MCN ,Middle Aged ,medicine.disease ,Cystic Neoplasm ,Pancreatic Neoplasms ,medicine.anatomical_structure ,Male patient ,030211 gastroenterology & hepatology ,Pancreatic Cyst ,Mucinous cystadenocarcinoma ,Tomography, X-Ray Computed ,business - Abstract
Follow-up computed tomography revealed a 40-mm pancreatic tail cyst in a 59-year-old man with type 1 diabetes mellitus. An intraductal papillary mucinous neoplasm was suspected; mucinous cystic neoplasm (MCN) was not considered because the patient was a man. During follow-up, cyst infection occurred but was improved by conservative treatment. At the 24-month follow up examination, cyst nodules had developed, corresponding to an increase in the carbohydrate antigen 19-9 level. Mucinous cystadenocarcinoma (MCC) was diagnosed pathologically based on distal pancreatectomy. A diagnosis of male MCN/MCC is often delayed, which may lead to a poor prognosis. MCN infection is also rare and poorly recognized. We observed an atypical male case of MCN/MCC.
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- 2020
8. Eosinophilic Gastroenteritis in an Ulcerative Colitis Patient During Treatment with Tumor Necrosis Factor-alpha Antagonist
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Sho Takahashi, Yuji Shimada, Hironori Tsuzura, Sho Sato, Akihito Nagahara, Takuya Genda, Shunsuke Sato, Nozomi Amano, Sho Hayashida, Ayato Murata, and Yuji Ikeda
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Male ,eosinophilic gastroenteritis ,Abdominal pain ,medicine.medical_specialty ,tumor necrosis factor-alpha antagonist ,Prednisolone ,Case Report ,030204 cardiovascular system & hematology ,Gastroenterology ,ascites ,03 medical and health sciences ,Esophagus ,0302 clinical medicine ,Ileum ,Internal medicine ,Eosinophilia ,Ascites ,Internal Medicine ,medicine ,Eosinophilic gastroenteritis ,Humans ,Endoscopy, Digestive System ,Glucocorticoids ,ulcerative colitis ,business.industry ,Stomach ,Rectum ,Antibodies, Monoclonal ,Colonoscopy ,General Medicine ,Middle Aged ,Eosinophil ,medicine.disease ,Ulcerative colitis ,Enteritis ,Golimumab ,Eosinophils ,medicine.anatomical_structure ,Gastritis ,Colitis, Ulcerative ,Tumor Necrosis Factor Inhibitors ,030211 gastroenterology & hepatology ,medicine.symptom ,Tomography, X-Ray Computed ,business ,medicine.drug - Abstract
A 45-year-old man with steroid-dependent ulcerative pancolitis was hospitalized with frequent diarrhea, abdominal pain and distension 3 months after induction of golimumab, a tumor necrosis factor-alpha antagonist. Computed tomography showed wall thickening from the stomach to the colon and massive ascites. Peripheral blood test revealed eosinophilia. A large number of eosinophils were observed in the ascites fluid. Although esophagogastroduodenoscopy showed no abnormal findings and colonoscopy showed ulcerative colitis with a Mayo endoscopic subscore of 1, eosinophil infiltration was histologically observed. Based on these findings, we diagnosed him with eosinophilic gastroenteritis and started prednisolone. Consequently, his eosinophil counts and abdominal symptoms dramatically improved.
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- 2020
9. Outcome of patients with acute liver failure awaiting liver transplantation in Japan
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Shotaro Sakisaka, Koji Umeshita, Satoshi Mochida, Yoshiyuki Ueno, Eiji Tanaka, Takafumi Ichida, Seiji Kawasaki, Ayano Inui, Hiroto Egawa, Yukihiro Inomata, Takuya Genda, and Hiroyuki Furukawa
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Coma ,medicine.medical_specialty ,Multivariate analysis ,Hepatology ,business.industry ,Proportional hazards model ,medicine.medical_treatment ,Hazard ratio ,Liver failure ,Liver transplantation ,03 medical and health sciences ,0302 clinical medicine ,Infectious Diseases ,030220 oncology & carcinogenesis ,Internal medicine ,Cohort ,Medicine ,030211 gastroenterology & hepatology ,medicine.symptom ,Risk factor ,business - Abstract
Aim To clarify the outcome and predictive factors in patients with acute liver failure (ALF) awaiting deceased donor liver transplantation (DDLT) in Japan. Methods Of the DDLT candidates in Japan between 2007 and 2016, 264 adult patients with ALF were retrospectively enrolled in this study. Factors associated with DDLT and waiting-list mortality were assessed using the Cox proportional hazard model. The DDLT and transplant-free survival probabilities were evaluated using Kaplan-Meier analysis and the log-rank test. Results The waiting-list registration year after the Transplant Law revision in 2010 was a significant factor associated with DDLT. The adjusted hazard ratio indicated that DDLT probability after 2010 was four times higher than that before, and the 28-day cumulative DDLT probability was more than 35%. The median survival time of the entire cohort was 40 days. Multivariate analysis identified the following three factors associated with waiting-list mortality: age, coma grade, and international normalized ratio. The transplant-free survival probabilities were significantly stratified by the number of risks, and patients with all three risks showed extremely poor short-term prognosis (median survival time = 23 days). Conclusions The DDLT probability of ALF patients increased after the law revision in 2010; however, patients at high risk of short-term waiting-list mortality might need emergent living donor transplantation.
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- 2020
10. The effectiveness and safety of glecaprevir/pibrentasvir in chronic hepatitis C patients with refractory factors in the real world: a comprehensive analysis of a prospective multicenter study
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Naoki Hotta, Toshihide Shima, Norio Itokawa, Akio Moriya, Katsuhiko Iwakiri, Takashi Kumada, Makoto Nakamuta, Chisa Kondo, Shin Maeda, Toru Ishikawa, Shigeru Mikami, Taeang Arai, Shinichi Fujioka, Atsushi Hiraoka, Shinya Fukunishi, Makoto Chuma, Yasuhito Tanaka, Hidenori Toyoda, Hironao Okubo, Haruki Uojima, Noritomo Shimada, Takeshi Okanoue, Takehiro Akahane, Takuya Genda, Joji Tani, Shintaro Ogawa, Koichi Takaguchi, Tsunamasa Watanabe, Masanori Atsukawa, Hiroshi Abe, Hiroki Ikeda, Chikara Ogawa, Akihito Tsubota, Asahiro Morishita, Toru Asano, Yoshihiko Tachi, Akito Nozaki, and Tadashi Ikegami
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Adult ,Male ,medicine.medical_specialty ,Pyrrolidines ,Adolescent ,Sustained Virologic Response ,Antiviral Agents ,Gastroenterology ,Drug Administration Schedule ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Refractory ,Quinoxalines ,Internal medicine ,Genotype ,medicine ,Humans ,Prospective Studies ,Adverse effect ,Aged ,Aged, 80 and over ,Sulfonamides ,Hepatology ,business.industry ,Glecaprevir ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Pibrentasvir ,Drug Combinations ,Regimen ,030220 oncology & carcinogenesis ,Benzimidazoles ,Female ,030211 gastroenterology & hepatology ,business ,Kidney disease - Abstract
Direct-acting anti-virals (DAAs) have markedly improved the effectiveness of anti-viral therapy for chronic hepatitis C (CHC) patients. In a phase III trial in Japan, treatment with the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir (G/P) resulted in a small number of patients with refractory factors. We aimed to evaluate the effectiveness and safety of G/P, especially among patients with these refractory factors, and the influence of these factors on treatment. In a prospective, multicenter study involving 33 medical institutions, 1439 patients were treated with G/P, and their efficacy, safety, and most frequent adverse effects (AEs) were analyzed. Overall SVR12 rates were 99.1% (1397/1410) in the per-protocol-analysis, and genotype sustained virologic response SVR12 rates were: genotype 1, 99.4% (707/711); genotype 2, 99.4% (670/674); genotype 3, 80.0% (16/20). DAA-naive patients (p = 0.008) with HCV genotype except 3 (genotype 1 vs. 3, p = 2.68 × 10–5; genotype 2 vs. 3, p = 3.28 × 10–5) had significantly higher SVR12 rates. No significant difference was observed between CKD stage 1–3 (99.1% [1209/1220]) and chronic kidney disease (CKD) stage 4–5 (98.9% [188/190]) patients, or between cirrhotic (99.0% [398/402]) and non-cirrhotic (99.1% [999/1008]) patients. Multiple logistic regression analysis revealed that genotype 3 [OR 33.404, 95% CI (7.512–148.550), p value (p = 4.06 × 10–5)] and past experience of IFN-free DAAs [OR 3.977, 95% CI (1.153–13.725), p value (p = 0.029)] were both significantly independent predictors of non-SVR12. AEs were reported in 28.2% of patients, and 1.6% discontinued treatment owing to drug-related AEs. AEs were significantly higher in CKD stage 4–5 (41.6% [79/190]) than CKD stage 1–3 (26.1% [319/1220]) patients (p = 2.00 × 10–5). AEs were also significantly higher in cirrhotic (38.6% [155/402]) than in non-cirrhotic (24.1% [243/1008]) (p = 2.91 × 10–18) patients. G/P regimen is highly effective and safe to treat CHC patients even with refractory factors such as CKD and advanced liver fibrosis. However, patients with past experience of IFN-free DAA treatment and genotype 3, CKD stage 4 or 5, and advanced liver fibrosis should be more closely observed.
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- 2020
11. Real‐world experience of 12‐week direct‐acting antiviral regimen of glecaprevir and pibrentasvir in patients with chronic hepatitis C virus infection
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Toshihide Shima, Shigeru Mikami, Etsuko Iio, Tadashi Ikegami, Yasuhito Tanaka, Shinichi Fujioka, Takashi Kumada, Akio Moriya, Akihito Tsubota, Hiroshi Abe, Toru Asano, Akito Nozaki, Hiroki Ikeda, Takehiro Akahane, Joji Tani, Kojiro Michitaka, Kunihiko Tsuji, Toru Ishikawa, Satoshi Yasuda, Naoki Yamashita, Takuya Genda, Akemi Tsutsui, Chikara Ogawa, Koichi Takaguchi, Tsunamasa Watanabe, Yoshihiko Tachi, Masanori Atsukawa, Shinya Fukunishi, Asahiro Morishita, Tomomi Okubo, Makoto Nakamuta, Makoto Chuma, Tsutomu Masaki, Haruki Uojima, Atsushi Hiraoka, Hironao Okubo, Hidenori Toyoda, Katsuhiko Iwakiri, and Noritomo Shimada
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Adult ,Male ,medicine.medical_specialty ,Pyrrolidines ,Time Factors ,Sustained Virologic Response ,Hepatitis C virus ,medicine.disease_cause ,Antiviral Agents ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Quinoxalines ,Internal medicine ,Humans ,Medicine ,Prospective Studies ,Prospective cohort study ,Adverse effect ,Aged ,Sulfonamides ,Hepatology ,business.industry ,Gastroenterology ,Glecaprevir ,Hepatitis C, Chronic ,Middle Aged ,Pibrentasvir ,Clinical trial ,Drug Combinations ,Regimen ,Treatment Outcome ,Tolerability ,030220 oncology & carcinogenesis ,Benzimidazoles ,Female ,030211 gastroenterology & hepatology ,business ,Follow-Up Studies - Abstract
BACKGROUND In clinical trials, a pangenotype direct-acting antiviral (DAA) regimen consisting of glecaprevir (GLE) and pibrentasvir (PIB) exhibited high virologic efficacy and tolerability in patients with hepatitis C virus (HCV) infection. This study sought to confirm these findings in real-world settings, focusing on patients with cirrhosis, history of DAA failure, or HCV genotype 3 who were treated with a 12-week regimen in a large multicenter study from Japan. METHODS In a nationwide multicenter prospective cohort study, we analyzed background characteristics, tolerability, and treatment outcome of patients who underwent a 12-week GLE/PIB regimen. RESULTS Of 1190 patients, 509 (42.8%) underwent the 12-week regimen, and the remaining patients underwent an 8-week regimen. The rate of sustained virologic response (SVR) of patients treated with the 12-week regimen was 99.0%, comparable with that of patients treated with the 8-week regimen. The adverse events were observed in 29.1% of patients. The main adverse event was pruritus, which was observed in 14.7%. Ten patients (2.0%) discontinued therapy during treatment period. CONCLUSION The 12-week GLE/PIB regimen was well-tolerated with high virologic efficacy in patients with cirrhosis, experience of DAA, or HCV genotype 3; tolerability and SVR rate were comparable with those of DAA-naive, non-cirrhotic, non-genotype 3 patients who underwent 8-week regimen.
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- 2019
12. Cholestatic Liver Injury Induced by Pembrolizumab in a Patient with Lung Adenocarcinoma
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Kazuhisa Takahashi, Yosuke Miyashita, Munechika Hara, Shinichi Sasaki, Takuya Genda, Shin-ichiro Iwakami, Masahiro Fujioka, Kana Kurokawa, and Naoko Iwakami
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Male ,hepatotoxicity ,medicine.medical_specialty ,Lung Neoplasms ,immune checkpoint inhibitor ,Case Report ,Adenocarcinoma of Lung ,Pembrolizumab ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,Antineoplastic Agents, Immunological ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Adverse effect ,Lung cancer ,Liver injury ,Cholestasis ,Lung ,business.industry ,Ursodeoxycholic Acid ,General Medicine ,Middle Aged ,medicine.disease ,Pathophysiology ,Ursodeoxycholic acid ,Treatment Outcome ,medicine.anatomical_structure ,Adenocarcinoma ,cholestatic liver injury ,business ,medicine.drug - Abstract
The anti-programmed cell death-1 protein monoclonal antibody, pembrolizumab is an immune checkpoint inhibitor. While it improves the prognoses of patients with advanced non-small-cell lung cancer, it has been reported to induce various kinds of immune-related adverse events, including hepatotoxicity. Despite the frequency of hepatotoxicity, there is only limited information available regarding the pathophysiology and treatment. We herein report a 48-year-old man with lung adenocarcinoma who was treated with pembrolizumab and developed cholestatic liver injury. In this case, the importance of evaluating the histology of hepatotoxicity and the effectiveness of ursodeoxycholic acid for cholestatic liver injury is indicated.
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- 2019
13. Nationwide survey for patients with acute-on-chronic liver failure occurring between 2017 and 2019 and diagnosed according to proposed Japanese criteria
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Mureo Kasahara, Masanori Abe, Isao Sakaida, Naoya Kato, Takuya Genda, Hajime Takikawa, Nobuaki Nakayama, Yoshihito Uchida, Tomoaki Tomiya, Hayato Uemura, Yukinori Imai, Masahito Shimizu, Hiromasa Ohira, Ayano Inui, Hitoshi Yoshiji, Kazuaki Chayama, Yasuhiro Takikawa, Ryuzo Abe, Shuji Terai, Satoshi Mochida, Kazuaki Inoue, Akio Ido, Kiyoshi Hasegawa, and Atsushi Tanaka
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Prothrombin time ,Liver Cirrhosis ,medicine.medical_specialty ,Cirrhosis ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Gastroenterology ,Alcoholic hepatitis ,Acute-On-Chronic Liver Failure ,Odds ratio ,Hepatology ,Liver transplantation ,medicine.disease ,Prognosis ,Japan ,Internal medicine ,medicine ,Etiology ,Odds Ratio ,Humans ,business ,Child ,Survival rate - Abstract
The significance of the 2018 Japanese diagnostic criteria for acute-on-chronic liver failure (ACLF) has not yet been evaluated. A nationwide survey was performed for patients with ACLF occurring between 2017 and 2019. Cirrhotic patients with a Child–Pugh score of 5–9 were diagnosed as having ACLF when liver failure (serum bilirubin level of ≥ 5.0 mg/dL and a prothrombin time international normalization rate [INR] of ≥ 1.5) occurred within 28 days after an acute insult. Patients who fulfilled either criterion (total serum bilirubin or INR) and/or those with indeterminate Child–Pugh scores at baseline were also enrolled. Among the 501 enrolled patients, 183 patients (37%) were diagnosed as having ACLF. The etiologies of the cirrhosis and acute insults were alcohol intake/abuse in 114 (62%) and 75 (41%) patients, respectively. Sixty-eight patients (37%) were also diagnosed as having severe alcoholic hepatitis. The survival rate without liver transplantation was 48% among the ACLF patients and 71% in the remaining patients (P
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- 2021
14. A case of primary biliary cholangitis overlapping with type 2 autoimmune hepatitis
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Takuya Genda, Shunsuke Sato, Ayato Murata, Kenichi Harada, Kohei Matsumoto, Yuji Shimada, Nozomi Amano, Hironori Tsuzura, Sho Sato, Ko Tomishima, and Katsuyori Iijima
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Adult ,Cholagogues and Choleretics ,medicine.medical_specialty ,Prednisolone ,Autoimmune hepatitis ,Gastroenterology ,Mitochondrial Proteins ,03 medical and health sciences ,0302 clinical medicine ,Cholestasis ,Internal medicine ,medicine ,Humans ,Aspartate Aminotransferases ,Glucocorticoids ,Autoantibodies ,Hepatitis ,medicine.diagnostic_test ,Liver Cirrhosis, Biliary ,business.industry ,Ursodeoxycholic Acid ,Alanine Transaminase ,Overlap syndrome ,General Medicine ,Hepatology ,medicine.disease ,Hepatitis, Autoimmune ,Immunoglobulin M ,Immunoglobulin G ,030220 oncology & carcinogenesis ,Liver biopsy ,Female ,030211 gastroenterology & hepatology ,business ,medicine.drug ,Anti-mitochondrial antibody - Abstract
A 42-year-old woman was admitted to our hospital with cholestatic liver injury. Serological examination revealed anti-mitochondrial M2 antibody positivity and anti-nuclear antibody and anti-smooth muscle antibody negativity. Histological examination of the first liver biopsy revealed chronic nonsuppurative destructive cholangitis with epithelioid granulomas. Ursodeoxycholic acid therapy successfully treated her cholestasis. Sixteen months later, she developed acute icteric hepatitis with elevation of serum aspartate and alanine aminotransferase levels. Anti-mitochondrial M2 positivity and anti-nuclear antibody and anti-smooth muscle antibody negativity persisted at that time. However, it became clear that anti-liver kidney microsomal type 1 antibody was positive. Histological examination of the second liver biopsy demonstrated scarce interface hepatitis and evident parenchymal inflammation and centrilobular zonal necrosis. Her liver biochemical test results promptly improved with the addition of prednisolone therapy. Considering the findings, she was diagnosed with primary biliary cholangitis-type 2 autoimmune hepatitis overlap syndrome. According to a literature review, this is an extremely rare autoimmune overlap syndrome.
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- 2019
15. The efficacy and safety of glecaprevir plus pibrentasvir in 141 patients with severe renal impairment: a prospective, multicenter study
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Chikara Ogawa, Katsuhiko Iwakiri, Hiroshi Abe, Takashi Kumada, Haruki Uojima, Shinya Fukunishi, Naoki Hotta, Tadashi Ikegami, Akito Nozaki, Takuya Genda, Kunihiko Tsuji, Makoto Nakamuta, Chisa Kondo, Noritomo Shimada, Yasuhito Tanaka, Hidenori Toyoda, Takehiro Akahane, Koichi Takaguchi, Tsunamasa Watanabe, Masanori Atsukawa, Yoshio Aizawa, Yoshihiko Tachi, Kojiro Michitaka, Toshihide Shima, and Akihito Tsubota
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Adult ,Cyclopropanes ,Male ,Drug ,medicine.medical_specialty ,Aminoisobutyric Acids ,Pyrrolidines ,Proline ,Sustained Virologic Response ,Lactams, Macrocyclic ,media_common.quotation_subject ,Antiviral Agents ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Leucine ,Renal Dialysis ,Quinoxalines ,Internal medicine ,Humans ,Medicine ,Pharmacology (medical) ,Prospective Studies ,030212 general & internal medicine ,Renal Insufficiency, Chronic ,Stage (cooking) ,Adverse effect ,Aged ,media_common ,Aged, 80 and over ,Sulfonamides ,Hepatology ,business.industry ,Incidence (epidemiology) ,Gastroenterology ,Glecaprevir ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Pibrentasvir ,Benzimidazoles ,Drug Therapy, Combination ,Female ,030211 gastroenterology & hepatology ,business ,Kidney disease - Abstract
BACKGROUND Patients with chronic hepatitis C are often complicated by chronic kidney disease (CKD). AIM To evaluate the efficacy, safety and pharmacokinetics of glecaprevir/pibrentasvir in patients with severe renal impairment. METHODS In a prospective, multicentre study involving 35 medical institutions, 832 genotype 1-3 patients were treated with glecaprevir/pibrentasvir. The efficacy and safety of glecaprevir/pibrentasvir were analysed for patients with CKD stage 4 or 5. Multivariate analysis was performed to identify the factors associated with the most frequently observed adverse event. In patients undergoing haemodialysis, a pharmacokinetic study was conducted to investigate the dialysability of the drugs: plasma samples were obtained from the arterial and venous sides of a dialyser to serially measure drug concentrations. RESULTS The subjects comprised 141 patients (32 with CKD stage 4 and 109 with CKD stage 5), of whom 100 were undergoing haemodialysis. All but one stage 5 CKD patients undergoing haemodialysis achieved sustained virologic response (99.3%). Adverse events were observed in 39.7% of subjects: pruritus was the most frequent (30.5%), and was significantly associated with haemodialysis. In the pharmacokinetic study, no arterial-venous differences in the plasma concentrations of glecaprevir/pibrentasvir were detected during the haemodialysis sessions. CONCLUSIONS Glecaprevir/pibrentasvir was highly effective and safe in chronic hepatitis C patients with severe renal impairment. Haemodialysis was associated with increased incidence of pruritus, which was the most frequent adverse event, but had little or no influence on the drug concentrations, which indicated that their dialysability is very low and that no dose modification is required in patients undergoing haemodialysis. (UMIN registration no. 000032073).
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- 2019
16. Successful Management of Hemosuccus Pancreaticus due to Pancreatic Adenocarcinoma by Chemoradiotherapy
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Takuya Genda, Hironori Tsuzura, Yuji Shimada, Kouhei Matsumoto, Ayato Murata, Shunsuke Sato, Sho Sato, Ryo Wada, Toshio Fujisawa, Ko Tomishima, Hiroyuki Isayama, and Nozomi Amano
- Subjects
Adult ,Male ,medicine.medical_specialty ,Anemia ,030204 cardiovascular system & hematology ,Adenocarcinoma ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Pancreatic cancer ,Hemosuccus pancreaticus ,Internal Medicine ,medicine ,Humans ,Aged ,Pancreatic duct ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,Pancreatic Ducts ,Interventional radiology ,General Medicine ,Chemoradiotherapy ,Middle Aged ,medicine.disease ,Pancreatic Neoplasms ,medicine.anatomical_structure ,Treatment Outcome ,Pancreatic juice ,030211 gastroenterology & hepatology ,Female ,business ,Gastrointestinal Hemorrhage - Abstract
Management of hemosuccus pancreaticus (HP) due to pancreatic adenocarcinoma is problematic. This is the first report of the successful management of HP caused by pancreatic adenocarcinoma by chemoradiotherapy, which is a treatment option for cases with a high surgical risk that are not suitable for interventional radiology. In the present case, bloody pancreatic juice was detected in the main pancreatic duct, and anemia worsened without repeated blood transfusions. The patient ultimately underwent chemoradiotherapy comprising radiation of 3 Gy in 15 fractions concomitant with systemic chemotherapy of S-1. After the treatments, the anemia improved, and the patient was discharged on day 45.
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- 2020
17. Elevated serum procalcitonin levels and their association with the prognosis of patients with liver cirrhosis
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Akihito Nagahara, Sho Takahashi, Katuyori Iijima, Yuji Shimada, Nozomi Amano, Sho Sato, Yuji Ikeda, Hironori Tsuzura, Shunsuke Sato, Sho Hayashida, Ayato Murata, and Takuya Genda
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Liver Cirrhosis ,Gastrointestinal bleeding ,medicine.medical_specialty ,Multivariate analysis ,Cirrhosis ,Gastroenterology ,Procalcitonin ,Elevated serum ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,parasitic diseases ,medicine ,Humans ,Hepatic encephalopathy ,Retrospective Studies ,Hepatology ,Proportional hazards model ,business.industry ,bacterial infections and mycoses ,medicine.disease ,Prognosis ,030220 oncology & carcinogenesis ,Hepatic Encephalopathy ,030211 gastroenterology & hepatology ,Liver cancer ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
OBJECTIVES Bacterial infection is a major complication in patients with liver cirrhosis. Procalcitonin is an early diagnostic marker of bacterial infection. This study aimed to investigate the association between the serum procalcitonin levels and the prognosis of patients with liver cirrhosis. METHODS We retrospectively analyzed the serum procalcitonin levels in 236 hospitalized patients with liver cirrhosis. The impact of the serum procalcitonin level on their prognoses was evaluated using multivariate Cox proportional hazards analyses and the Kaplan-Meier method. RESULTS The serum procalcitonin level was higher (≥0.05 ng/mL) in 151 (64%) patients, and it was significantly higher in the patients with Child-Turcotte-Pugh class C than in those with Child-Turcotte-Pugh classes A/B. Patients with refractory ascites, hepatic encephalopathy, gastrointestinal bleeding, and bacterial infections had elevated serum procalcitonin levels. The multivariate analyses showed a serum procalcitonin level ≥0.05 ng/mL was an independent prognostic factor for liver cirrhosis (hazard ratio = 1.64; 95% confidence interval = 1.07-2.53; P = 0.024). During a median follow-up interval of 2.1 years, the three-year cumulative survival rates for the patients with normal and elevated serum procalcitonin levels were 72.9 and 56.0%, respectively (P
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- 2019
18. Ledipasvir‐sofosbuvir for treating Japanese patients with chronic hepatitis C virus genotype 2 infection
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Takuya Genda, Diana M. Brainard, John G. McHutchison, Hiroshi Yatsuhashi, Nobuyuki Enomoto, Yasuhiro Asahina, Yoshiyuki Ueno, Yasushi Matsuzaki, Takuma Matsuda, Yoshito Itoh, Anu Osinusi, Norifumi Kawada, Fusao Ikeda, Benedetta Massetto, Yasuhiro Takikawa, Deyuan Jiang, and Hadas Dvory-Sobol
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Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Time Factors ,Cirrhosis ,Sustained Virologic Response ,Sofosbuvir ,Hepacivirus ,Antiviral Agents ,Gastroenterology ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Japan ,Internal medicine ,Genotype ,medicine ,Clinical endpoint ,Humans ,030212 general & internal medicine ,Adverse effect ,Aged ,Aged, 80 and over ,Fluorenes ,Hepatology ,business.industry ,Ribavirin ,virus diseases ,Hepatitis C, Chronic ,Middle Aged ,Viral Load ,medicine.disease ,digestive system diseases ,Regimen ,Treatment Outcome ,chemistry ,Cohort ,Benzimidazoles ,Female ,030211 gastroenterology & hepatology ,Uridine Monophosphate ,business ,medicine.drug - Abstract
Background & aims Japanese patients with chronic hepatitis C virus (HCV) genotype 2 infection have high rates of sustained virological response (SVR) following 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir in combination with ribavirin, which was the standard of care at the time this study was undertaken. We assessed the efficacy of 12 weeks of treatment with a ribavirin-free regimen of ledipasvir-sofosbuvir. Methods In an open-label, Phase 3 trial we enrolled Japanese patients with chronic HCV genotype 2 infection, with or without compensated cirrhosis. In Cohort 1, participants were randomized 1:1 to receive ledipasvir-sofosbuvir (n = 106) or sofosbuvir + ribavirin (n = 108) for 12 weeks. In Cohort 2, 25 ribavirin-intolerant or -ineligible patients received ledipasvir-sofosbuvir for 12 weeks. The primary endpoint was SVR 12 weeks after therapy (SVR12). In Cohort 1 non-inferiority was assessed with a prespecified margin of 10%. Results One-third (33%) of patients were treatment experienced, and 14% had cirrhosis. In Cohort 1, SVR12 rates were 96% (95% CI, 91% to 99%) with ledipasvir-sofosbuvir and 95% (95% CI, 90% to 98%) with sofosbuvir plus ribavirin, thus achieving non-inferiority. Among ribavirin-intolerant/ineligible patients in Cohort 2, SVR12 was 96% (95% CI, 80% to 100%) with ledipasvir-sofosbuvir. Overall, the most common adverse events were nasopharyngitis, anaemia, and headache; anaemia was only observed in patients receiving ribavirin. The percentage of patients who discontinued treatment because of an adverse event was low (1%). Conclusions Among Japanese patients with HCV genotype 2, 12 weeks of treatment with ledipasvir-sofosbuvir resulted in high rates of SVR12 that were non-inferior to sofosbuvir + ribavirin.
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- 2018
19. A multicenter pilot survey to clarify the clinical features of patients with acute-on-chronic liver failure in Japan
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Shuji Terai, Hajime Takikawa, Satoshi Mochida, Takuya Genda, Nobuaki Nakayama, Tomoaki Tomiya, Akio Ido, Hayato Uemura, Yoshihito Uchida, Osamu Yokosuka, Isao Sakaida, Kazuaki Inoue, Yasuhiro Takikawa, and Masahito Shimizu
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medicine.medical_specialty ,Gastrointestinal bleeding ,Cirrhosis ,Hepatology ,Exacerbation ,business.industry ,Alcohol abuse ,Hepatitis B ,medicine.disease ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Infectious Diseases ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Etiology ,030211 gastroenterology & hepatology ,Decompensation ,business - Abstract
Aim To establish diagnostic criteria for acute-on-chronic liver failure (ACLF) in Japan, a multicenter pilot survey was carried out to examine the usefulness of overseas criteria in patients with chronic liver diseases manifesting acute decompensation. Methods Patients fulfilling the Asian-Pacific Association for the Study of the Liver (APASL), European Association for the Study of the Liver (EASL), or Chinese Medical Association (CMA) criteria for decompensation were enrolled from eight institutions in Japan, and the clinical features were evaluated. Results Among 112 patients, 109 patients (97.3%) fulfilled the APASL criteria for decompensation; 7 patients were excluded because the decompensation had been provoked by gastrointestinal bleeding. Consequently, 102 patients (91.1%) were diagnosed as having ACLF according to the APASL definition. Among the patients who fulfilled the APASL criteria for decompensation, the etiologies of the underlying liver diseases were alcohol abuse in 59 cases (54.1%) and hepatitis B or hepatitis C virus infection in 24 (22.0%). The acute insults were alcohol abuse in 50 (45.9%), bacterial infection in 26 (23.9%), and exacerbation of underlying liver disease in 14 (12.8%). Fifty-four patients (49.5%) satisfied the CMA criteria, but the survival rates were similar between patients who did and those who did not meet the criteria. When 84 patients with underlying cirrhosis were classified according to the EASL-Chronic Liver Failure (Clif) Consortium criteria, the survival rates differed according to grade: 67.6% (23/34) for patients without ACLF, and 41.2% (14/34) and 18.8% (3/16) for those with grade 1/2 and grade 3 ACLF, respectively. Conclusion The APASL definition was suitable for screening Japanese patients with ACLF, including those whose conditions were triggered by gastrointestinal bleeding, and the EASL-Clif Consortium criteria were useful for predicting outcome.
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- 2018
20. Proposed diagnostic criteria for acute-on-chronic liver failure in Japan
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Shuji Terai, Satoshi Mochida, Takuya Genda, Yasuhiro Takikawa, Nobuaki Nakayama, Osamu Yokosuka, Akio Ido, Masahito Shimizu, Isao Sakaida, Kazuaki Inoue, and Hajime Takikawa
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Prothrombin time ,Gastrointestinal bleeding ,medicine.medical_specialty ,Cirrhosis ,Hepatology ,medicine.diagnostic_test ,Exacerbation ,business.industry ,Alcohol abuse ,Disease ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Infectious Diseases ,030220 oncology & carcinogenesis ,Internal medicine ,Cohort ,medicine ,030211 gastroenterology & hepatology ,Liver function ,business - Abstract
To establish diagnostic criteria for acute-on-chronic liver failure (ACLF) in Japan, the Intractable Hepato-Biliary Disease Study Group of Japan undertook a multicenter pilot survey for patients fulfilling the Asian Pacific Association for the Study of the Liver (APASL), Association for the Study of the Liver-Chronic Liver Failure (EASL-Clif) Consortium, or Chinese Medical Association (CMA) diagnostic criteria for ACLF. The APASL criteria were suitable for screening Japanese patients with ACLF when patients whose conditions were triggered by gastrointestinal bleeding were included within the disease entity, and the EASL-Clif Consortium criteria were useful for classifying the severity of the patients' conditions. Based on these observations, the Study Group proposed the following diagnostic criteria for ACLF in Japan: patients with cirrhosis and a Child-Pugh score of 5-9 should be diagnosed as having ACLF when a deterioration of liver function (serum bilirubin level ≥5.0 mg/dL and prothrombin time value ≤40% of the standardized values and/or international normalization rate ≥1.5) caused by severe liver damage develops within 28 days after acute insults, such as alcohol abuse, bacterial infection, gastrointestinal bleeding, or the exacerbation of underlying liver diseases. The severities of the patients can be classified into four grades depending on the extent of the deterioration in organ functions, including kidney, cerebral, blood coagulation, circulatory and respiratory functions, as well as liver function. The usefulness of these novel criteria should be validated prospectively in a large-scale cohort in the future.
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- 2018
21. Efficacy and safety of rifaximin in Japanese patients with hepatic encephalopathy: A phase II/III, multicenter, randomized, evaluator-blinded, active-controlled trial and a phase III, multicenter, open trial
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Hitoshi Takagi, Atsushi Naganuma, Kazuyuki Suzuki, Yasuhiro Takikawa, Isao Sakaida, Hisataka Moriwaki, Takuya Genda, Katsuhiko Miyazawa, Yutaka Aoyagi, Shuhei Nishiguchi, Fuminori Moriyasu, Koichi Takaguchi, Takafumi Ichida, Shuji Terai, Toru Ishikawa, Yoshiyuki Sakai, Kiwamu Okita, and Ryujin Endo
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medicine.medical_specialty ,Lactitol ,Hepatology ,business.industry ,Hyperammonemia ,medicine.disease ,Gastroenterology ,Treatment period ,Portal systemic encephalopathy ,Rifaximin ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Infectious Diseases ,chemistry ,Randomized controlled trial ,law ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,030211 gastroenterology & hepatology ,Open label ,business ,Hepatic encephalopathy - Abstract
Aim The efficacy and safety of rifaximin in the treatment of hepatic encephalopathy (HE) are widely known, but they have not been confirmed in Japanese patients with HE. Thus, two prospective, randomized studies (a phase II/III study and a phase III study) were carried out. Methods Subjects with grade I or II HE and hyperammonemia were enrolled. The phase II/III study, which was a randomized, evaluator-blinded, active-comparator, parallel-group study, was undertaken at 37 institutions in Japan. Treatment periods were 14 days. Eligible patients were randomized to the rifaximin group (1200 mg/day) or the lactitol group (18-36 g/day). The phase III study was carried out in the same patients previously enrolled in the phase II/III study, and they were all treated with rifaximin (1200 mg/day) for 10 weeks. Results In the phase II/III study, 172 patients were enrolled. Blood ammonia (B-NH3 ) concentration was significantly improved in the rifaximin group, but the difference between the two groups was not significant. The portal systemic encephalopathy index (PSE index), including HE grade, was significantly improved in both groups. In the phase III study, 87.3% of enrolled patients completed the treatment. The improved B-NH3 concentration and PSE index were well maintained from the phase II/III study during the treatment period of the phase III study. Adverse drug reactions (ADRs) were seen in 13.4% of patients who received rifaximin, but there were no severe ADRs leading to death. Conclusion The efficacy of rifaximin is sufficient and treatment is well tolerated in Japanese patients with HE and hyperammonemia.
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- 2018
22. Nationwide survey for acute liver failure and late-onset hepatic failure in Japan
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Hirohito Tsubouchi, Osamu Yokosuka, Akio Ido, Tomoaki Tomiya, Isao Sakaida, Kazuaki Inoue, Shuji Terai, Masahito Shimizu, Satoshi Mochida, Hajime Takikawa, Masamitsu Nakao, Yasuhiro Takikawa, Takuya Genda, Nobuaki Nakayama, and Yoshihito Uchida
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Adult ,Male ,medicine.medical_specialty ,Hepatitis, Viral, Human ,medicine.medical_treatment ,Autoimmune hepatitis ,Liver transplantation ,medicine.disease_cause ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Risk Factors ,Internal medicine ,medicine ,Humans ,Survival rate ,Aged ,Hepatitis B virus ,Hepatitis ,business.industry ,Age Factors ,Liver Failure, Acute ,Middle Aged ,Hepatology ,Hepatitis B ,Prognosis ,medicine.disease ,Health Surveys ,Liver Transplantation ,Hepatitis, Autoimmune ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,Plasmapheresis ,Chemical and Drug Induced Liver Injury ,business ,Liver Failure - Abstract
A nationwide survey was performed to clarify the recent status of acute liver failure (ALF) and late-onset hepatic failure (LOHF) in Japan. Two-step surveys for patients with ALF and LOHF meeting the Japanese diagnostic criteria were performed annually in 782 hospitals. The clinical features of the patients were then compared to those reported in previous surveys. In total, 1554 and 49 patients with ALF and LOHF, respectively, who were seen between 2010 and 2015 were enrolled. The subjects were classified into 1280 patients with hepatitis (642 non-comatose and 638 comatose) and 323 patients without hepatitis (190 non-comatose and 133 comatose). Compared with patients seen between 1998 and 2009, an older patient age and a higher percentage of underlying extrahepatic disease were observed. Although hepatitis virus infection was the most frequent etiology, the percentage of patients with this etiology had decreased, compared with previous cohorts, while the percentages of patients with drug-induced liver injuries, autoimmune hepatitis, and an indeterminate etiology had increased. Liver transplantation was performed in 170 patients (10.6%), whereas artificial liver support with plasmapheresis and/or hemodiafiltration were performed for most of the comatose patients. The outcomes of comatose patients were unfavorable, similar to previous surveys, especially the outcomes of hepatitis B virus carriers, including those with de novo hepatitis B (survival rate of 5.4% without liver transplantation). Although the clinical features, including the etiologies, of patients with ALF and LOHF have changed, the outcomes of patients have not improved in recent years.
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- 2017
23. Survival in patients with Child-Pugh class C cirrhosis: Analysis of the liver transplant registry in Japan
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Shotaro Sakisaka, Hiroto Egawa, Yukihiro Inomata, Yoshiyuki Ueno, Eiji Tanaka, Satoshi Mochida, Ayano Inui, Takuya Genda, Takafumi Ichida, Koji Umeshita, Hiroyuki Furukawa, and Seiji Kawasaki
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Hepatitis B virus ,medicine.medical_specialty ,Cirrhosis ,Hepatology ,business.industry ,Proportional hazards model ,viruses ,medicine.medical_treatment ,Hazard ratio ,Liver transplantation ,medicine.disease ,medicine.disease_cause ,Gastroenterology ,digestive system diseases ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Infectious Diseases ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,030211 gastroenterology & hepatology ,Child-Pugh Class C ,business ,Survival analysis - Abstract
Aim Aim: To clarify the survival and prognostic factors in patients with Child–Turcotte–Pugh class C (CTP-C) cirrhosis. Methods From all candidates for deceased donor liver transplantation in Japan between 2007 and 2015, 1014 adult patients with CTP-C cirrhosis were retrospectively enrolled in this study. The hazard ratio (HR) of factors associated with mortality was estimated by the Cox proportional hazard model. The survival probabilities were evaluated by Kaplan–Meier analysis and the log–rank test. Results Median survival time of the entire cohort was 475 days. Univariate analysis identified age, CTP, Model for End-Stage Liver Disease (MELD) score, and primary biliary cholangitis (PBC) as significant variables associated with mortality and hepatitis B virus (HBV) infection as a close-to-significant variable. Multivariate analysis revealed that age-adjusted mortality risk increased by 59% and 12% per 1 score step up in CTP and MELD scores, respectively. The HRs for HBV infection and PBC were significant after adjustment for age and CTP score, and they showed a 26% lower risk and an 83% higher risk than hepatitis C virus (HCV) infection, respectively. After adjustment for age and MELD score, the HR was also significant for HBV infection, but lost statistical significance for PBC. The survival curves were well stratified by both CTP or MELD score and revealed significant difference in both HBV infection and PBC as compared to HCV infection. Conclusions In patients with CTP-C cirrhosis, CTP and MELD scores could well stratify the patients’ survival, and HBV infection and PBC as etiologies have an impact on survival.
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- 2017
24. Budd-Chiari Syndrome Associated With Hypereosinophilic Syndrome Treated by Deceased-Donor Liver Transplantation: A Case Report
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Nozomi Amano, Hideya Kamei, Takuya Genda, Masato Shizuku, Kanta Jobara, Atsushi Yoshizawa, Nobuhiko Kurata, and Yasuhiro Ogura
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Hypereosinophilia ,Liver transplantation ,Budd-Chiari Syndrome ,Gastroenterology ,Internal medicine ,Hypereosinophilic Syndrome ,Medicine ,Humans ,Transplantation ,medicine.diagnostic_test ,business.industry ,Hypereosinophilic syndrome ,Eosinophil ,Middle Aged ,medicine.disease ,Liver Transplantation ,medicine.anatomical_structure ,Treatment Outcome ,Angiography ,Budd–Chiari syndrome ,Prednisolone ,Surgery ,medicine.symptom ,business ,Transjugular intrahepatic portosystemic shunt ,medicine.drug - Abstract
Introduction: Budd-Chiari syndrome (BCS) associated with hypereosinophilic syndrome (HES) is very rare, and only a few reports have described its treatment. Furthermore, no report to date has described the performance of liver transplantation for the treatment of BCS associated with HES. We herein describe a 54-year-old man who underwent deceased-donor liver transplantation (DDLT) for treatment of BCS associated with HES. Case: A 54-year-old man was found to have an increased eosinophil count during a medical check-up. After exclusion of hematopoietic neoplastic diseases and secondary eosinophilia, idiopathic hypereosinophilia was diagnosed. Oral prednisolone was administered to the patient, and his eosinophil count immediately decreased to a normal level. He had an uneventful course without complications for 11 months but then presented with bloating and malaise. Imaging studies including ultrasonography, enhanced computed tomography, and angiography revealed BCS associated with HES. Transjugular intrahepatic portosystemic shunt failed because of complete obstruction of the hepatic veins. Therefore, the patient was introduced to our hospital for liver transplantation. DDLT was performed with venovenous bypass 1 month after the patient was placed on the DDLT waiting list. The explanted hepatic veins were completely occluded and organized. The patient’s eosinophil count was maintained at a normal level with prednisolone treatment after DDLT. Conclusions: Liver transplantation can be a treatment option for BCS associated with HES if neoplastic diseases and secondary eosinophilia have been excluded. Life-long oral steroid therapy is required to control HES even after liver transplantation., ファイル公開:2020-11-01
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- 2019
25. Prognostic significance of serum tyrosine concentration in patients with primary biliary cholangitis under ursodeoxycholic acid therapy
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Sho Takahashi, Ryo Wada, Sho Sato, Yuji Shimada, Takuya Genda, Katsuyori Iijima, Hironori Tsuzura, Nozomi Amano, Ayato Murata, Yuji Ikeda, Shunsuke Sato, Akihito Nagahara, and Sho Hayashida
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chemistry.chemical_classification ,medicine.medical_specialty ,Hepatology ,Receiver operating characteristic ,business.industry ,Hazard ratio ,Curve analysis ,Gastroenterology ,Confidence interval ,Ursodeoxycholic acid ,Amino acid ,Infectious Diseases ,chemistry ,Internal medicine ,medicine ,In patient ,Tyrosine ,business ,medicine.drug - Abstract
AIM Chronic liver insufficiency is often associated with alteration in amino acid metabolism. We evaluated the prognostic value of changes in serum amino acid concentrations in patients with primary biliary cholangitis. METHODS A total of 75 primary biliary cholangitis patients who started urusodeoxycholic acid therapy were retrospectively enrolled. Baseline serum concentrations of branched-chain amino acids and tyrosine, and branched-chain amino acid-to-tyrosine ratio were determined. The hazard ratios of factors associated with liver-related events were analyzed by Cox proportional hazard analysis. RESULTS Of the 75 patients enrolled, 12 showed a decrease in serum branched-chain amino acid levels, and 15 showed an increase in serum tyrosine levels. The branched-chain amino acid-to-tyrosine ratio decreased in 16 patients. During a median 5.6-year follow up, liver-related events occurred in 11 patients. Multivariate analysis showed that high serum tyrosine levels at baseline and high alkaline phosphatase levels 48 weeks after starting urusodeoxycholic acid therapy were independent risk factors for event occurrence. From the receiver operator characteristics curve analysis, serum tyrosine concentration >110 μmol/L was identified as a cut-off value with an adjusted hazard ratio of 20.9 (95% confidence interval 4.3-101.5, P
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- 2019
26. Clinical practice guidelines for hepatocellular carcinoma: The Japan Society of Hepatology 2017 (4th JSH-HCC guidelines) 2019 update
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Ryosuke Tateishi, Etsuro Hatano, Hiroaki Nagano, Yutaka Matsuyama, Hiroko Iijima, Shuichi Kaneko, Takeyuki Watadani, Takuji Torimura, Masatoshi Kudo, Hideyuki Sakurai, Mitsuo Shimada, Satoshi Kobayashi, Norihiro Kokudo, Nobuyuki Takemura, Hiroshi Igaki, Takuya Genda, Namiki Izumi, Tadatoshi Takayama, Shoji Kubo, Kiyoshi Hasegawa, and Takamichi Murakami
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medicine.medical_specialty ,Evaluation system ,Hepatology ,business.industry ,medicine.disease ,Clinical Practice ,03 medical and health sciences ,0302 clinical medicine ,Infectious Diseases ,030220 oncology & carcinogenesis ,Internal medicine ,Hepatocellular carcinoma ,medicine ,030211 gastroenterology & hepatology ,Medical physics ,business ,Grading (tumors) - Abstract
The fourth version of Clinical Practice Guidelines for Hepatocellular Carcinoma was revised by the Japan Society of Hepatology, according to the methodology of evidence-based medicine and partly to the Grading of Recommendations Assessment, Development, and Evaluation system, which was published in October 2017 in Japanese. New or revised recommendations were described, herein, with a special reference to the surveillance, diagnostic, and treatment algorithms.
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- 2019
27. Impact of aldo-keto reductase family 1 member B10 on the risk of hepatitis C virus-related hepatocellular carcinoma
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Takuya Genda, Sachiko Ishikawa, Tetsu Kikuchi, Ayato Murata, Akihito Nagahara, Sumio Watanabe, Katsuyori Iijima, Yutaka Narita, Hironori Tsuzura, Ryo Wada, Shunsuke Sato, Masashi Mori, Yoshio Kanemitsu, Takafumi Ichida, and Katsuharu Hirano
- Subjects
medicine.medical_specialty ,Pathology ,Hepatology ,business.industry ,Hepatitis C virus ,Hazard ratio ,Gastroenterology ,Aldo-Keto Reductase Family 1 member B10 ,Reductase ,medicine.disease ,medicine.disease_cause ,Lower risk ,digestive system diseases ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Internal medicine ,Medicine ,030211 gastroenterology & hepatology ,Cumulative incidence ,Risk factor ,business - Abstract
BACKGROUND AND AIM Aldo-keto reductase family 1 member B10 (AKR1B10), a cancer-related oxidoreductase, was recently reported to be upregulated in some chronic liver diseases. However, its relevance in hepatocellular carcinoma (HCC) development is not fully assessed, especially in patients with chronic hepatitis C virus (HCV) infection. METHODS Aldo-keto reductase family 1 member B10 expression in the liver of 550 patients with chronic HCV infection was immunohistochemically assessed and quantified. A multivariate Cox model was used to estimate the hazard ratios (HRs) of AKR1B10 expression for HCC development, and the cumulative incidence of HCC was evaluated using the Kaplan-Meier method. RESULTS Aldo-keto reductase family 1 member B10 expression in the patients ranged from 0% to 80%. During the median follow-up of 3.2 years, 43 of 550 patients developed HCC. Multivariate analysis demonstrated that high AKR1B10 expression (≥6%) was an independent risk factor for HCC (HR, 6.43; 95% confidence interval, 2.90-14.25; P
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- 2016
28. Aldo-keto reductase family 1 member B10 is associated with hepatitis B virus-related hepatocellular carcinoma risk
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Ryo Wada, Yutaka Narita, Masashi Mori, Sachiko Ishikawa, Tetsu Kikuchi, Katsuyori Iijima, Sumio Watanabe, Yuji Shimada, Yoshio Kanemitsu, Ken Sugimoto, Hironori Tsuzura, Shunsuke Sato, Ayato Murata, Takuya Genda, Masato Kamei, Katsuharu Hirano, Akihito Nagahara, and Takafumi Ichida
- Subjects
Hepatitis B virus ,medicine.medical_specialty ,Pathology ,Hepatology ,business.industry ,Proportional hazards model ,Hazard ratio ,Reductase ,Hepatitis B ,medicine.disease_cause ,medicine.disease ,Gastroenterology ,digestive system diseases ,03 medical and health sciences ,0302 clinical medicine ,Infectious Diseases ,030220 oncology & carcinogenesis ,Internal medicine ,Hepatocellular carcinoma ,medicine ,Carcinoma ,030211 gastroenterology & hepatology ,Risk factor ,business - Abstract
Aim Recent reports have indicated that aldo-keto reductase family 1 member B10 (AKR1B10), a cancer-related oxidoreductase, was upregulated in some chronic liver diseases. However, few studies have reported AKR1B10 expression in chronic hepatitis B virus (HBV)-infected patients. The aim of the present study was to analyze AKR1B10 expression and its relevance on hepatocellular carcinoma (HCC) development in patients with chronic HBV infection. Methods Expression of AKR1B10 in the liver of 119 chronic HBV-infected patients was assessed and quantified immunohistochemically. A multivariate Cox model was used to estimate the hazard ratios of AKR1B10 expression for HCC development. The cumulative incidences of HCC were evaluated using Kaplan–Meier analysis. Results Expression of AKR1B10 in the study cohort ranged from 0% to 84%. During the median follow-up time (6.2 years), 13 patients developed HCC. Multivariate analysis revealed that high AKR1B10 expression (≥15%) was an independent risk factor for HCC (hazard ratio, 10.8; 95% confidence interval, 3.0–38.6; P
- Published
- 2016
29. On-treatment Serum Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) Level and Risk of Hepatocellular Carcinoma Development in Patients with Chronic Hepatitis B during Nucleot(s)ide Analogue Therapy
- Author
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Sho Sato, Ko Tomishima, Shunsuke Sato, Ayato Murata, Hironori Tsuzura, Yuji Shimada, Katsuyori Iijima, Takuya Genda, Nozomi Amano, and Kohei Matsumoto
- Subjects
Male ,Gastroenterology ,lcsh:Chemistry ,chemistry.chemical_compound ,0302 clinical medicine ,Risk Factors ,Fibrosis ,Protein Isoforms ,Cumulative incidence ,lcsh:QH301-705.5 ,Spectroscopy ,Aged, 80 and over ,Membrane Glycoproteins ,Liver Neoplasms ,Hazard ratio ,hepatocellular carcinoma ,General Medicine ,Middle Aged ,Viral Load ,Prognosis ,Computer Science Applications ,Treatment Outcome ,risk factor ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Female ,030211 gastroenterology & hepatology ,Disease Susceptibility ,nucleot(s)ide analog ,Mac-2-binding protein glycosylation isomer ,Adult ,Hepatitis B virus ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Glycosylation ,Antiviral Agents ,Risk Assessment ,Article ,Catalysis ,Inorganic Chemistry ,Young Adult ,03 medical and health sciences ,Hepatitis B, Chronic ,Antigens, Neoplasm ,Internal medicine ,medicine ,Humans ,chronic hepatitis B ,In patient ,Physical and Theoretical Chemistry ,Risk factor ,Molecular Biology ,Aged ,business.industry ,Organic Chemistry ,Reproducibility of Results ,medicine.disease ,Confidence interval ,lcsh:Biology (General) ,lcsh:QD1-999 ,ROC Curve ,chemistry ,business ,Biomarkers - Abstract
We aimed to analyze the serum level of a novel fibrosis marker, Mac-2-binding protein glycosylation isomer (M2BPGi), and its predictive value for hepatocellular carcinoma (HCC) development in chronic hepatitis B (CHB) under nucleot(s)ide analogue (NA) therapy. Serum M2BPGi levels were quantified in 147 CHB patients at baseline, 48 weeks after starting NA therapy, and at the patients&rsquo, last visit. The serum M2BPGi level serially decreased at each time point. During the median follow-up time of 6.6 years, 14 of 147 patients developed HCC. Multivariate Cox proportional hazard analysis demonstrated that high serum M2BPGi at 48 weeks was an independent risk factor for HCC development. A cutoff value of M2BPGi at 48 weeks >, 1.5 showed an adjusted hazard ratio = 34.9 (95% confidence interval, 4.3&ndash, 284.9). The 3- and 5-year cumulative incidence of HCC in patients with low M2BPGi were 0.9% and 4.2%, respectively, whereas those in patients with high M2BPGi were 10.1% and 25.6%, respectively (p <, 0.001). In conclusion, Serum M2BPGi level at 48 weeks is a useful predictor for HCC development in patients with CHB who receive NA therapy.
- Published
- 2020
30. A case of ischemic gastroduodenal disease in a patient who was receiving hemodialysis treatment that was managed by conservative treatment
- Author
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Yuji Shimada, Akihito Nagahara, Sho Sato, Hironori Tsuzura, Shunsuke Sato, Ko Tomishima, Nozomi Amano, Yoshio Kanemitsu, Katsuyori Iijima, Ayato Murata, Takuya Genda, and Ryo Wada
- Subjects
Male ,medicine.medical_specialty ,Gastrointestinal bleeding ,Duodenum ,medicine.medical_treatment ,Blood Pressure ,Conservative Treatment ,Endoscopy, Gastrointestinal ,03 medical and health sciences ,0302 clinical medicine ,Ischemia ,Renal Dialysis ,Internal medicine ,Medicine ,Humans ,Diabetic Nephropathies ,Myocardial infarction ,Dialysis ,Aged ,Arteriosclerosis obliterans ,business.industry ,Cerebral infarction ,Ischemic Change ,Stomach ,Gastroenterology ,General Medicine ,medicine.disease ,Blood pressure ,030220 oncology & carcinogenesis ,Cardiology ,Kidney Failure, Chronic ,030211 gastroenterology & hepatology ,Hemodialysis ,business ,Gastrointestinal Hemorrhage - Abstract
A 69-year-old man was under maintenance dialysis due to diabetic renal failure. He had a drop in blood pressure during dialysis, developed hematemesis, and was transported to our hospital. Emergency upper gastrointestinal endoscopy revealed diffuse erosion, mucosal sloughing, and edematous mucosa in the upper body of the stomach to the posterior wall of the antrum and to the greater curvature, which were considered to be an ischemic change. His underlying diseases included diabetic renal failure, chronic arteriosclerosis obliterans, cerebral infarction, internal carotid artery stenosis, hypertension, and myocardial infarction. Blood evaluation showed only mild inflammation and no fibrinolytic hyperactivity. Contrast-enhanced computed tomography (CECT) showed no occlusion of blood vessels. It was considered that the patient had a transient ischemic change due to blood pressure drop. The patient's condition improved with conservative treatment.
- Published
- 2018
31. A case of primary hepatic neuroendocrine carcinoma concomitant with biliary dilatation inside a lesion
- Author
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Sachiko Ishikawa, Katuyori Iijima, Koichi Sato, Ryo Wada, Yoshio Kanemitsu, Ayato Murata, Akihito Nagahara, Shunsuke Sato, Yutaka Narita, Takuya Genda, Hironori Tsuzura, Tetsu Kikuchi, and Hiroshi Maekawa
- Subjects
Oncology ,medicine.medical_specialty ,Pathology ,Hepatology ,business.industry ,Bile duct ,medicine.medical_treatment ,Primary hepatic neuroendocrine carcinoma ,Lesion ,medicine.anatomical_structure ,Internal medicine ,Concomitant ,medicine ,medicine.symptom ,Hepatectomy ,business ,Biliary dilatation - Published
- 2015
32. Revised criteria for classification of the etiologies of acute liver failure and late-onset hepatic failure in Japan: A report by the Intractable Hepato-biliary Diseases Study Group of Japan in 2015
- Author
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Osamu Yokosuka, Hisataka Moriwaki, Hajime Takikawa, Yasuhiro Takikawa, Satoshi Mochida, Akio Ido, Takuya Genda, Nobuaki Nakayama, and Isao Sakaida
- Subjects
Drug ,medicine.medical_specialty ,Exacerbation ,media_common.quotation_subject ,Late onset ,medicine.disease_cause ,Asymptomatic ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Fulminant hepatitis ,media_common ,Hepatitis B virus ,Hepatology ,business.industry ,Liver failure ,virus diseases ,digestive system diseases ,Infectious Diseases ,030220 oncology & carcinogenesis ,Etiology ,030211 gastroenterology & hepatology ,medicine.symptom ,business - Abstract
In 2011, the Intractable Liver Diseases Study Group of Japan, established novel diagnostic criteria for "acute liver failure ", and published the classification criteria for the etiologies of acute liver failure and late-onset hepatic failure (LOHF) in 2013. According to this classification, HBV carriers showing acute hepatitis exacerbation were divided into 3 subgroups; asymptomatic or inactive HBV carriers without drug exposure, asymptomatic or inactive HBV carriers developing HBV reactivation during and after immunosuppressive therapies and/or antineoplastic chemotherapies and those with previously resolved HBV infection showing iatrogenic HBV reactivation. In an annual nationwide survey in 2013, however, a patient with previously resolved HBV infection was enrolled, in whom LOHF developed as a result of HBV reactivation despite in the absence of immunosuppressive therapies and/or antineoplastic chemotherapies. Thus, the study group revised the classification criteria in 2015; HBV carriers developing acute hepatitis exacerbation were classified into asymptomatic or inactive HBV carriers and patients with previously resolved HBV infection, and both groups were further sub-classified into those receiving immunosuppressive therapies and/or antineoplastic chemotherapies and those without such drugs exposure.
- Published
- 2016
33. Sofosbuvir plus ribavirin in Japanese patients with chronic genotype 2 <scp>HCV</scp> infection: an open‐label, phase 3 trial
- Author
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Mikio Yanase, Diana M. Brainard, Takeji Umemura, Steven J. Knox, Hadas Dvory-Sobol, Tetsuo Takehara, Yoshiyuki Ueno, Masa Omote, Kimberly L. Garrison, Takuya Genda, Bing Gao, Naoya Sakamoto, Masao Omata, Masashi Mizokami, Hitoshi Mochizuki, Kazushige Nirei, William T. Symonds, Hidenori Toyoda, Osamu Yokosuka, Namiki Izumi, Akinobu Ishizaki, Tatsuya Ide, Keisuke Hino, John G. McHutchison, Shuhei Nishiguchi, Yoichi Nishigaki, Hiroshi Yatsuhashi, Nobuo Toda, Fusao Ikeda, and Kunio Nakane
- Subjects
Adult ,Male ,medicine.medical_specialty ,Cirrhosis ,Drug-Related Side Effects and Adverse Reactions ,Genotype ,Sofosbuvir ,Hepatitis C virus ,Hepacivirus ,Pharmacology ,medicine.disease_cause ,Antiviral Agents ,Gastroenterology ,Young Adult ,chemistry.chemical_compound ,Liver disease ,Japan ,Virology ,Internal medicine ,Ribavirin ,medicine ,Clinical endpoint ,Humans ,Adverse effect ,Aged ,Hepatology ,business.industry ,virus diseases ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,digestive system diseases ,Treatment Outcome ,Infectious Diseases ,chemistry ,RNA, Viral ,Female ,Uridine Monophosphate ,business ,medicine.drug - Abstract
Genotype 2 hepatitis C virus (HCV) accounts for up to 30% of chronic HCV infections in Japan. The standard of care for patients with genotype 2 HCV - peginterferon and ribavirin for 24 weeks - is poorly tolerated, especially among older patients and those with advanced liver disease. We conducted a phase 3, open-label study to assess the efficacy and safety of an all-oral combination of the NS5B polymerase inhibitor sofosbuvir and ribavirin in patients with chronic genotype 2 HCV infection in Japan. We enrolled 90 treatment-naïve and 63 previously treated patients at 20 sites in Japan. All patients received sofosbuvir 400 mg plus ribavirin (weight-based dosing) for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after therapy (SVR12). Of the 153 patients enrolled and treated, 60% had HCV genotype 2a, 11% had cirrhosis, and 22% were over the aged 65 or older. Overall, 148 patients (97%) achieved SVR12. Of the 90 treatment-naïve patients, 88 (98%) achieved SVR12, and of the 63 previously treated patients, 60 (95%) achieved SVR12. The rate of SVR12 was 94% in patients with cirrhosis and in those aged 65 and older. No patients discontinued study treatment due to adverse events. The most common adverse events were nasopharyngitis, anaemia and headache. Twelve weeks of sofosbuvir and ribavirin resulted in high rates of SVR12 in treatment-naïve and previously treated patients with chronic genotype 2 HCV infection. The treatment was safe and well tolerated by patients, including the elderly and those with cirrhosis.
- Published
- 2014
34. Expression of Aldo-Keto Reductase Family 1 Member B10 in the Early Stages of Human Hepatocarcinogenesis
- Author
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Yoshio Kanemitsu, Takafumi Ichida, Hi ronori Tsuzura, Shunsuke Sato, Tetsu Kikuchi, Yutaka Narita, Masashi Mori, Katsuyori Iijima, Ryo Wada, Ayato Murata, Takuya Genda, Sachiko Ishikawa, and Katsuharu Hirano
- Subjects
Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Aldo-Keto Reductases ,Biology ,AKR1B10 ,HSP70 ,glypican-3 ,hepatocellular carcinoma ,chronic hepatitis ,cirrhosis ,Catalysis ,Article ,Inorganic Chemistry ,lcsh:Chemistry ,Chronic hepatitis ,Glypicans ,Aldehyde Reductase ,Internal medicine ,medicine ,Humans ,HSP70 Heat-Shock Proteins ,Physical and Theoretical Chemistry ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,Aged ,Hepatitis, Chronic ,Aged, 80 and over ,Aldo-keto reductase ,Organic Chemistry ,Liver Neoplasms ,Aldo-Keto Reductase Family 1 member B10 ,General Medicine ,Hepatology ,Middle Aged ,Immunohistochemistry ,digestive system diseases ,Computer Science Applications ,Up-Regulation ,Endocrinology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Female - Abstract
Aldo-keto reductase family 1, member B10 (AKR1B10), a cancer-related oxidoreductase, is expressed in well-differentiated hepatocellular carcinomas (HCCs). However, AKR1B10 levels are minimal in normal liver tissues (NLs), similar to the 70-kilodalton heat shock protein (HSP70) and glypican-3. Moreover, the role of AKR1B10 in chronic hepatitis or cirrhosis, which are considered preneoplastic conditions for HCC, has not been fully elucidated. The aim of this study was to evaluate the expression of AKR1B10, HSP70, and glypican-3 in 61 HCC tissue samples compared to corresponding non-tumorous liver tissues (NTs), comprising 42 chronic hepatitis and 19 cirrhosis cases to clarify the significance of molecular changes at the preneoplastic stages of HCC. Immunohistochemical analysis demonstrated that the median expression levels of AKR1B10 were higher in HCCs than in NTs (p < 0.001) and higher in NTs than NLs (p < 0.001) with 54.8%, 2.1%, and 0.3% expression in HCCs, NTs, and NLs, respectively. HSP70 and glypican-3 were expressed in HCCs, but minimally in NTs and NLs with no significant difference between expression in NTs and NLs. Furthermore, a multivariate analysis identified an association between hepatic steatosis and AKR1B10 expression in NTs (p = 0.020). Of the three protein expressed in well-differentiated HCCs, only AKR1B10 was upregulated in preneoplastic conditions, and a steatosis-related factor might influence its expression.
- Published
- 2014
35. Increase of fucosylated alpha-fetoprotein fraction at the onset of autoimmune hepatitis and acute liver failure
- Author
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Yasunobu Matsuda, Masaaki Takamura, Satoshi Yamagiwa, Toru Takahashi, Takuya Genda, Takafumi Ichida, Takeshi Suda, Yutaka Aoyagi, Toru Ishikawa, Tomoteru Kamimura, Yasushi Tamura, and Minoru Nomoto
- Subjects
medicine.medical_specialty ,Hepatology ,medicine.diagnostic_test ,business.industry ,digestive, oral, and skin physiology ,Liver failure ,Autoimmune hepatitis ,medicine.disease ,digestive system diseases ,Highly sensitive ,Infectious Diseases ,Endocrinology ,Internal medicine ,Immunoassay ,embryonic structures ,medicine ,In patient ,Clinical significance ,Alpha-fetoprotein ,business ,neoplasms ,Acute hepatitis - Abstract
Aim Increased serum α-fetoprotein (AFP) has been associated with a good prognosis following acute liver failure (ALF), but the levels of the fucosylated fraction of AFP (Lens culinaris agglutinin-reactive fraction of AFP [AFP-L3]) following acute liver injury remain unknown. The aim of the present study was to investigate the clinical significance of AFP and AFP-L3 in patients with acute liver injury. Methods We investigated the serum levels of AFP and highly sensitive AFP-L3% in 27 patients with acute-onset autoimmune hepatitis (AIH), 28 patients with acute hepatitis (AH) and 22 patients with ALF at the onset using a highly sensitive immunoassay (micro-total analysis system). Results The serum AFP levels were increased in patients with AIH, AH and ALF, but the levels did not significantly differ among them. However, the mean AFP-L3% level was significantly higher in patients with AIH than in patients with AH (P = 0.0039). Moreover, significantly more patients with AIH demonstrated AFP-L3 positivity (≥10%) when compared with patients with AH (P = 0.014). Although the percentage of AFP-L3 positivity increased with AFP levels, at low serum AFP levels (
- Published
- 2014
36. Su1103 – Does Ppi Play a Protective Role in Gastric Mucosa in Patients Taking Doacs? and Also in Patients Taking Vka?
- Author
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Akihito Nagahara, Yuji Shimada, Ayato Murata, Hironori Tsuzura, Sho Sato, Yuji Ikeda, Kohei Matsumoto, Takuya Genda, Katsuyori Iijima, Shunsuke Sato, Nozomi Amano, and Ko Tomishima
- Subjects
medicine.medical_specialty ,medicine.anatomical_structure ,Hepatology ,business.industry ,Internal medicine ,Gastroenterology ,Gastric mucosa ,Medicine ,In patient ,business - Published
- 2019
37. SAT-181-Efficacy and safety of glecaprevir/pibrentasvir in patients with severe renal impairment in Japan: A prospective, multicenter study (KTK 49 Liver Study Group)
- Author
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Hiroshi Abe, Norio Itokawa, Tadashi Ikegami, Toru Asano, Naoki Hotta, Yoshio Aizawa, Makoto Nakamuta, Chisa Kondo, Yasuhito Tanaka, Takuya Genda, Takashi Kumada, Shinya Fukunishi, Koichi Takaguchi, Tsunamasa Watanabe, Akihito Tsubota, Taeang Arai, Masanori Atsukawa, Etsuko Iio, Kojiro Michitaka, Katsuhiko Iwakiri, Haruki Uojima, Hidenori Toyoda, Hironao Okubo, Noritomo Shimada, Akira Asai, Akito Nozaki, Keizo Kato, Hiroki Ikeda, Shigeru Mikami, Shinichi Fujioka, Atsushi Hiraoka, and Chikara Ogawa
- Subjects
medicine.medical_specialty ,Hepatology ,Multicenter study ,business.industry ,Internal medicine ,medicine ,In patient ,Glecaprevir / pibrentasvir ,business - Published
- 2019
38. SAT-111-Procalcitonin level is a prognostic marker in patients with liver cirrhosis
- Author
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Shunsuke Sato, Hironori Tsuzura, Takuya Genda, and Sho Sato
- Subjects
medicine.medical_specialty ,Cirrhosis ,Hepatology ,business.industry ,Internal medicine ,medicine ,In patient ,medicine.disease ,business ,Gastroenterology ,Procalcitonin - Published
- 2019
39. Prediction of liver stiffness hepatocellular carcinoma in chronic hepatitis C patients on interferon-based anti-viral therapy
- Author
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Tetsu Kikuchi, Sachiko Ishikawa, Yutaka Narita, Katsuyori Iijima, Takuya Genda, Shunsuke Sato, Hironori Tsuzura, Ryo Wada, Takafumi Ichida, Katsuharu Hirano, and Yoshio Kanemitsu
- Subjects
medicine.medical_specialty ,Multivariate analysis ,Hepatology ,business.industry ,Incidence (epidemiology) ,Hazard ratio ,Gastroenterology ,medicine.disease ,digestive system diseases ,Surgery ,Interferon ,Internal medicine ,Hepatocellular carcinoma ,Cohort ,medicine ,Cumulative incidence ,Risk factor ,business ,medicine.drug - Abstract
Background and Aim The purpose of this study was to evaluate the usefulness of liver stiffness measurement (LSM) for assessing the risk of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients receiving interferon (IFN) therapy. Methods One hundred fifty-one CHC patients who underwent LSM and received IFN therapy were included in the estimation cohort, and 56 were included in the validation study. The cumulative HCC incidences were evaluated using Kaplan–Meier plot analysis and the log-rank test. Multivariate Cox proportional hazard analyses were used to estimate the hazard ratios (HRs) of variables for HCC. Results In the estimation cohort, 9 of 151 patients developed HCC during the median follow-up time of 722 days. Multivariate analysis identified three independent risk factors for HCC: LSM (≥ 14.0 kPa, HR 5.58, P = 0.020), platelet count (
- Published
- 2013
40. Clinical significance of cell cycle inhibitors in hepatocellular carcinoma
- Author
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Mami Osawa, Masaaki Takamura, Ayumi Sanpei, Toshifumi Wakai, Takafumi Ichida, Satoshi Yamagiwa, Yasunobu Matsuda, Takuya Genda, Masayuki Kubota, Yutaka Aoyagi, and Shun Fujimaki
- Subjects
Oncology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Carcinogenesis ,Protein degradation ,Biology ,Pathology and Forensic Medicine ,Cyclin D1 ,Cyclin-dependent kinase ,Internal medicine ,Biomarkers, Tumor ,medicine ,Animals ,Humans ,Molecular Biology ,Cyclin-Dependent Kinase Inhibitor p16 ,Kinase ,Cell Cycle ,Liver Neoplasms ,General Medicine ,Cell cycle ,HCCS ,Prognosis ,medicine.disease ,Hepatocellular carcinoma ,DNA methylation ,Cancer research ,biology.protein ,Cyclin-Dependent Kinase Inhibitor p27 - Abstract
It is well accepted that cell cycle regulators are strongly implicated in the progression of cancer development. p16 and p27 are potent cyclin-dependent kinase (CDK) inhibitors involved in G1 phase progression, and are regarded as adverse prognostic biomarkers for various types of cancers. It has been reported that the main mechanism for p16 inactivation is aberrant DNA methylation, while p27 is exclusively inactivated by proteasome-mediated protein degradation. We have found that p27 is decreased in around half of hepatocellular carcinomas (HCCs), and in some cases p27 is inactivated by inappropriate interaction with cyclin D1/CDK4 complexes. In such cases, p16 is concomitantly inactivated through DNA methylation. Taking into consideration the complex interaction between p16 and p27, a comprehensive analysis including p16 and p27 would be useful for predicting the prognosis of HCC patients.
- Published
- 2013
41. Waiting list mortality of patients with primary biliary cirrhosis in the Japanese transplant allocation system
- Author
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Hiroto Egawa, Yukihiro Inomata, Ayano Inui, Michio Sata, Takuya Genda, Shotaro Sakisaka, K Umeshita, Seiji Kawasaki, Hiroyuki Furukawa, Takafumi Ichida, and Eiji Tanaka
- Subjects
Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Tissue and Organ Procurement ,Multivariate analysis ,Adolescent ,Waiting Lists ,medicine.medical_treatment ,Liver transplantation ,Severity of Illness Index ,Gastroenterology ,End Stage Liver Disease ,Young Adult ,Liver disease ,Model for End-Stage Liver Disease ,Primary biliary cirrhosis ,Japan ,Internal medicine ,medicine ,Humans ,Aged ,Proportional Hazards Models ,Retrospective Studies ,Liver Cirrhosis, Biliary ,business.industry ,Proportional hazards model ,Patient Selection ,Age Factors ,Hepatitis C, Chronic ,Middle Aged ,Hepatology ,medicine.disease ,digestive system diseases ,Liver Transplantation ,Survival Rate ,Etiology ,Female ,business - Abstract
The present study aimed to evaluate etiology-based differences in the risk of waiting list mortality, and to compare the current Japanese transplant allocation system with the Child–Turcotte–Pugh (CTP) and the Model for End-Stage Liver Disease (MELD) scoring systems with regard to the risk of waiting list mortality in patients with primary biliary cirrhosis (PBC). Using data derived from all adult candidates for deceased donor liver transplantation in Japan from 1997 to 2011, we assessed factors associated with waiting list mortality by the Cox proportional hazards model. The waiting list mortality risk of PBC patients was further estimated with adjustment for each scoring system. Of the 1056 patients meeting the inclusion criteria, 743 were not on the list at the end of study period; waiting list mortality was 58.1 % in this group. In multivariate analysis, increasing age and PBC were significantly associated with an increased risk of waiting list mortality. In comparison with patients with hepatitis C virus (HCV) infection, PBC patients were at 79 % increased risk and had a shorter median survival time by approximately 8 months. The relative hazard of PBC patients was statistically significant with adjustment for CTP score and medical point score, which was the priority for ranking candidates in the Japanese allocation system. However, it lost significance with adjustment for MELD score. Stratification by MELD score indicated a comparable waiting list survival time between patients with PBC and HCV. PBC patients are at high risk of waiting list mortality in the current allocation system. MELD-based allocation could reduce this risk.
- Published
- 2013
42. Association of Visceral Obesity with High Viral Load and Histological Findings in Elderly Patients with Genotype 1 Chronic Hepatitis C
- Author
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Katsuyori Iijima, Shunsuke Sato, Katsuharu Hirano, Takafumi Ichida, Yoshio Kanemitsu, Yutaka Narita, Tetsu Kikuchi, Ryo Wada, Hironori Tsuzura, and Takuya Genda
- Subjects
Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Genotype ,Adipokine ,Comorbidity ,Hepacivirus ,Severity of Illness Index ,Gastroenterology ,Insulin resistance ,Adipokines ,Internal medicine ,Prevalence ,Internal Medicine ,medicine ,Humans ,Prospective Studies ,Aged ,Retrospective Studies ,Aged, 80 and over ,Adiponectin ,business.industry ,Leptin ,Age Factors ,General Medicine ,Hepatitis C, Chronic ,Middle Aged ,Viral Load ,medicine.disease ,Obesity, Abdominal ,Multivariate Analysis ,Female ,Steatosis ,Metabolic syndrome ,Tomography, X-Ray Computed ,business ,Viral load ,Dyslipidemia - Abstract
OBJECTIVE Genotype 1 chronic hepatitis C (G1CHC) is generally accompanied by metabolic disturbances related to visceral obesity, such as insulin resistance, steatosis, or dyslipidemia. Because these abnormalities negatively influence the clinical course of G1CHC, we sought to clarify the effect of visceral obesity on the pathophysiology of G1CHC. METHODS We evaluated 180G1CHC patients for the presence of visceral obesity on the basis of computed tomography findings. Multivariate analysis was performed to estimate the relationship between visceral obesity and demographic, viral, and biochemical characteristics of patients. The associations of visceral obesity with histological findings and serum adipokine levels were also analyzed. RESULTS Multiple logistic regression analysis revealed that visceral obesity was independently associated with metabolic syndrome, platelet count, high-density lipoprotein level, and serum viral load in elderly patients (≥65 years). Multiple linear regression analysis confirmed the association between visceral obesity and high viral load. However, visceral obesity was not correlated with viral load in non-elderly patients (
- Published
- 2013
43. Genome-Wide Association Study Identifies TLL1 Variant Associated With Development of Hepatocellular Carcinoma After Eradication of Hepatitis C Virus Infection
- Author
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Yoichi Hiasa, Nobuyuki Enomoto, Yasuhiro Asahina, Atsumasa Komori, Atsunori Kusakabe, Shintaro Ogawa, Koichi Takaguchi, Masanori Isogawa, Hitoshi Yoshiji, Kazuho Ikeo, Tatsuya Ide, Mina Nakagawa, Atsushi Suetsugu, Yosuke Kawai, Eiichi Tomita, Ken Shirabe, Takuya Genda, Shuhei Nishiguchi, Kaname Kojima, Eiji Kajiwara, Noritomo Shimada, Misako Matsubara, Akihiro Tamori, Namiki Izumi, Masayuki Kurosaki, Naoya Sakamoto, Hisayoshi Watanabe, Masao Honda, Isao Sakaida, Etsuko Iio, Yasuhito Tanaka, Masao Nagasaki, Tadashi Namisaki, Takashi Kumada, Yasuteru Kondo, Katsushi Tokunaga, Hiromi Sawai, Hidenori Toyoda, Junichi Sugihara, Kentaro Matsuura, Shuichi Kaneko, Mitsuo Shimada, Yoshito Itoh, Norifumi Kawada, Sohji Nishina, and Eiji Tanaka
- Subjects
0301 basic medicine ,Oncology ,Liver Cirrhosis ,Male ,Candidate gene ,Sustained Virologic Response ,Genome-wide association study ,medicine.disease_cause ,Choline ,Mice ,0302 clinical medicine ,Risk Factors ,Carbon Tetrachloride ,Liver Neoplasms ,Gastroenterology ,Age Factors ,Middle Aged ,Hepatocellular carcinoma ,030211 gastroenterology & hepatology ,Female ,alpha-Fetoproteins ,Liver cancer ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Tolloid-Like Metalloproteinases ,Hepatitis C virus ,Single-nucleotide polymorphism ,Biology ,Antiviral Agents ,Polymorphism, Single Nucleotide ,Diabetes Complications ,03 medical and health sciences ,Sex Factors ,Internal medicine ,medicine ,Hepatic Stellate Cells ,Animals ,Humans ,RNA, Messenger ,Serum Albumin ,Aged ,Hepatology ,Hepatitis C, Chronic ,medicine.disease ,digestive system diseases ,Introns ,Rats ,Fatty Liver ,030104 developmental biology ,Case-Control Studies ,Immunology ,Steatohepatitis ,Hepatic fibrosis ,Genome-Wide Association Study - Abstract
Background & Aims There is still a risk for hepatocellular carcinoma (HCC) development after eradication of hepatitis C virus (HCV) infection with antiviral agents. We investigated genetic factors associated with the development of HCC in patients with a sustained virologic response (SVR) to treatment for chronic HCV infection. Methods We obtained genomic DNA from 457 patients in Japan with a SVR to interferon-based treatment for chronic HCV infection from 2007 through 2015. We conducted a genome-wide association study (GWAS), followed by a replication analysis of 79 candidate single nucleotide polymorphisms (SNPs) in an independent set of 486 patients in Japan. The study end point was HCC diagnosis or confirmation of lack of HCC (at follow-up examinations until December 2014 in the GWAS cohort, and until January 2016 in the replication cohort). We collected clinical and laboratory data from all patients. We analyzed expression levels of candidate gene variants in human hepatic stellate cells, rats with steatohepatitis caused by a choline-deficient L-amino acid-defined diet, and a mouse model of liver injury caused by administration of carbon tetrachloride. We also analyzed expression levels in liver tissues of patients with chronic HCV infection with different stages of fibrosis or tumors vs patients without HCV infection (controls). Results We found a strong association between the SNP rs17047200, located within the intron of the tolloid like 1 gene ( TLL1 ) on chromosome 4, and development of HCC; there was a genome-wide level of significance when the results of the GWAS and replication study were combined (odds ratio, 2.37; P = 2.66 × 10 −8 ). Multivariate analysis showed rs17047200 AT/TT to be an independent risk factor for HCC (hazard ratio, 1.78; P = .008), along with male sex, older age, lower level of albumin, advanced stage of hepatic fibrosis, presence of diabetes, and higher post-treatment level of α-fetoprotein. Combining the rs17047200 genotype with other factors, we developed prediction models for HCC development in patients with mild or advanced hepatic fibrosis. Levels of TLL1 messenger RNA (mRNA) in human hepatic stellate cells increased with activation. Levels of Tll1 mRNA increased in liver tissues of rodents with hepatic fibrogenesis compared with controls. Levels of TLL1 mRNA increased in liver tissues of patients with progression of fibrosis. Gene expression levels of TLL1 short variants, including isoform 2, were higher in patients with rs17047200 AT/TT. Conclusions In a GWAS, we identified the association between the SNP rs17047200, within the intron of TLL1 , and development of HCC in patients who achieved an SVR to treatment for chronic HCV infection. We found levels of Tll1/TLL1 mRNA to be increased in rodent models of liver injury and liver tissues of patients with fibrosis, compared with controls. We propose that this SNP might affect splicing of TLL1 mRNA, yielding short variants with high catalytic activity that accelerates hepatic fibrogenesis and carcinogenesis. Further studies are needed to determine how rs17047200 affects TLL1 mRNA levels, splicing, and translation, as well as the prevalence of this variant among other patients with HCC. Tests for the TLL1 SNP might be used to identify patients at risk for HCC after an SVR to treatment of HCV infection.
- Published
- 2016
44. Up‐regulated aldo‐keto reductase family 1 member B10 in chronic hepatitis C: association with serum alpha‐fetoprotein and hepatocellular carcinoma
- Author
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Hironori Tsuzura, Takuya Genda, Yoshio Kanemitsu, Tetsu Kikuchi, Katsuyori Iijima, Katsuharu Hirano, Yutaka Narita, Ryo Wada, Shunsuke Sato, and Takafumi Ichida
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,Carcinoma, Hepatocellular ,Cirrhosis ,Hepatitis C virus ,Aldo-Keto Reductases ,liver ,Chronic liver disease ,medicine.disease_cause ,Gastroenterology ,Gene Expression Regulation, Enzymologic ,alpha-fetoprotein ,AKR1B10 ,Aldehyde Reductase ,Risk Factors ,Internal medicine ,Clinical Studies ,Biomarkers, Tumor ,medicine ,chronic hepatitis C ,Humans ,neoplasms ,Aged ,Oligonucleotide Array Sequence Analysis ,Hepatology ,business.industry ,Gene Expression Profiling ,Liver Neoplasms ,Cancer ,Hepatitis C ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Immunohistochemistry ,digestive system diseases ,Up-Regulation ,risk factor ,Case-Control Studies ,Hepatocellular carcinoma ,Female ,alpha-Fetoproteins ,Alpha-fetoprotein ,Viral hepatitis ,business ,carcinogenesis ,microarray - Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide 1. Approximately 70–90% of patients with HCC have an established background of chronic liver disease and cirrhosis 1. Persistent infection with the hepatitis C virus (HCV) is one of the major causes of chronic liver disease leading to the development of HCC. Persistent HCV infection is responsible for 27–75% of the HCC cases in Europe and the United States and >80% of the HCC cases in Japan 2, 3. The annual incidence of HCC development is 2–8% in cirrhotic patients with chronic HCV infection 4, 5. Persons with anti-HCV positivity were shown to have a 20-fold increased risk of developing HCC in comparison with those who were negative for anti-HCV 6. Thus, the carcinogenic role of persistent HCV infection appears to be significant. However, the molecular mechanism of HCV-related hepatocarcinogenesis is not completely understood, particularly in its early stages. Alpha-fetoprotein (AFP) is the most thoroughly characterized carcinofetal gene product and its usefulness in the surveillance and diagnosis of HCC is well established. On the other hand, AFP elevation is recognized not only in patients with HCC but also in patients with chronic viral hepatitis or cirrhosis, who have no evidence of HCC. AFP elevation was observed in over 15% of patients with chronic hepatitis C in the absence of HCC 7. In addition, several studies have indicated that AFP elevation is a significant predictor of HCC development 8–10. Recent reports reveal that the estimated HCC risk in patients with elevated AFP is over three-fold higher than that in patients with normal AFP 11, 12. These observations suggest that the molecular alterations associated with the very early stages of hepatocarcinogenesis have occurred in the livers of patients with chronic hepatitis C with AFP elevation. In this study, we attempted to identify a specific gene expression signature by performing microarray analysis on the livers of patients with chronic hepatitis C and AFP elevation, which is considered high risk for development of HCC.
- Published
- 2012
45. Effects of endoscopic papillary balloon dilation and endoscopic sphincterotomy on bacterial contamination of the biliary tract
- Author
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Masaaki Natsui, Hiroto Nakadaira, Takuya Genda, and Terasu Honma
- Subjects
Male ,medicine.medical_specialty ,Bile Duct Diseases ,Gastroenterology ,Catheterization ,law.invention ,Sphincterotomy, Endoscopic ,Randomized controlled trial ,Cholelithiasis ,law ,Internal medicine ,Sphincter of Oddi ,Cholecystitis ,medicine ,Bile ,Humans ,In patient ,Endoscopy, Digestive System ,Aged ,Aged, 80 and over ,Cholangiopancreatography, Endoscopic Retrograde ,Endoscopic retrograde cholangiopancreatography ,Bacteria ,Hepatology ,medicine.diagnostic_test ,business.industry ,Significant difference ,Middle Aged ,Surgery ,Treatment Outcome ,Biliary tract ,Balloon dilation ,Female ,Ultrasonography ,Epidemiologic Methods ,business - Abstract
Background and study aims Although endoscopic papillary balloon dilation (EPBD) has appeared with the expectation of better preserving sphincter of Oddi function than endoscopic sphincterotomy (EST), whether it can more effectively prevent bacterial contamination of the biliary tract than EST is controversial. To address this issue, we investigated the bacterial flora in the bile after the two procedures. Patients and methods Eighty-six patients were alternately allocated to EPBD or EST. Blood-liver function tests, ultrasonography, and endoscopic retrograde cholangiopancreatography were performed 6 months and 2 years after EPBD or EST, and the bile was sampled for bacterial culture during endoscopic retrograde cholangiopancreatography. Bactobilia and late complications were prospectively compared between the two procedures. Results Overall, no significant difference was found in the incidence of bactobilia between EPBD and EST at the two examination points. Limiting stone diameter to 8 mm or less, there was a trend toward lower rate of bactobilia in the EPBD group 2 years later although the statistical significance disappeared after correction for multiple comparisons. The absence rate of late complications after EPBD was higher than that after EST, but there was no significant difference between the two procedures, both for the overall patients and for the patients with small stones. Conclusion EPBD has a possibility of suppressing bacterial contamination of the biliary tract compared with EST in patients with small stones. A large, long-term follow-up, randomized, controlled trial is necessary to clarify whether this benefit of EPBD reduces late complications.
- Published
- 2011
46. Ledipasvir and sofosbuvir fixed-dose combination with and without ribavirin for 12 weeks in treatment-naive and previously treated Japanese patients with genotype 1 hepatitis C: an open-label, randomised, phase 3 trial
- Author
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Masaaki Korenaga, Kunio Nakane, John G. McHutchison, Yoshiyuki Ueno, Masa Omote, Tatsuya Ide, Mikio Yanase, Steven J. Knox, Bing Gao, Kazushige Nirei, Tetsuo Takehara, Namiki Izumi, Osamu Yokosuka, Kim Garrison, Masao Omata, Hiroshi Yatsuhashi, William T. Symonds, Juan Betular, Hitoshi Mochizuki, Hidenori Toyoda, Hirayuki Enomoto, Takuya Genda, Fusao Ikeda, Takeji Umemura, Nobuo Toda, Akinobu Ishizaki, Phillip S. Pang, Masashi Mizokami, Yoichi Nishigaki, Naoya Sakamoto, and Hongmei Mo
- Subjects
Ledipasvir ,Adult ,Male ,medicine.medical_specialty ,Time Factors ,Sofosbuvir ,Drug-Related Side Effects and Adverse Reactions ,Genotype ,Hepatitis C virus ,Population ,Administration, Oral ,Hepacivirus ,medicine.disease_cause ,Gastroenterology ,Antiviral Agents ,chemistry.chemical_compound ,Young Adult ,Asian People ,Japan ,Internal medicine ,Ribavirin ,medicine ,Humans ,education ,Aged ,Aged, 80 and over ,education.field_of_study ,Fluorenes ,business.industry ,Hepatitis C ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Surgery ,Infectious Diseases ,Treatment Outcome ,chemistry ,Tolerability ,Asunaprevir ,Benzimidazoles ,Female ,business ,Uridine Monophosphate ,medicine.drug - Abstract
Summary Background Compared with other countries, patients with chronic hepatitis C infection in Japan tend to be older, have more advanced liver disease, and are more likely to have been previously treated for hepatitis C. We aimed to assess the efficacy and safety of an all-oral, fixed-dose combination of the hepatitis C virus NS5A inhibitor ledipasvir and the NS5B nucleotide polymerase inhibitor sofosbuvir with and without ribavirin for 12 weeks in treatment-naive and previously treated Japanese patients with chronic genotype 1 hepatitis C virus infection. Methods In this randomised, open-label study, we enrolled patients from 19 clinical Japanese centres. Patients were randomly assigned (1:1) to receive either ledipasvir (90 mg) and sofosbuvir (400 mg) or ledipasvir, sofosbuvir, and ribavirin (dosed according to the Japanese Copegus product label—ie, patients ≤60 kg received 600 mg daily, patients >60 kg to ≤80 kg received 800 mg daily, and patients >80 kg received 1000 mg daily) orally once daily for 12 weeks. After completion or early discontinuation of treatment, patients were followed up off-treatment for 24 weeks. Eligible patients were at least 20 years of age with chronic genotype 1 hepatitis C virus infection with serum hepatitis C virus RNA concentrations of at least 5 log 10 IU/mL, creatinine clearance of at least 1·0 mL/s, and a platelet count of at least 50 × 10 9 per L. An interactive web response system was used to manage patient randomisation and treatment assignment. Randomisation was stratified by the presence or absence of cirrhosis for treatment-naive patients and stratified by presence or absence of cirrhosis and by previous treatment category (relapser or breakthrough, non-responder, or interferon-intolerant) for previously treated patients. Within each strata, patients were sequentially assigned to either treatment with ledipasvir-sofosbuvir or ledipasvir-sofosbuvir plus ribavirin in a 1:1 ratio with block size of 4. The primary endpoint was sustained virological response 12 weeks after completion of treatment (SVR12) assessed in all patients who were randomly assigned and received at least one dose of study drug; safety outcomes were assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT01975675. Findings Between Oct 15, 2013 and Dec 13, 2013, 341 patients were randomly assigned to treatment groups and received at least one dose of study treatment. SVR12 was achieved in all 171 (100%) patients (83 of 83 treatment naive and 88 of 88 treatment experienced) receiving ledipasvir-sofosbuvir (95% CI 98–100) and 167 (98%) of 170 patients (80 of 83 treatment naive and 87 of 87 treatment experienced) receiving ledipasvir-sofosbuvir plus ribavirin (95% CI 95–100). Of the 76 patients with baseline NS5A resistant variants, 75 (99%) achieved SVR12. Two (1·2%) of 170 patients in the ledipasvir-sofosbuvir plus ribavirin group discontinued treatment because of adverse events. The most common adverse events were nasopharyngitis (50 [29·2%] of 171), headache (12 [7·0%] of 171), and malaise (nine [5·3%] of 171) in patients receiving ledipasvir-sofosbuvir; and nasopharyngitis (40 [23·5%] of 170), anaemia (23 [13·5%] of 170), and headache in those receiving ledipasvir-sofosbuvir and ribavirin (15 [8·8%] of 170). Interpretation Although existing regimens for the treatment of hepatitis C virus are effective for many patients, medical needs remain unmet, particularly in Japan where the population with hepatitis C virus genotype 1 is generally older and treatment-experienced, with advanced liver disease. The efficacy, tolerability, and absence of drug–drug interactions of ledipasvir-sofosbuvir suggest that it could be an important option for treatment of genotype 1 hepatitis C virus in Japanese patients. Funding Gilead Sciences.
- Published
- 2015
47. Mo1265 Significance of atrophic Changes of Gastric Mucosa in Patients With Gastric Mucosal Injury in Low-Dose Aspirin Users
- Author
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Akihito Nagahara, Mariko Hojo, Yuji Shimada, Katsuyori Iijima, Yutaka Narita, Daisuke Asaoka, Sumio Watanabe, Hironori Tuzura, Kentaro Izumi, Takuya Genda, Shunsuke Sato, Ayato Murata, Yoshio Kanemitsu, and Masato Kamei
- Subjects
medicine.medical_specialty ,medicine.anatomical_structure ,Hepatology ,business.industry ,Internal medicine ,Gastroenterology ,medicine ,Gastric mucosa ,In patient ,business ,Low dose aspirin - Published
- 2016
48. Sustained virologic response by ledipasvir/sofosbuvir reduces the incidence of hepatocellular carcinoma in Japanese patients with HCV genotype 1 infection. - Comparison with Simeprevir with peginterferon plus ribavirin
- Author
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Mikio Yanase, Tatsuya Ide, Masao Omata, H. Toyota, Nobuo Toda, Shuhei Nishiguchi, Osamu Yokosuka, Takeji Umemura, Fusao Ikeda, Takuya Genda, Masashi Mizokami, Masaaki Korenaga, Hiroshi Yatsuhashi, Y. Nishigaki, Naoya Sakamoto, Yoshiyuki Ueno, Tetsuo Takehara, Kazushige Nirei, and Namiki Izumi
- Subjects
Simeprevir ,medicine.medical_specialty ,Hepatology ,business.industry ,Ribavirin ,Incidence (epidemiology) ,010102 general mathematics ,medicine.disease ,01 natural sciences ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Hcv genotype 1 ,chemistry ,Hepatocellular carcinoma ,Virologic response ,Internal medicine ,Medicine ,LEDIPASVIR/SOFOSBUVIR ,030212 general & internal medicine ,0101 mathematics ,business - Published
- 2017
49. Liver Transplantation for Primary Biliary Cirrhosis
- Author
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Takafumi Ichida and Takuya Genda
- Subjects
Prognosis prediction ,medicine.medical_specialty ,Cirrhosis ,business.industry ,medicine.medical_treatment ,Treatment method ,Liver transplantation ,medicine.disease ,Gastroenterology ,digestive system diseases ,Ursodeoxycholic acid ,Transplantation ,surgical procedures, operative ,Primary biliary cirrhosis ,Internal medicine ,medicine ,Adult liver ,skin and connective tissue diseases ,business ,medicine.drug - Abstract
Primary biliary cirrhosis (PBC) is one of the most common indications for adult liver transplantation in both Western countries and Japan. Recently, the number of liver transplantations for PBC has shown a decreasing trend in Europe and the United States, likely due to advances in medical therapies using ursodeoxycholic acid. However, liver transplantation remains the sole life-saving treatment method for PBC that has progressed to end-stage cirrhosis. Additionally, liver transplantation is occasionally indicated due to declines in the quality of life arising from severe cutaneous pruritus or chronic fatigue in PBC patients. The appropriate timing of the transplantation is calculated using several different prognosis prediction models. The results of liver transplantations for PBC have been excellent compared with those for other diseases, with all studies reporting 5-year survival rates higher than 70 %. Moreover, differences have not been observed between the results of transplants from living donors and those from deceased donors. PBC can recur in the graft liver after transplantation, but this phenomenon is poorly understood, including its frequency, risk factors, and long-term prognosis.
- Published
- 2014
50. Prediction of Hepatocellular Carcinoma Development after Hepatitis C Virus Eradication Using Serum Wisteria floribunda Agglutinin-Positive Mac-2-Binding Protein
- Author
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Ryo Wada, Yuji Shimada, Nozomi Amano, Yutaka Narita, Akihito Nagahara, Katsuyori Iijima, Shunsuke Sato, Takuya Genda, Takafumi Ichida, Sumio Watanabe, Sho Sato, Ayato Murata, Katsuharu Hirano, Hironori Tsuzura, and Yoshio Kanemitsu
- Subjects
Male ,Receptors, N-Acetylglucosamine ,Hepacivirus ,medicine.disease_cause ,Gastroenterology ,Polyethylene Glycols ,lcsh:Chemistry ,0302 clinical medicine ,Risk Factors ,WFA+-M2BP ,hepatocellular carcinoma ,chronic hepatitis C ,risk factor ,sustained virological response ,Fibrosis ,Interferon ,Cumulative incidence ,lcsh:QH301-705.5 ,Spectroscopy ,Aged, 80 and over ,Membrane Glycoproteins ,biology ,Liver Neoplasms ,Hazard ratio ,General Medicine ,Middle Aged ,Wisteria floribunda ,Recombinant Proteins ,Computer Science Applications ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Drug Therapy, Combination ,Female ,030211 gastroenterology & hepatology ,Plant Lectins ,Mac 2 binding protein ,Protein Binding ,medicine.drug ,Adult ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Hepatitis C virus ,Article ,Catalysis ,Inorganic Chemistry ,Young Adult ,03 medical and health sciences ,Antigens, Neoplasm ,Internal medicine ,Ribavirin ,medicine ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,Aged ,Retrospective Studies ,business.industry ,Organic Chemistry ,Interferon-alpha ,Hepatitis C, Chronic ,biology.organism_classification ,medicine.disease ,digestive system diseases ,lcsh:Biology (General) ,lcsh:QD1-999 ,Immunology ,business - Abstract
We aimed to clarify the association between a novel serum fibrosis marker, Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP), and hepatocellular carcinoma (HCC) development in 355 patients with chronic hepatitis C who achieved sustained virologic response (SVR) through interferon-based antiviral therapy. Pretreatment serum WFA+-M2BP levels were quantified and the hazard ratios (HRs) for HCC development were retrospectively analyzed by Cox proportional hazard analysis. During the median follow-up time of 2.9 years, 12 patients developed HCC. Multivariate analysis demonstrated that high serum WFA+-M2BP (≥2.80 cut off index (COI), HR = 15.20, p = 0.013) and high fibrosis-4 (FIB-4) index (≥3.7, HR = 5.62, p = 0.034) were independent risk factors for HCC development. The three- and five-year cumulative incidence of HCC in patients with low WFA+-M2BP were 0.4% and 0.4%, respectively, whereas those of patients with high WFA+-M2BP were 7.7% and 17.6%, respectively (p < 0.001). In addition, combination of serum WFA+-M2BP and FIB-4 indices successfully stratified the risk of HCC: the five-year cumulative incidences of HCC were 26.9%, 6.8%, and 0.0% in patients with both, either, and none of these risk factors, respectively (p < 0.001). In conclusion, pretreatment serum WFA+-M2BP level is a useful predictor for HCC development after achieving SVR.
- Published
- 2016
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