204 results on '"Kazuharu Suzuki"'
Search Results
2. Effects of activation of an alcohol metabolic gene, cigarette smoking, and alcohol intake on the incidence of metachronous gastric cancer in patients who underwent endoscopic resection for gastric cancer: A multicenter retrospective pilot study
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Satoshi Abiko, Yuichi Shimizu, Marin Ishikawa, Masaki Inoue, Katsuma Nakajima, Risako Kohya, Koji Hirata, Kazuharu Suzuki, Ryo Sugiura, Shuichi Miyamoto, Kenji Kinoshita, Kazuteru Hatanaka, Yoshiya Yamamoto, Hirohito Naruse, Takuto Miyagishima, and Naoya Sakamoto
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alcohol dehydrogenase‐1B ,aldehyde dehydrogenase‐2 ,cigarette smoking ,endoscopic resection ,gastric cancer ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Background and Aim Metachronous gastric cancer (GC) frequently occurs in patients who have undergone endoscopic resection (ER) for GC. We evaluated the risk for development of metachronous GC following ER for GC based on genetic polymorphisms for alcohol dehydrogenase‐1B (ADH1B) and aldehyde dehydrogenase‐2 (ALDH2), as well as alcohol consumption and smoking habits. Methods We studied 77 patients who underwent ER for GC (median follow‐up of 84 months). Genotyping of ADH1B/ALDH2 was performed using saliva sampling. Histories of alcohol consumption and smoking before and after ER and Helicobacter pylori eradication were documented. Results Multivariate analyses revealed that homozygous slow‐metabolizing ADH1B (hazard ratio [HR] = 2.38, P
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- 2023
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3. Serum IL-1β predicts de novo hepatitis B virus reactivation during direct-acting antiviral therapy for hepatitis C, not during anti-cancer/immunosuppressive therapy
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Naoki Kawagishi, Goki Suda, Ryotaro Sakamori, Takeshi Matsui, Masahiro Onozawa, Zijian Yang, Sonoe Yoshida, Masatsugu Ohara, Megumi Kimura, Akinori Kubo, Osamu Maehara, Qingjie Fu, Shunichi Hosoda, Yoshimasa Tokuchi, Kazuharu Suzuki, Masato Nakai, Takuya Sho, Kenichi Morikawa, Mitsuteru Natsuizaka, Koji Ogawa, Hajime Sakai, Shunsuke Ohnishi, Masaru Baba, Tetsuo Takehara, and Naoya Sakamoto
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Medicine ,Science - Abstract
Abstract De novo hepatitis B virus (HBV) reactivation occurs during direct-acting antiviral (DAA) treatment in hepatitis C virus (HCV)-infected patients with resolved HBV infection. We evaluated the predictive factors, mechanical insight, and differences of cytokine levels during anti-cancer/immunosuppressive and DAA. Eleven, 35, and 19 HCV-infected patients with previous HBV infection with HBV reactivation during DAA treatment, previous HBV infection without HBV reactivation during DAA treatment, and without HBV infection resolution receiving DAA treatment, respectively, were enrolled. Clinical data and baseline cytokine levels were analyzed. Low baseline serum interleukin (IL)-1β levels predicted de novo HBV reactivation during DAA treatment (odds ratio: 47.6, 95% confidence interval: 6.94–333.3). HCV-infected patients with the IL-1β gene single nucleotide polymorphism rs16944 AA allele had significantly higher IL-1β levels; no HCV-infected patient with the IL-1β AA allele experienced HBV reactivation during DAA treatment. Compared to HCV-infected patients with HBV infection resolution, non-HCV infected patients with or without HBV reactivation during anti-cancer/immunosuppressive therapy or bone marrow transplantation had remarkably lower baseline IL-1β levels. Low IL-1β levels were not associated with HBV reactivation. IL-1β levels before DAA for HCV-infected patients with resolved HBV infection could predict HBV reactivation during DAA treatment.
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- 2022
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4. Prediction of hepatocellular carcinoma using age and liver stiffness on transient elastography after hepatitis C virus eradication
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Masato Nakai, Yoshiya Yamamoto, Masaru Baba, Goki Suda, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Ren Yamada, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Ken Furuya, and Naoya Sakamoto
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Medicine ,Science - Abstract
Abstract Liver stiffness measurement (LSM) is a useful tool for assessing advanced liver fibrosis, an important risk factor for hepatocellular carcinoma (HCC) following hepatitis C (HCV) eradication. This study aimed to clarify the non-invasive factors associated with HCC following sustained virological response (SVR) and to identify the low-risk group. 567 patients without history of HCC who achieved SVR at 24 weeks (SVR24) after IFN-free treatment were retrospectively analyzed. The cumulative incidence of HCC and the risk factors were examined using pre-treatment and SVR24 data. The median observation period was 50.2 months. Thirty cases of HCC were observed, and the 4-year cumulative incidence of HCC was 5.9%. In multivariate analysis, significant pre-treatment factors were age ≥ 71 years (hazard ratio [HR]: 3.402) and LSM ≥ 9.2 kPa (HR: 6.328); SVR24 factors were age ≥ 71 years (HR: 2.689) and LSM ≥ 8.4 kPa (HR: 6.642). In cases with age
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- 2022
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5. Possible correlation between increased serum free carnitine levels and increased skeletal muscle mass following HCV eradication by direct acting antivirals
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Yoshimasa Tokuchi, Goki Suda, Megumi Kimura, Osamu Maehara, Takashi Kitagataya, Akinori Kubo, Sonoe Yoshida, Qingjie Fu, Zijian Yang, Shunichi Hosoda, Masatsugu Ohara, Ren Yamada, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Shunsuke Ohnishi, and Naoya Sakamoto
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Medicine ,Science - Abstract
Abstract We aimed to evaluate factors associated with changes in skeletal muscle mass in hepatitis C virus (HCV)-infected patients after treatment with direct-acting antivirals (DAAs). Consecutive HCV-infected patients after treatment with DAA were recruited into the study. Patients who achieved sustained virological response (SVR); and had complete clinical information, preserved serum samples at baseline and SVR48, and skeletal muscle mass evaluations based on the psoas muscle mass index (PMI) on computed tomography at baseline and ≥ 12 months were included. Altogether, 70.7% of patients (41/58) showed increased PMI after DAA therapy, and mean relative PMI was significantly higher after DAA therapy than at baseline. There were no significant associations between baseline clinical factors routinely examined in clinical practice and increased PMI. Among factors reported to be associated with skeletal muscle loss in patients with chronic liver disease, serum zinc levels and total and free carnitine levels increased significantly after DAA therapy and only changes in serum free carnitine levels were significantly associated with an increased PMI (r = 0305, P = 0.020). In conclusion, increased skeletal muscle mass after successful HCV eradication by DAAs was significantly associated with increased serum-free carnitine levels. l-carnitine supplementation may be beneficial in patients with low skeletal muscle mass after DAA.
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- 2021
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6. Low baseline CXCL9 predicts early progressive disease in unresectable HCC with atezolizumab plus bevacizumab treatment
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Shunichi Hosoda, Goki Suda, Takuya Sho, Koji Ogawa, Megumi Kimura, Zijian Yang, Sonoe Yoshida, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Osamu Maehara, Shunsuke Ohnishi, Akihisa Nakamura, Ren Yamada, Masatsugu Ohara, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kenichi Morikawa, Ken Furuya, Masaru Baba, Yoshiya Yamamoto, Kazuharu Suzuki, Takaaki Izumi, Takashi Meguro, Katsumi Terashita, Jun Ito, Takuto Miyagishima, and Naoya Sakamoto
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: Atezolizumab plus bevacizumab treatment is highly effective in patients with unresectable hepatocellular carcinoma (HCC). However, progressive disease (PD) occurs in approximately 20% of HCC patients treated with atezolizumab plus bevacizumab, resulting in a poor prognosis. Thus, the prediction and early detection of HCC is crucial. Methods: Patients with unresectable HCC treated with atezolizumab plus bevacizumab and had baseline preserved serum (n = 68) were screened and classified according to their PD, six weeks after treatment initiation (early PD; n = 13). Of these, four patients each with and without early PD were selected for cytokine array and genetic analyses. The identified factors were validated in the validated cohort (n = 60) and evaluated in patients treated with lenvatinib. Results: No significant differences were observed in the genetic alterations in circulating tumor DNA. Cytokine array data revealed that baseline MIG (CXCL9), ENA-78, and RANTES differed substantially between patients with and without early PD. Subsequent analysis in the validation cohort revealed that baseline CXCL9 was significantly lower in patients with early PD than that in patients without early PD, and the best cut-off value of serum CXCL9 to predict early PD was 333 pg/mL (sensitivity: 0.600, specificity: 0.923, AUC = 0.75). In patients with lower serum CXCL9 (< 333 pg/mL), 35.3% (12/34) experienced early PD with atezolizumab plus bevacizumab, while progression-free survival (PFS) was significantly shorter relative to that in patients without (median PFS, 126 days vs 227 days; HR: 2.41, 95% CI: 1.22–4.80, p = 0.0084). While patients with objective response to lenvatinib had significantly lower CXCL9 levels compared with those of patients without. Conclusion: Baseline low serum CXCL9 (< 333 pg/mL) levels may predict early PD in patients with unresectable HCC treated with atezolizumab plus bevacizumab.
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- 2022
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7. Case Report: Hereditary Fibrosing Poikiloderma With Tendon Contractures, Myopathy, and Pulmonary Fibrosis (POIKTMP) Presenting With Liver Cirrhosis and Steroid-Responsive Interstitial Pneumonia
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Michiko Takimoto-Sato, Toshinari Miyauchi, Masaru Suzuki, Hideyuki Ujiie, Toshifumi Nomura, Tomoo Ikari, Tomohiko Nakamura, Kei Takahashi, Machiko Matsumoto-Sasaki, Hirokazu Kimura, Hiroki Kimura, Yuichiro Matsui, Takashi Kitagataya, Ren Yamada, Kazuharu Suzuki, Akihisa Nakamura, Masato Nakai, Takuya Sho, Koji Ogawa, Naoya Sakamoto, Naoko Yamaguchi, Noriyuki Otsuka, Utano Tomaru, and Satoshi Konno
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POIKTMP ,FAM111B ,interstitial pneumonia ,liver cirrhosis ,case report ,Genetics ,QH426-470 - Abstract
Background: Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is an extremely rare disease caused by mutations in FAM111B, and only approximately 30 cases have been reported worldwide. Some patients develop interstitial pneumonia, which may lead to progressive pulmonary fibrosis and poor prognosis. However, no effective treatment for interstitial pneumonia associated with POIKTMP has been reported. Here, we report an autopsy case of POIKTMP, wherein interstitial pneumonia was improved by corticosteroids.Case Presentation: A 44-year-old Japanese man was referred to our hospital due to poikiloderma, hypotrichosis, and interstitial pneumonia. He developed progressive poikiloderma and muscle weakness since infancy. He also had tendon contractures, short stature, liver cirrhosis, and interstitial pneumonia. Mutation analysis of FAM111B revealed a novel and de novo heterozygous missense mutation, c.1886T > G (p(Phe629Cys)), through which we were able to diagnose the patient with POIKTMP. 3 years after the POIKTMP diagnosis, interstitial pneumonia had worsened. After 2 weeks of administrating 40 mg/day of prednisolone, his symptoms and lung shadows improved. However, he subsequently developed severe hepatic encephalopathy and eventually died of respiratory failure due to bacterial pneumonia and pulmonary edema. Autopsy revealed an unclassifiable pattern of interstitial pneumonia, as well as the presence of fibrosis and fatty degeneration in several organs, including the liver, kidney, skeletal muscle, heart, pancreas, and thyroid.Conclusions: We report a case of POIKTMP in which interstitial pneumonia was improved by corticosteroids, suggesting that corticosteroids could be an option for the treatment of interstitial pneumonia associated with this disease.
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- 2022
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8. Baseline elevated serum angiopoietin-2 predicts long-term non-regression of liver fibrosis after direct-acting antiviral therapy for hepatitis C
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Naoki Kawagishi, Goki Suda, Megumi Kimura, Osamu Maehara, Ren Yamada, Yoshimasa Tokuchi, Akinori Kubo, Takashi Kitagataya, Taku Shigesawa, Kazuharu Suzuki, Masatsugu Ohara, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Yusuke Kudo, Mutsumi Nishida, and Naoya Sakamoto
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Medicine ,Science - Abstract
Abstract We previously revealed that Angiopoietin-2 (Ang2) predicts non-regression of liver fibrosis based on liver stiffness measurement (LSM) at 24 weeks after anti-hepatitis C virus (HCV) treatment. In this study, we extended the observational period to 96 weeks to investigate the factors associated with non-regression after treatment with direct-acting-antivirals (DAAs). Patients treated with DAAs who underwent transient elastography at baseline and 24 and 96 weeks after DAA therapy were included. Baseline and post-treatment serum Ang2 levels were measured. Liver fibrosis stages were defined based on LSM. Multivariate regression was used to evaluate factors associated with non-regression of liver fibrosis between various time points. In total, 110 patients were included. Of these, 11% showed non-regression of LSM-based fibrosis stage at 96 weeks after DAA therapy. In multivariate analysis, advanced liver fibrosis stage and high baseline Ang2 levels were significantly associated with non-regression at 96 weeks. In patients with advanced liver fibrosis (F3/4), baseline Ang2 levels were associated with non-regression of liver fibrosis stage. Between SVR24 and SVR96, post-treatment Ang2 levels and controlled attenuation parameter values at SVR24 were significantly associated with non-regression of liver fibrosis stage in patients with F3/4. Thus, serum Ang2 levels are an important target for monitoring and therapy.
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- 2021
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9. Baseline angiopoietin‐2 and FGF19 levels predict treatment response in patients receiving multikinase inhibitors for hepatocellular carcinoma
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Taku Shigesawa, Goki Suda, Megumi Kimura, Tomoe Shimazaki, Osamu Maehara, Ren Yamada, Takashi Kitagataya, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Machiko Umemura, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, and Naoya Sakamoto
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angiopoietin‐2 ,fibroblast growth factor 19 ,hepatocellular carcinoma ,sorafenib ,treatment outcome ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Background Sorafenib and lenvatinib are first‐line systemic therapies for unresectable hepatocellular carcinoma (HCC). However, the criteria for their selection remain unclear. Methods We identified patients with unresectable HCC who were treated with sorafenib or lenvatinib between August 2009 and January 2019 at the Hokkaido University Hospital. Patients who continued treatment for >2 months, underwent evaluation by computed tomography every 2–3 months, and had complete clinical data were included. Responders were patients with objective response (OR) for lenvatinib and patients with stable disease (SD) exceeding 6 months (long‐SD) or OR for sorafenib. The predictive factors for treatment response, including fibroblast growth factor (FGF)19 and 21, angiopoietin 2 (ANG2), hepatocyte growth factor, and vascular endothelial growth factor, were evaluated. Results Overall, 27 and 29 patients treated with lenvatinib and sorafenib, respectively, were included. The responders for lenvatinib and sorafenib were 63% (17/27) and 38% (11/29), respectively. No significant predictive factors for treatment response were identified in patients treated with sorafenib. However, baseline serum FGF19 and ANG2 levels were significantly associated with treatment response to lenvatinib. All (9/9) patients with low baseline ANG2 and FGF19 levels who received lenvatinib achieved OR. Conversely, the OR was low (13%; 1/9) in patients with high baseline ANG2 and FGF19 levels. Responder rate was 40% (2/5) in patients with high baseline ANG2 and FGF19 levels who received sorafenib. Conclusion This study is, to our knowledge, the first to demonstrate that baseline ANG2 and FGF19 levels may aid in selecting optimal systemic therapy for patients with unresectable HCC.
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- 2020
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10. Computed tomography, not bioelectrical impedance analysis, is the proper method for evaluating changes in skeletal muscle mass in liver disease
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Masatsugu Ohara, Goki Suda, Megumi Kimura, Osamu Maehara, Tomoe Shimazaki, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, and Naoya Sakamoto
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Secondary sarcopenia ,Psoas muscle mass index ,BIA ,Computed tomography ,Internal medicine ,RC31-1245 - Abstract
Abstract Background Sarcopenia is associated with poor prognosis in patients with chronic liver disease (CLD). As rapid skeletal muscle wasting predicts worse prognosis and a novel therapy for sarcopenia needs to be evaluated for validation, accurate evaluation methods for relative changes in muscle mass are crucial. Methods We screened CLD patients who had skeletal muscle mass evaluation between June 2015 and December 2017. Patients were included if they had adequate information, were followed for >6 months, and had skeletal muscle mass evaluation by both bioelectrical impedance analysis (BIA) and computed tomography (CT) imaging at baseline and the second evaluation point. We compared BIA and CT imaging in terms of their ability to quantify skeletal muscle mass and identify relative changes in muscle mass in CLD patients. Results Of the screened 447 CLD patients, 110 were included in this study, and 71 (64.5%) were men. The median age was 68 (range 21 to 90) years. In total, 83 (75.5%) and 32 (29.1%) patients had liver cirrhosis and hepatocellular carcinoma, respectively. Of them, 50 (45.5%) patients were liver cirrhosis patients without hepatocellular carcinoma through the observation period. Skeletal muscle mass index (SMI) by BIA, psoas muscle mass index (PMI), and SMI based on CT imaging were significantly correlated at baseline [SMI by simple CT method and SMI by BIA (r = 0.61, P
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- 2020
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11. Early response and safety of lenvatinib for patients with advanced hepatocellular carcinoma in a real‐world setting
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Takuya Sho, Goki Suda, Koji Ogawa, Megumi Kimura, Tomoe Shimazaki, Osamu Maehara, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Machiko Umemura, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kenichi Morikawa, Ken Furuya, Masaru Baba, Yoshiya Yamamoto, Tomoe Kobayashi, Takashi Meguro, Akiyoshi Saga, Takuto Miyagishima, Hideki Yokoo, Toshiya Kamiyama, Akinobu Taketomi, and Naoya Sakamoto
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early response ,lenvatinib ,real world ,REFLECT ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background and Aim Lenvatinib has been recently approved as a first‐line systematic therapy for patients with advanced hepatocellular carcinoma (HCC) based on the results of the phase 3 clinical trial REFLECT. This trial excluded patients with a history of systemic chemotherapy, bile duct invasion, and Child‐Pugh grade B. We aimed to investigate the efficacy and safety of lenvatinib for these patients and in the real‐world setting. Methods Among patients who were administered lenvatinib for advanced HCC between April and October 2018 in Hokkaido University Hospital and related hospitals, we evaluated those who were followed for more than 2 months and whose treatment response was evaluated via dynamic computed tomography at baseline and 2 months after treatment initiation. Meanwhile, patients were excluded if they had decompensated liver cirrhosis, were followed up less than 2 months, or were not evaluated at 2 months. Patients were also stratified according to compliance with the REFLECT inclusion criteria for further analysis. Results A total of 41 patients were included; more than 50% did not meet the REFLECT inclusion criteria. In total, 5 (12.2%), 20 (48.8%), 12 (29.3%), and 4 (9.3%) showed complete response, partial response, stable disease, and progressive disease, respectively. The objective response rate was 61.2%. The objective response rate and disease control rate were similar between patients who did and did not meet the REFLECT inclusion criteria. Moreover, the safety profile was also similar between the two patient groups. Conclusion Lenvatinib showed high early response rate and tolerability in patients with advanced HCC. Favorable outcomes were similarly observed in patients who did not meet the REFLECT inclusion criteria.
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- 2020
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12. Effect of switching from tenofovir disoproxil fumarate to tenofovir alafenamide on lipid profiles in patients with hepatitis B.
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Kazuharu Suzuki, Goki Suda, Yoshiya Yamamoto, Satoshi Abiko, Kenji Kinoshita, Shuichi Miyamoto, Ryo Sugiura, Megumi Kimura, Osamu Maehara, Ren Yamada, Takashi Kitagataya, Taku Shigesawa, Masatsugu Ohara, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, and Naoya Sakamoto
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Medicine ,Science - Abstract
For long-term treatment of hepatitis B virus (HBV) infection, switching from tenofovir-disoproxil-fumarate (TDF) to tenofovir-alafenamide (TAF) may prevent renal dysfunction and bone loss. However, the precise effects of this switch on the blood lipid profile remain to be clarified. This is an important issue as TDF is known to have effects on both low- and high-density lipids. Therefore, our retrospective multi-center study aimed to evaluate the effects of switching from TDF to TAF on the lipid profile of patients with HBV infection. Samples were obtained prior to the switch from TDF to TAF and at 6-12 months after TAF initiation. In some cases, additional samples obtained pre- and post-TDF administration were available for analysis. Serum cholesterol levels, including oxidized-low-density lipoprotein (LDL) and non-high-density lipoprotein-cholesterol (HDL-c), and the rate of dyslipidemia, according to the NCEP-ATP III lipid risk classification, were analyzed. The data from 69 patients were analyzed, including 33 patients with pre- and post-TDF-initiation serum samples. Total cholesterol (T-chol), HDL-c, LDL-c, non-HDL-c, and oxidized LDL levels increased significantly after switching to TAF. With regard to sequential changes pre- to post-TAF, TDF was associated with significantly lower serum T-chol, HDL-c, and oxidized LDL-c levels, with T-chol, HDL-c, LDL-c, and oxidized LDL-c levels increasing significantly after the switch. The switch from TDF to TAF was also associated with an increase in the rate of dyslipidemia, from 33% to 39%, with an increase in the rate of severe dyslipidemia of 1.4% and 5.8%, based on T-chol and LDL-c levels. Of note, no cases of severe dyslipidemia were detected pre-TAF treatment. As oxidized LDL-c and non-HDL-c are strongly associated with atherosclerosis development, careful monitoring of lipid is needed after switching from TDF to TAF in this clinical population.
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- 2022
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13. Serum Angiopoietin-2 Predicts the Occurrence and Recurrence of Hepatocellular Carcinoma after Direct-Acting Antiviral Therapy for Hepatitis C
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Naoki Kawagishi, Goki Suda, Yoshiya Yamamoto, Masaru Baba, Ken Furuya, Osamu Maehara, Shunsuke Ohnishi, Sonoe Yoshida, Qingjie Fu, Zijian Yang, Shunichi Hosoda, Yoshimasa Tokuchi, Takashi Kitagataya, Masatsugu Ohara, Kazuharu Suzuki, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Koji Ogawa, and Naoya Sakamoto
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hepatitis C virus ,direct-acting antiviral ,angiopoietin-2 ,hepatocellular carcinoma ,recurrence ,Microbiology ,QR1-502 - Abstract
Progressive liver fibrosis after anti-HCV treatment is a risk factor for HCC. Angiopoietin-2 (Ang2) is associated with non-regression of liver fibrosis after direct-acting antiviral (DAA). This study evaluated the predictive value of serum Ang2 levels for HCC occurrence or recurrence after DAA administration. In this retrospective study, 310 HCV-infected patients treated with DAAs in 2014–2020 were screened and evaluated for HCC occurrence or recurrence every three–six months. Multivariate Cox regression analysis revealed that age ≥ 75 years (HR: 2.92, 95% CI: 1.34–6.33; p = 0.007) and baseline Ang2 level ≥ 464 pg/mL (HR: 2.75, 95% CI: 1.18–6.37; p = 0.019) were significantly associated with HCC occurrence after DAA therapy. A high or low risk of HCC after DAA therapy could be distinguished by the combination of age and baseline Ang2 level. The cumulative incidences of de-novo HCC at two and four years were 0.8% and 3.8% in the low-risk group and 22.6% and 27.1% in the high-risk group, respectively. Baseline Ang2 level ≥ 402 pg/mL was significantly associated with HCC recurrence in patients who achieved sustained virological response with DAAs (HR: 3.68). In conclusion, serum Ang2 levels can predict HCC occurrence and recurrence after successful HCV eradication by DAAs.
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- 2023
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14. Atomic Layer Deposition of Nickel Using a Heteroleptic Ni Precursor with NH3 and Selective Deposition on Defects of Graphene
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Minsu Kim, Shunichi Nabeya, Dip K. Nandi, Kazuharu Suzuki, Hyun-Mi Kim, Seong-Yong Cho, Ki-Bum Kim, and Soo-Hyun Kim
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Chemistry ,QD1-999 - Published
- 2019
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15. Baseline serum angiopoietin-2 and VEGF levels predict the deterioration of the liver functional reserve during lenvatinib treatment for hepatocellular carcinoma.
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Taku Shigesawa, Goki Suda, Megumi Kimura, Osamu Maehara, Yoshimasa Tokuchi, Akinori Kubo, Ren Yamada, Ken Furuya, Masaru Baba, Takashi Kitagataya, Kazuharu Suzuki, Masatsugu Ohara, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, and Naoya Sakamoto
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Medicine ,Science - Abstract
A deteriorated liver functional reserve during systemic therapy for unresectable hepatocellular carcinoma (HCC) causes poor patient outcomes. We aimed to identify predictive factors associated with the deterioration of Child-Pugh score at 8 weeks after lenvatinib initiation. Patients with adequate clinical data and baseline preserved serum samples available were included. Baseline fibroblast growth factor (FGF)19 and 21, angiopoietin (ANG)2, and vascular endothelial growth factor (VEGF) levels were evaluated. Thirty-seven patients were included, and 6, 15, 14, and 2 experienced complete response, partial response, stable disease, and progressive disease, respectively. Twenty-four (65%) and 13 (35%) patients showed a maintained/improved and deteriorated Child-Pugh-score, respectively. While baseline clinical data, treatment response, and laboratory data were similar between these two patient groups, baseline ANG2 and VEGF levels were significantly higher (P = 0.0017) and lower (P = 0.0231), respectively, in patients with deteriorated Child-Pugh score than in those without. Based on receiver operating characteristic curve analysis, cut-off values for ANG2 and VEGF were found to be 3,108 pg/mL and 514.9 pg/mL, respectively. Among patients with low VEGF and high ANG2, 89% (8/9) exhibited a deteriorated Child-Pugh score, whereas none of the patients (0/9) with high VEGF and low ANG2 did. The deterioration of the Child-Pugh score in patients with unresectable HCC who are treated with lenvatinib may be predictable based on combined baseline serum ANG2 and VEGF levels.
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- 2021
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16. L‐Carnitine Suppresses Loss of Skeletal Muscle Mass in Patients With Liver Cirrhosis
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Masatsugu Ohara, Koji Ogawa, Goki Suda, Megumi Kimura, Osamu Maehara, Tomoe Shimazaki, Kazuharu Suzuki, Akihisa Nakamura, Machiko Umemura, Takaaki Izumi, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Shunsuke Ohnishi, and Naoya Sakamoto
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Liver cirrhosis (LC) is a major cause of secondary sarcopenia. Sarcopenia makes the prognosis worse; thus, novel therapeutic options for sarcopenia in patients with LC are urgently required as they are currently limited. In this retrospective study, 158 patients with LC were screened, and 35 of those patients who were treated with L‐carnitine for more than 6 months and for whom skeletal muscle mass changes could be evaluated by computer tomography were enrolled. Of the 158 patients, 79 patients who did not receive L‐carnitine supplementation served as controls. Cases and controls were propensity score matched for age, sex, presence of hepatocellular carcinoma, and branched chain amino acid administration, and changes in skeletal muscle mass and clinical data were compared. The 35 patients who received L‐carnitine supplementation and 35 propensity score‐matched patients who did not receive carnitine supplementation comprised the final enrollment. Compared with control patients, patients who received L‐carnitine had significantly worse liver function, which is associated with rapid progress of skeletal muscle depletion. However, loss of skeletal muscle mass was significantly suppressed in patients receiving L‐carnitine, and a significant effect was observed in patient subgroups stratified by age, sex, presence of hepatocellular carcinoma, and branched chain amino acid administration. The change ratios of most laboratory data, including vitamin D and insulin‐like growth factor 1 levels, were similar in the two groups, but ammonia levels were significantly less in those receiving L‐carnitine. However, even in patients receiving L‐carnitine but not showing an ammonia decrease, loss of skeletal muscle was significantly suppressed. Conclusion: L‐carnitine suppresses loss of skeletal muscle mass and may therefore be a novel therapeutic option for sarcopenia in patients with LC. (Hepatology Communications 2018; 00:000‐000)
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- 2018
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17. Frequency and Characteristics of Overestimated Renal Function in Japanese Patients with Chronic Liver Disease and Its Relation to Sarcopenia
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Sonoe Yoshida, Goki Suda, Masatsugu Ohara, Qingjie Fu, Zijian Yang, Shunichi Hosoda, Megumi Kimura, Kubo Akinori, Yoshimasa Tokuchi, Ren Yamada, Takashi Kitagataya, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Osamu Maehara, Shunsuke Ohnishi, and Naoya Sakamoto
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liver disease ,sarcopenia ,renal function ,creatinine ,skeletal muscle ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Renal dysfunction and sarcopenia are important prognostic factors in patients with chronic liver disease (CLD). Muscle atrophy can cause the overestimation of renal function based on serum creatinine. However, the frequency of overestimated renal function in Japanese patients with CLD and its relationship with sarcopenia are unclear. In present study, we evaluated the frequency of overestimated renal function, defined as a >20% higher eGFR using creatinine than using cystatin C, in 307 patients with CLD as well as its relationship with indicators of sarcopenia. In total, 24.8% of patients had overestimated renal function. In a multivariate regression analysis, liver cirrhosis (p = 0.004) and psoas muscle mass index (p = 0.049) were significantly associated with overestimated renal function. Loss of skeletal muscle mass was significantly more frequent in both male and female patients with overestimated renal function than without. In males, the loss of muscle strength and rate of sarcopenia, defined as loss of muscle mass and strength, were significantly higher in patients with than without overestimated renal function. The high frequency of overestimated renal function in Japanese patients suggests that indicators of renal function should be carefully considered; furthermore, monitoring and interventions for both renal function and sarcopenia are needed in patients with CLD.
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- 2021
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18. Liver steatosis and dyslipidemia after HCV eradication by direct acting antiviral agents are synergistic risks of atherosclerosis.
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Naoki Kawagishi, Goki Suda, Akinobu Nakamura, Megumi Kimura, Osamu Maehara, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Takaaki Izumi, Machiko Umemura, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Yusuke Kudo, Mutsumi Nishida, Hideaki Miyoshi, and Naoya Sakamoto
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Medicine ,Science - Abstract
AIM:We comprehensively analyzed how hepatitis C virus (HCV) eradication by interferon (IFN)-free direct-acting-antiviral-agents (DAAs) affects liver steatosis and atherogenic risk. METHODS:Patients treated with IFN-free-DAAs who underwent transient elastography before and at 24-weeks post-treatment, including controlled attenuation parameter (CAP), and achieved sustained viral response (SVR) were enrolled. The association between changes in liver steatosis, lipid-metabolism, and genetic and clinical factors was analyzed. RESULTS:A total of 117 patients were included. The mean CAP and low-density lipoprotein cholesterol (LDL-C) levels were significantly elevated at SVR24. However, baseline LDL-C and CAP values were significantly negatively correlated with changes in these values after HCV eradication, indicating that in patients with high baseline values, the values generally decreased after HCV eradication. Mean small-dense LDL-C (sdLDL-C), which has greater atherogenic potential, was significantly elevated only in patients with both dyslipidemia (LDL-C >140 mg/dL) and liver steatosis (CAP >248 dB/m) at SVR24. Those patients had significant higher baseline BMI, LDL-C, and total-cholesterol levels. CONCLUSIONS:Generally, successful HCV eradication by IFN-free-DAAs decreases CAP and LDL-C in patients with high baseline values. However, elevated LDL-C was accompanied with elevated sdLDL-C only in patients with liver steatosis and dyslipidemia at SVR24; therefore, those patients may require closer monitoring.
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- 2018
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19. Effects of High Phosphorus Diet on Bone Metabolism-Related Gene Expression in Young and Aged Mice
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Shinichi Katsumata, Hiroshi Matsuzaki, Rie Katsumata-Tsuboi, Mariko Uehara, and Kazuharu Suzuki
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Nutritional diseases. Deficiency diseases ,RC620-627 - Published
- 2014
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20. Low baseline CXCL9 predicts early progressive disease in unresectable HCC with atezolizumab plus bevacizumab treatment
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Shunichi Hosoda, Goki Suda, Takuya Sho, Koji Ogawa, Megumi Kimura, Zijian Yang, Sonoe Yoshida, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Osamu Maehara, Shunsuke Ohnishi, Akihisa Nakamura, Ren Yamada, Masatsugu Ohara, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kenichi Morikawa, Ken Furuya, Masaru Baba, Yoshiya Yamamoto, Kazuharu Suzuki, Takaaki Izumi, Takashi Meguro, Katsumi Terashita, Jun Ito, Takuto Miyagishima, and Naoya Sakamoto
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Bevacizumab ,Oncology ,Hepatology ,Hepatocellular carcinoma ,Baseline ,CXCL9 ,Early PD ,Atezolizumab ,Prognosis - Abstract
Introduction: Atezolizumab plus bevacizumab treatment is highly effective in patients with unresectable hepatocellular carcinoma (HCC). However, progressive disease (PD) occurs in approximately 20% of HCC patients treated with atezolizumab plus bevacizumab, resulting in a poor prognosis. Thus, the prediction and early detection of HCC is crucial. Methods: Patients with unresectable HCC treated with atezolizumab plus bevacizumab and had baseline preserved serum (n = 68) were screened and classified according to their PD, six weeks after treatment initiation (early PD; n = 13). Of these, four patients each with and without early PD were selected for cytokine array and genetic analyses. The identified factors were validated in the validated cohort (n = 60) and evaluated in patients treated with lenvatinib. Results: No significant differences were observed in the genetic alterations in circulating tumor DNA. Cytokine array data revealed that baseline MIG (CXCL9), ENA-78, and RANTES differed substantially between patients with and without early PD. Subsequent analysis in the validation cohort revealed that baseline CXCL9 was significantly lower in patients with early PD than that in patients without early PD, and the best cut-off value of serum CXCL9 to predict early PD was 333 pg/mL (sensitivity: 0.600, specificity: 0.923, AUC = 0.75). In patients with lower serum CXCL9 (< 333 pg/mL), 35.3% (12/34) experienced early PD with atezolizumab plus bevacizumab, while progression-free survival (PFS) was significantly shorter relative to that in patients without (median PFS, 126 days vs 227 days; HR: 2.41, 95% CI: 1.22–4.80, p = 0.0084). While patients with objective response to lenvatinib had significantly lower CXCL9 levels compared with those of patients without. Conclusion: Baseline low serum CXCL9 (< 333 pg/mL) levels may predict early PD in patients with unresectable HCC treated with atezolizumab plus bevacizumab.
- Published
- 2023
21. Potential Correlation between Changes in Serum FGF21 Levels and Lenvatinib-Induced Appetite Loss in Patients with Unresectable Hepatocellular Carcinoma
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Sakamoto, Risako Kohya, Goki Suda, Masatsugu Ohara, Takashi Sasaki, Tomoka Yoda, Naofumi Sakurai, Sonoe Yoshida, Qingjie Fu, Zijian Yang, Shunichi Hosoda, Osamu Maehara, Shunsuke Ohnishi, Yoshimasa Tokuchi, Takashi Kitagataya, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Koji Ogawa, and Naoya
- Subjects
appetite loss ,FGF21 ,hepatocellular carcinoma ,lenvatinib ,prognosis - Abstract
Lenvatinib, used for unresectable hepatocellular carcinoma (HCC), causes appetite loss, but the underlying mechanisms, clinical impact, and predictive factors have been unclear. The endocrine factor FGF21 modulates appetite and is involved in cachexia. We evaluated the association between FGF21 level changes during lenvatinib treatment for unresectable HCC and appetite loss. Sixty-three eligible unresectable HCC patients who started lenvatinib treatment between 2018 and 2021 were included. We analyzed FGF21 levels at baseline; 1, 2, and 4 weeks after lenvatinib initiation, and before the onset of appetite loss. Grade ≥ 2 lenvatinib-induced appetite loss led to liver functional reserve deterioration at disease progression and a poor prognosis. Baseline characteristics and serum FGF21 levels were similar between patients with and without appetite loss. However, the serum FGF21 change rate increased significantly at 4 weeks post-lenvatinib initiation in patients with grade ≥ 2 appetite loss, as compared to those without appetite loss. Similar significant increases in the serum FGF21 level change rate were observed prior to grade ≥ 2 appetite loss onset. This suggests that changes in FGF21 levels can be used to predict patients with a greater risk of marked appetite loss and provides insights into the mechanisms underlying lenvatinib-induced appetite loss in patients with HCC.
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- 2023
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22. Hepatitis C virus eradication by direct‐acting antivirals causes a simultaneous increase in the prevalence of fatty liver and hyper low‐density lipoprotein cholesterolemia without an increase in body weight
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Yoshimasa Tokuchi, Goki Suda, Naoki Kawagishi, Masatsugu Ohara, Risako Kohya, Takashi Sasaki, Tomoka Yoda, Osamu Maehara, Shunsuke Ohnishi, Akinori Kubo, Sonoe Yoshida, Qingjie Fu, Zijian Yang, Shunichi Hosoda, Takashi Kitagataya, Kazuharu Suzuki, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Koji Ogawa, and Naoya Sakamoto
- Subjects
Infectious Diseases ,Hepatology - Published
- 2023
23. Atomic Layer Deposition of Iridium Using a Tricarbonyl Cyclopropenyl Precursor and Oxygen
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Na-Yeon Park, Minsu Kim, Youn-Hye Kim, Rahul Ramesh, Dip K. Nandi, Tomohiro Tsugawa, Toshiyuki Shigetomi, Kazuharu Suzuki, Ryosuke Harada, Miso Kim, Ki-Seok An, Bonggeun Shong, and Soo-Hyun Kim
- Subjects
General Chemical Engineering ,Materials Chemistry ,General Chemistry - Published
- 2022
24. Prophylactic tenofovir alafenamide for hepatitis B virus reactivation and reactivation‐related hepatitis
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Goki Suda, Masaru Baba, Yoshiya Yamamoto, Takuya Sho, Koji Ogawa, Megumi Kimura, Shunichi Hosoda, Sonoe Yoshida, Akinori Kubo, Qingjie Fu, Zijian Yang, Yoshimasa Tokuchi, Takashi Kitagataya, Osamu Maehara, Shunsuke Ohnishi, Ren Yamada, Masatsugu Ohara, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kenichi Morikawa, Ken Furuya, Kazuharu Suzuki, Takaaki Izumi, Takashi Meguro, Katsumi Terashita, Jun Ito, Tomoe Kobayashi, Izumi Tsunematsu, and Naoya Sakamoto
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Infectious Diseases ,Virology - Abstract
No prospective study on the efficacy of tenofovir alafenamide (TAF), a novel tenofovir prodrug, in preventing HBV reactivation has yet been reported.This multicenter prospective study enrolled HBV-carriers who received TAF to prevent HBV reactivation before antitumor or immunosuppressive therapy, and patients with resolved HBV infection who experienced HBV-reactivation and received TAF to prevent HBV reactivation-related hepatitis. The efficacy of prophylactic TAF in preventing HBV reactivation and HBV reactivation-related hepatitis was evaluated at 6 and 12 months after initiating TAF.Overall, 110 patients were administered TAF to prevent HBV reactivation or HBV reactivation-related hepatitis. Three patients died owing to primary disease, whereas one patient was transferred to another hospital within 6 months after initiating TAF. Seven patients died due to primary disease, and five patients were transferred to another hospital within 12 months after initiating TAF. Therefore, 106 and 94 (77 patients with HBV infection, 17 with previous-HBV infection) patients were evaluated at 6 and 12 months after initiating TAF, respectively. No patient experienced HBV reactivation, HBV reactivation-related hepatitis, or treatment discontinuation due to HBV reactivation or adverse events of TAF after 6 and 12 months.TAF could effectively prevent HBV reactivation and HBV reactivation-related hepatitis. This article is protected by copyright. All rights reserved.
- Published
- 2023
25. Red dichromatic imaging improved the visibility of exposed blood vessels in gastric ulcer induced by endoscopic submucosal dissection– a pilot study
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shuichi miyamoto, Masayoshi Ono, Ryo Sugiura, Masayuki Higashino, Goki Suda, Lisako Kohya, Kazuharu Suzuki, Koji Hirata, Satoshi Abiko, Kenji Kinoshita, Hiromi Hirata, Kazuteru Hatanaka, Yoshiya Yamamoto, Hirohito Naruse, Shoko Ono, and Naoya Sakamoto
- Abstract
Background One of the major complications of gastric endoscopic submucosal dissection (ESD) is delayed bleeding. The treatment of exposed vessels after completed dissection should be effective to avoid delayed bleeding. However, it’s sometimes difficult to detect the detection of exposed blood vessels on ulcers induced by ESD. A recent study reported that red dichromatic imaging (RDI) was useful for detecting exposed vessels. In this study, we aimed to measure the visibility of exposed vessels and the quantitative color difference between the exposed vessels and surrounding tissue on ulcers, as observed using RDI after completed dissection. Methods Sixty-four vessels (14 patients) in gastric ESD-induced ulcers were evaluated using both white light imaging (WLI) and RDI. The Commission Internationale de l’Eclairage 1976 (L*a*b*) color space was used to measure the color difference. The color difference was evaluated by comparing the color values of regions of interest for the point of an exposed vessel and three points surrounding an exposed vessel. The visibility of exposed vessels was evaluated using a visibility scoring system. The primary endpoint was color differences (ΔE) between the exposed vessels and surrounding tissue in each modality. Results The average ΔE values (± SEM) for WLI and RDI were 24.85 (± 1.19) and 31.83(± 1.31), respectively. The ΔE value for RDI was significantly higher than that for WLI (p < 0.01). The visibility score was improved in 54.7% (35/64) of cases. Conclusions The color differences between the exposed vessels and surrounding tissue on gastric ESD-induced ulcers were higher with RDI than with WLI, and RDI improved the visibility of exposed vessels.
- Published
- 2022
26. Successful direct clipping of the bleeding source of a colonic diverticular hemorrhage using the 'long-hood gel-filling' method
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Satoshi Abiko, Koji Hirata, Kazuharu Suzuki, Kenji Kinoshita, Kazuteru Hatanaka, Yoshiya Yamamoto, and Hirohito Naruse
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Gastroenterology - Published
- 2023
27. Hepatocellular Carcinoma Rupture after Introducing Lenvatinib: An Autopsy Case Report
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Risako Kohya, Ryo Sugiura, Yoshiya Yamamoto, Hirohito Naruse, Kazuteru Hatanaka, Kenji Kinoshita, Satoshi Abiko, Shuichi Miyamoto, Kazuharu Suzuki, Hanae Kushibiki, Satoru Munakata, and Norihiko Shimoyama
- Subjects
adverse effect ,autopsy case ,Internal Medicine ,General Medicine ,hepatocellular carcinoma ,lenvatinib - Abstract
Hepatocellular carcinoma (HCC) hemorrhaging/rupture is a rare adverse effect of lenvatinib, and only limited pathological examinations have been reported. This report presents the case of a 69-year-old man who suffered from cardiac arrest and died 7 days after starting lenvatinib treatment for HCC, with an autopsy subsequently performed. Crack and coagulated blood were observed in the largest tumor. Pathologically, the hemorrhaging area was scattered in nearly all of the HCC lesions, regardless of tumor differentiation. This pathological feature is unusual in normal HCC. Thus, it is believed to have been the effect of lenvatinib.
- Published
- 2022
28. Efficacy and Effect on Liver Functional Reserve of Atezolizumab and Bevacizumab for Unresectable Hepatocellular Carcinoma in Patients Who Do Not Meet Eligibility Criteria of IMbrave150
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Takuya Sho, Goki Suda, Yoshiya Yamamoto, Ken Furuya, Masaru Baba, Koji Ogawa, Akinori Kubo, Yoshimasa Tokuchi, Qingjie Fu, Zijian Yang, Megumi Kimura, Takashi Kitagataya, Osamu Maehara, Shunsuke Ohnishi, Akihisa Nakamura, Ren Yamada, Masatsugu Ohara, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kazuharu Suzuki, Takaaki Izumi, Takashi Meguro, Katsumi Terashita, Tomofumi Takagi, Jun Ito, Tomoe Kobayashi, Takuto Miyagishima, and Naoya Sakamoto
- Subjects
atezolizumab ,Cancer Research ,Oncology ,bevacizumab ,eligibility criteria of IMbrave150 ,hepatocellular carcinoma - Abstract
Simple Summary The IMbrave150 trial led to the approval of atezolizumab and bevacizumab for the treatment of unresectable hepatocellular carcinoma (HCC). We performed a retrospective multicenter study including 115 patients with unresectable HCC treated with atezolizumab and bevacizumab, revealing that the combination of atezolizumab and bevacizumab is equally effective for patients meeting the IMbrave150 trial eligibility criteria and for patients not meeting these criteria, generally due to a history of systemic therapy, platelet counts < 75 x 10(9)/L, Child-Pugh B, and 2+ proteinuria. However, liver functional reserve should be carefully monitored in patients not meeting the IMbrave150 trial eligibility criteria. The IMbrave150 trial demonstrated the high efficacy and safety of atezolizumab and bevacizumab for unresectable hepatocellular carcinoma (HCC). In this multicenter study, the efficacy of this combination and its effect on liver functional reserve were evaluated in patients not meeting the eligibility criteria of IMbrave150. Of 115 patients with unresectable HCC treated with atezolizumab and bevacizumab between October 2020 and January 2022, 72 did not meet the eligibility criteria of IMbrave150, most frequently due to a history of systemic therapy (60/72), platelet counts < 75 x 10(9)/L (7/72), Child-Pugh B (9/72), and 2+ proteinuria (8/72). Atezolizumab and bevacizumab therapy was equally effective for patients who did or did not meet the eligibility criteria (PFS, 6.5 vs. 6.9 months, p = 0.765), consistent with subgroup analyses of histories of systemic therapy, platelet counts, Child-Pugh, and proteinuria. Baseline ALBI scores were worse in patients who did not meet the criteria than in those who did and significantly worsened after treatment initiation in patients not meeting the criteria (baseline vs. 12 weeks; 2.35 +/- 0.43 vs. -2.18 +/- 0.54; p = 0.007). Accordingly, atezolizumab plus bevacizumab was effective for patients not meeting the eligibility criteria of IMbrave150, although careful monitoring for changes in liver functional reserve is needed.
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- 2022
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29. Changes in the estimated renal function after hepatitis C virus eradication with direct‐acting antiviral agents: Impact of changes in skeletal muscle mass
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Mitsuteru Natsuizaka, Kazuharu Suzuki, Naoya Sakamoto, Megumi Kimura, Goki Suda, Ren Yamada, Takuya Sho, Yoshimasa Tokuchi, Masatsugu Ohara, Takashi Kitagataya, Masato Nakai, Kenichi Morikawa, Koji Ogawa, Naoki Kawagishi, Taku Shigesawa, and Osamu Maehara
- Subjects
medicine.medical_specialty ,Cirrhosis ,Hepatitis C virus ,Renal function ,Hepacivirus ,Kidney ,medicine.disease_cause ,Antiviral Agents ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Virology ,Internal medicine ,Humans ,Medicine ,030212 general & internal medicine ,Muscle, Skeletal ,Adverse effect ,Retrospective Studies ,Creatinine ,Hepatology ,biology ,business.industry ,Retrospective cohort study ,Hepatitis C, Chronic ,medicine.disease ,Skeletal muscle mass ,Infectious Diseases ,Cystatin C ,chemistry ,biology.protein ,030211 gastroenterology & hepatology ,business - Abstract
Hepatitis C virus (HCV) infection can cause renal dysfunction, expected to improve upon HCV eradication. However, adverse effects of HCV eradication using direct-acting antiviral agents (DAAs) on renal function have been recently reported. This retrospective study aimed to evaluate renal function with glomerular filtration rate (eGFR) estimated using creatinine (eGFRcre) and cystatin C (eGFRcys). Complete clinical information and preserved serum samples were collected from 207 patients with HCV infection treated with interferon-free DAA at baseline and SVR48 (SVR48). Patients who underwent paired computed tomography (CT) at baseline and ≥12 months after DAA were evaluated for changes in skeletal muscle mass using the psoas muscle mass index (PMI). eGFRcre significantly worsened at SVR48, while eGFRcys was similar at baseline and SVR48. At baseline, eGFRcre was significantly higher than eGFRcys; eGFRcre and eGFRcys were similar at SVR48. Multivariate analysis revealed that the presence of liver cirrhosis and low-albumin level, as well as cirrhosis and age, was significantly associated with the overestimation of renal function by eGFRcre at baseline and SVR48, respectively. In the 57 patients who underwent paired CT at baseline and ≥12 months after DAA, relative values of PMI significantly increased after DAA. After DAA, in patients with increased PMI (65% 37/57), eGFRcre significantly worsened but did not change in patients without increased PMI. eGFRcre significantly worsened after DAAs; however, this might not reflect accurate changes in renal function, partially because of changes in skeletal muscle mass. eGFRcys did not change after DAAs, and it is a potential alternative to eGFRcre.
- Published
- 2021
30. Tenofovir–disoproxil–fumarate modulates lipid metabolism via hepatic CD36/PPAR-alpha activation in hepatitis B virus infection
- Author
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Akihisa Nakamura, Mitsuteru Natsuizaka, Masatsugu Ohara, Takuya Sho, Naoya Sakamoto, Koji Yamamoto, Koji Ogawa, Naoki Kawagishi, Hideaki Miyoshi, Ren Yamada, Shunsuke Ohnishi, Takashi Kitagataya, Taku Shigesawa, Ken Furuya, Masato Nakai, Osamu Maehara, Akinobu Nakamura, Kenichi Morikawa, Masaru Baba, Yoshiya Yamamoto, Goki Suda, Kazuharu Suzuki, and Megumi Kimura
- Subjects
CD36 ,Peroxisome proliferator-activated receptor ,Pharmacology ,medicine.disease_cause ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Scavenger receptor ,chemistry.chemical_classification ,Hepatitis B virus ,biology ,Cholesterol ,business.industry ,Gastroenterology ,virus diseases ,Lipid metabolism ,Arteriosclerosis ,Entecavir ,medicine.disease ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,lipids (amino acids, peptides, and proteins) ,030211 gastroenterology & hepatology ,business ,medicine.drug - Abstract
Entecavir and tenofovir–disoproxil–fumarate are first-line nucleos(t)ide analogs (NA) for treatment of hepatitis B virus (HBV) infections; however, their long-term administration can impact extrahepatic organs. Herein, we sought to examine the effect of NA on lipid metabolism while also characterizing the associated mechanism. A retrospective study was performed on HBV patients administered entecavir or tenofovir–disoproxil–fumarate. Patient clinical information, as well as their preserved serum samples obtained at baseline and 6–12 months after treatment initiation, were analyzed. A 1:1 propensity score matching was applied to the assignment of tenofovir–disoproxil–fumarate or entecavir treatment. Changes in serum cholesterol, including oxidized-LDL, were analyzed. Subsequently, in vitro analysis elucidated the mechanism associated with the effect of NAs on lipid metabolism. Administration of tenofovir–disoproxil–fumarate, not entecavir, to chronic HBV patients, decreased serum cholesterol levels, including non-HDL and oxidized-LDL, which are strongly associated with arteriosclerosis. In vitro analysis revealed that tenofovir–disoproxil–fumarate reduced supernatant cholesterol, and upregulated the scavenger receptor, CD36, in hepatocytes. Meanwhile, silencing of hepatic CD36 increased supernatant cholesterol and negated the cholesterol-reducing effect of tenofovir–disoproxil–fumarate in HepG2-cells. Reporter, microarray, and RT-PCR analyses further revealed that tenofovir–disoproxil–fumarate treatment activates PPAR-α-mediated signaling, and upregulates PPAR-α target genes, including CPT1 and CD36. Alternatively, silencing of PPAR-α reversed the effects of tenofovir–disoproxil–fumarate on CD36. Tenofovir–disoproxil–fumarate modulates lipid metabolism by upregulating hepatic CD36 via PPAR-α activation. Since dyslipidemia could be associated with arteriosclerosis and hepatocarcinogenesis, these discoveries provide novel insights into anti-HBV therapies, as well as the associated extrahepatic effects of NA.
- Published
- 2020
31. Effects of nucleos(t)ide analogs on hepatitis B surface antigen reduction with interferon-lambda 3 induction in chronic hepatitis B patients
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Machiko Umemura, Koji Ogawa, Kenichi Morikawa, Akinori Kubo, Yoshimasa Tokuchi, Ren Yamada, Takashi Kitagataya, Taku Shigesawa, Tomoe Shimazaki, Megumi Kimura, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Naoki Kawagishi, Takaaki Izumi, Masato Nakai, Takuya Sho, Goki Suda, Mitsuteru Natsuizaka, Kota Ono, Kazumoto Murata, Masaya Sugiyama, Masashi Mizokami, and Naoya Sakamoto
- Subjects
Infectious Diseases ,Hepatology - Abstract
Benefits of nucleos(t)ide analogs (NAs) on hepatitis B surface antigen (HBsAg) reduction and interferon-lambda3 (IFN-λ3) induction are still not known. This study aimed to investigate the effects of NAs on HBsAg reduction and association with serum IFN-λ3 levels in chronic hepatitis B (CHB) patients.A total of 91 patients [51 treated with nucleoside analog entecavir hydrate (ETV) and 40 treated with nucleotide analog adefovir dipivoxil (ADV) or tenofovir disoproxil fumarate (TDF)] with clinically evident CHB (chronic hepatitis, 57; liver cirrhosis, 34) were enrolled in this study. Serum IFN-λ3 levels among patients receiving ETV and ADV/TDF were measured before the initiation of therapy and 1, 3, and 5 years post-therapy.The change (mean ± standard deviation) in serum HBsAg levels from baseline to year five was -0.38 ± 0.46 and -0.84 ± 0.64 logNucleotide analog (ADV/TDF) treatment reduced HBsAg levels greater compared with nucleoside analog (ETV) in parallel with IFN-λ3 induction.
- Published
- 2022
32. Successful Resection of a Gastric Tumor With Severe Fibrosis Using Endoscopic Submucosal Tunnel Dissection and a Picking Technique With a Clutch Cutter
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Satoshi Abiko, Katsuma Nakajima, Koji Hirata, Kazuharu Suzuki, Kenji Kinoshita, Kazuteru Hatanaka, Yoshiya Yamamoto, and Hirohito Naruse
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General Medicine - Published
- 2022
33. Overestimated renal function in patients with liver cirrhosis predicts poor prognosis
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Sonoe Yoshida, Goki Suda, Masatsugu Ohara, Megumi Kimura, Zijian Yang, Osamu Maehara, Qingjie Fu, Shunichi Hosoda, Kubo Akinori, Yoshimasa Tokuchi, Ren Yamada, Takashi Kitagataya, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Shunsuke Ohnishi, and Naoya Sakamoto
- Subjects
Infectious Diseases ,Hepatology - Abstract
A high prevalence of overestimated renal function in patients with liver cirrhosis (LC) has been reported; nonetheless, its impact on prognosis remains unclear. We aimed to evaluate the impact of overestimated renal function on prognosis in patients with LC.An overestimated renal function was defined as a20% increase in the creatinine-based estimated glomerular filtration rate (eGFR), compared with cystatin C-based eGFR. LC patients with conserved serum, who were evaluated for muscle atrophy and had proper clinical information were included, and their prognostic factors were analyzed.A total of 215 consecutive patients with LC were included. The prevalence of overestimated renal function was 29.8% (64/215). Kaplan-Meier survival analysis revealed that patients with overestimated renal function had a poorer prognosis than those without overestimated renal function (hazard ratio [HR]: 2.217 95% confidence interval [CI]: 1.290-3.810; p = 0.001). Subgroup analysis showed that overestimated renal function was a significant prognostic factor, irrespective of sex and the presence of hepatocellular carcinoma (HCC). Multivariate Cox regression analyses revealed that overestimated renal function was a significant and independent factor predictive of poor prognosis in the entire cohort (HR: 2.050; 95% CI: 1.041-4.037; p = 0.038) and in subgroups classified by Child-Pugh class A (HR: 2.131; 95% CI: 1.019-4.458; p = 0.044), Model for End-Stage Liver Disease score ≤9 (HR: 2.303; 95% CI: 1.038-5.109; p = 0.04), and presence of HCC (HR: 2.290; 95% CI: 1.128-4.651; p = 0.022).Overestimated renal function is a significant and independent prognostic factor in patients with LC.
- Published
- 2022
34. Hepatocellular Carcinoma Rupture after Introducing Lenvatinib: An Autopsy Case Report.
- Author
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Risako Kohya, Ryo Sugiura, Yoshiya Yamamoto, Hirohito Naruse, Kazuteru Hatanaka, Kenji Kinoshita, Satoshi Abiko, Shuichi Miyamoto, Kazuharu Suzuki, Hanae Kushibiki, Satoru Munakata, and Norihiko Shimoyama
- Published
- 2023
- Full Text
- View/download PDF
35. Percutaneous Retrieval of an Inferior Vena Cava Filter Penetrating Into the Duodenum
- Author
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Jiro Koya, Yutaro Yasui, Kazuya Sugitatsu, Kazuharu Suzuki, Shuichi Miyamoto, Yusuke Tokuda, Hiroyuki Gibo, Yasuhiro Makita, Morio Shoda, and Shota Saito
- Subjects
medicine.medical_specialty ,Vena Cava Filters ,Percutaneous ,Duodenum ,business.industry ,Ivc filter ,Inferior vena cava filter ,Vena Cava, Inferior ,Treatment Outcome ,medicine.anatomical_structure ,medicine ,Humans ,Radiology ,Cardiology and Cardiovascular Medicine ,business ,Device Removal ,Retrospective Studies - Published
- 2021
36. Baseline angiopoietin-2 and FGF19 levels predict treatment response in patients receiving multikinase inhibitors for hepatocellular carcinoma
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Akihisa Nakamura, Naoya Sakamoto, Takuya Sho, Osamu Maehara, Kenichi Morikawa, Masatsugu Ohara, Machiko Umemura, Kazuharu Suzuki, Goki Suda, Koji Ogawa, Naoki Kawagishi, Mitsuteru Natsuizaka, Takashi Kitagataya, Megumi Kimura, Masato Nakai, Taku Shigesawa, Tomoe Shimazaki, and Ren Yamada
- Subjects
Oncology ,Sorafenib ,medicine.medical_specialty ,Treatment response ,RC799-869 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Stable Disease ,Internal medicine ,medicine ,fibroblast growth factor 19 ,Hepatology ,business.industry ,Angiopoietin 2 ,Gastroenterology ,FGF19 ,Original Articles ,hepatocellular carcinoma ,Diseases of the digestive system. Gastroenterology ,medicine.disease ,digestive system diseases ,angiopoietin‐2 ,Vascular endothelial growth factor ,chemistry ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,treatment outcome ,Original Article ,030211 gastroenterology & hepatology ,angiopoietin-2 ,sorafenib ,Lenvatinib ,business ,medicine.drug - Abstract
Background Sorafenib and lenvatinib are first‐line systemic therapies for unresectable hepatocellular carcinoma (HCC). However, the criteria for their selection remain unclear. Methods We identified patients with unresectable HCC who were treated with sorafenib or lenvatinib between August 2009 and January 2019 at the Hokkaido University Hospital. Patients who continued treatment for >2 months, underwent evaluation by computed tomography every 2–3 months, and had complete clinical data were included. Responders were patients with objective response (OR) for lenvatinib and patients with stable disease (SD) exceeding 6 months (long‐SD) or OR for sorafenib. The predictive factors for treatment response, including fibroblast growth factor (FGF)19 and 21, angiopoietin 2 (ANG2), hepatocyte growth factor, and vascular endothelial growth factor, were evaluated. Results Overall, 27 and 29 patients treated with lenvatinib and sorafenib, respectively, were included. The responders for lenvatinib and sorafenib were 63% (17/27) and 38% (11/29), respectively. No significant predictive factors for treatment response were identified in patients treated with sorafenib. However, baseline serum FGF19 and ANG2 levels were significantly associated with treatment response to lenvatinib. All (9/9) patients with low baseline ANG2 and FGF19 levels who received lenvatinib achieved OR. Conversely, the OR was low (13%; 1/9) in patients with high baseline ANG2 and FGF19 levels. Responder rate was 40% (2/5) in patients with high baseline ANG2 and FGF19 levels who received sorafenib. Conclusion This study is, to our knowledge, the first to demonstrate that baseline ANG2 and FGF19 levels may aid in selecting optimal systemic therapy for patients with unresectable HCC., The combination of baseline serum ANG2 and FGF19 levels may predict treatment response to lenvatinib in patients with unresectable HCC. An OR was achieved in all patients with low baseline levels of ANG2 and FGF19 treated with lenvatinib (100%, 9/9). Conversely, those with high baseline levels of these markers demonstrated a low OR rate (13%; 1/9). However, in patients with high baseline ANG2 and FGF19 levels, the response to sorafenib was not low (40% 2/5). These findings show, for the first time, that baseline biomarker levels may determine suitability for systemic therapy in patients with unresectable HCC.
- Published
- 2020
37. Durable response without recurrence to Tolvaptan improves long-term survival
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Kazuharu Suzuki, Takuya Sho, Masatsugu Ohara, Goki Suda, Koji Ogawa, Naoki Kawagishi, Akihisa Nakamura, Takashi Kitagataya, Kenichi Morikawa, Ren Yamada, Yoshimasa Tokuchi, Akinori Kubo, Machiko Umemura, Masato Nakai, Taku Shigesawa, and Naoya Sakamoto
- Subjects
Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Time Factors ,Cirrhosis ,Adolescent ,Pleural effusion ,Urinary system ,Tolvaptan ,Renal function ,Gastroenterology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Internal medicine ,medicine ,Humans ,Aged ,Retrospective Studies ,Aged, 80 and over ,biology ,business.industry ,C-reactive protein ,Acute kidney injury ,Middle Aged ,Hepatology ,Prognosis ,medicine.disease ,Treatment Outcome ,030220 oncology & carcinogenesis ,biology.protein ,Female ,030211 gastroenterology & hepatology ,business ,Antidiuretic Hormone Receptor Antagonists ,Follow-Up Studies ,medicine.drug - Abstract
Decompensated liver cirrhosis patients with refractory ascites or pleural effusion have a poor prognosis. Tolvaptan has been used for treating water retention associated with cirrhosis. However, despite the short-term response, water retention recurrence is still observed in some cases. This study aimed to clarify the water retention recurrence rate and the relationship between long-term response without recurrence and prognosis. Altogether, 100 patients with decompensated cirrhosis treated with tolvaptan were retrospectively analyzed. Recurrence was evaluated according to the criteria of the EASL clinical practice guideline. The recurrence rate and prognosis of non-responders, patients with recurrence, and long-term responders were analyzed. The baseline factors related to short-term response, recurrence, and long-term response were also evaluated. Approximately 31.0% of the short-term responders had recurrence. Although there was no significant difference in the prognosis by short-term response (p = 0.07), the long-term responders had a significantly better prognosis than those with recurrence and non-responders (p
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- 2020
38. Computed tomography, not bioelectrical impedance analysis, is the proper method for evaluating changes in skeletal muscle mass in liver disease
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Tomoe Shimazaki, Osamu Maehara, Naoya Sakamoto, Akihisa Nakamura, Kenichi Morikawa, Masatsugu Ohara, Taku Shigesawa, Kazuharu Suzuki, Koji Ogawa, Naoki Kawagishi, Megumi Kimura, Takuya Sho, Mitsuteru Natsuizaka, Masato Nakai, and Goki Suda
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lcsh:Internal medicine ,medicine.diagnostic_test ,business.industry ,Secondary sarcopenia ,Computed tomography ,medicine.disease ,Skeletal muscle mass ,Psoas muscle mass index ,Liver disease ,BIA ,medicine ,lcsh:RC31-1245 ,Nuclear medicine ,business ,Bioelectrical impedance analysis - Abstract
Background Sarcopenia is associated with poor prognosis in patients with chronic liver disease (CLD). As rapid skeletal muscle wasting predicts worse prognosis and a novel therapy for sarcopenia needs to be evaluated for validation, accurate evaluation methods for relative changes in muscle mass are crucial. Methods We screened CLD patients who had skeletal muscle mass evaluation between June 2015 and December 2017. Patients were included if they had adequate information, were followed for >6 months, and had skeletal muscle mass evaluation by both bioelectrical impedance analysis (BIA) and computed tomography (CT) imaging at baseline and the second evaluation point. We compared BIA and CT imaging in terms of their ability to quantify skeletal muscle mass and identify relative changes in muscle mass in CLD patients. Results Of the screened 447 CLD patients, 110 were included in this study, and 71 (64.5%) were men. The median age was 68 (range 21 to 90) years. In total, 83 (75.5%) and 32 (29.1%) patients had liver cirrhosis and hepatocellular carcinoma, respectively. Of them, 50 (45.5%) patients were liver cirrhosis patients without hepatocellular carcinoma through the observation period. Skeletal muscle mass index (SMI) by BIA, psoas muscle mass index (PMI), and SMI based on CT imaging were significantly correlated at baseline [SMI by simple CT method and SMI by BIA (r = 0.61, P
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- 2020
39. Lenvatinib suppresses cancer stem-like cells in HCC by inhibiting FGFR1–3 signaling, but not FGFR4 signaling
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Takashi Kitagataya, Ren Yamada, Koji Yamamoto, Goki Suda, Masatsugu Ohara, Akihisa Nakamura, Machiko Umemura, Masaya Sugiyama, Kenichi Morikawa, Kazuharu Suzuki, Masato Nakai, Koji Ogawa, Naoki Kawagishi, Osamu Maehara, Naoya Sakamoto, Mitsuteru Natsuizaka, Masashi Mizokami, Takuya Sho, Hiroshi Takeda, Shunsuke Ohnishi, Megumi Kimura, Tomoe Shimazaki, and Taku Shigesawa
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0301 basic medicine ,Cancer Research ,Cell ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Molecular Targeted Therapy ,biology ,Liver Neoplasms ,General Medicine ,Sorafenib ,medicine.anatomical_structure ,Fibroblast growth factor receptor ,030220 oncology & carcinogenesis ,Neoplastic Stem Cells ,Quinolines ,Female ,Fibroblast Growth Factor 2 ,Fluorouracil ,Lenvatinib ,Signal Transduction ,medicine.drug ,Carcinoma, Hepatocellular ,03 medical and health sciences ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Receptor, Fibroblast Growth Factor, Type 3 ,Receptor, Fibroblast Growth Factor, Type 4 ,Receptor, Fibroblast Growth Factor, Type 1 ,Receptor, Fibroblast Growth Factor, Type 2 ,Protein Kinase Inhibitors ,neoplasms ,business.industry ,Phenylurea Compounds ,Fibroblast growth factor receptor 1 ,CD44 ,Cancer ,Fibroblast growth factor receptor 4 ,medicine.disease ,Xenograft Model Antitumor Assays ,digestive system diseases ,Fibroblast Growth Factors ,030104 developmental biology ,chemistry ,Cancer research ,biology.protein ,business - Abstract
In hepatocellular carcinoma (HCC), a subset of cells defined by high CD44 and CD133 expression has been reported to possess cancer stem-like cell (CSC) characteristics and to be associated with a poor prognosis. Since the approval of the multikinase inhibitor, lenvatinib, for patients with unresectable HCC, two such inhibitors (sorafenib and lenvatinib) have been employed as first-line systemic chemotherapeutics for these patients. Based on differences in the kinase-affinity profiles between these two drugs, evidence has suggested that both exert different effects on HCC, although these differences are not fully characterized. In this study, using in vitro and a preclinical in vivo xenograft mouse model, we showed that lenvatinib alone (not sorafenib or the cytotoxic agent, 5-fluorouracil) diminished CD44High/CD133High CSCs in HCC. Furthermore, western blotting and reverse transcriptase-polymerase chain reaction analysis revealed that the expression of fibroblast growth factor receptor (FGFR)-1–4 differed between CD44High/CD133High CSCs and control cells. Analysis of the effects of selective FGFR inhibitors and FGFR small interfering RNAs on CSCs in HCC revealed that lenvatinib diminished CSCs in HCC by inhibiting FGFR1–3 signaling, however, FGFR4 signaling was not impacted. Finally, we showed that FGF2 and FGF19 were involved in maintaining CD44High/CD133High CSCs in HCC, potentially, via FGFR1–3. The findings provide novel mechanistic insights into the effects of lenvatinib on CSCs in HCC and provide clues for developing effective targeted therapies against CSCs in HCC.
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- 2020
40. Analysis of the optimal psoas muscle mass index cut‐off values, as measured by computed tomography, for the diagnosis of loss of skeletal muscle mass in Japanese people
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Takuya Sho, Kazuharu Suzuki, Kenichi Morikawa, Masatsugu Ohara, Ryo Takagi, Minoru Uebayashi, Masato Nakai, Isao Yokota, Koji Ogawa, Naoki Kawagishi, Tsuyoshi Shimamura, Goki Suda, Tomoe Shimazaki, Mitsuteru Natsuizaka, Megumi Kimura, Osamu Maehara, Tomoe Kobayashi, Taku Shigesawa, Akihisa Nakamura, and Naoya Sakamoto
- Subjects
medicine.medical_specialty ,Cirrhosis ,Hepatology ,medicine.diagnostic_test ,business.industry ,Urology ,Computed tomography ,Chronic liver disease ,medicine.disease ,Muscle mass ,Skeletal muscle mass ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Infectious Diseases ,030220 oncology & carcinogenesis ,Sarcopenia ,medicine ,030211 gastroenterology & hepatology ,business ,Bioelectrical impedance analysis - Abstract
This study aimed to determine the optimal psoas muscle mass index (PMI) cut-off values for diagnosis of skeletal muscle mass loss. Methods We evaluated PMI in two groups of normal controls: a medical check-up group and a liver donation candidate group. We analyzed two novel PMI cut-off values, one based on the mean - two standard deviations (2SD) and one based on the lower 5%. Skeletal muscle mass index (SMI) evaluations using computed tomography (sliceOmatic; TomoVision) and bioelectrical impedance analysis and PMI evaluation were undertaken simultaneously. We analyzed the correlation between our PMI cut-off values and the Japan Society of Hepatology-defined SMI cut-off values. The prevalence of skeletal muscle mass loss in patients with liver disease was assessed using the novel PMI cut-off values. Results In 504 normal controls aged ≤50 years, the PMI cut-off values based on mean -2SD and the lower 5% were set at 3.30 cm2 /m2 for men and 1.69 cm2 /m2 for women and 3.74 cm2 /m2 for men and 2.29 cm2 /m2 for women, respectively. The PMI cut-off values based on the lower 5% alone showed that skeletal muscle mass loss increased with age. Furthermore, they correlated well with Japan Society of Hepatology-defined SMI (sliceOmatic) cut-off values and showed a significantly higher prevalence of skeletal muscle mass loss in patients with liver cirrhosis than those without liver cirrhosis. Conclusions We propose the following PMI cut-off values: 3.74 cm2 /m2 for male individuals and 2.29 cm2 /m2 for female individuals. These cut-off values can facilitate accurate diagnosis and management of sarcopenia in patients with chronic liver disease.
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- 2020
41. Prevalence, clinical course, and predictive factors of immune checkpoint inhibitor monotherapy‐associated hepatitis in Japan
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Satoshi Takeuchi, Osamu Maehara, Akihiro Homma, Shunsuke Ohnishi, Naoya Sakamoto, Mitsuteru Natsuizaka, Akihisa Nakamura, Ren Yamada, Takashi Kitagataya, Megumi Kimura, Yoshito Komatsu, Koji Yamamoto, Kazunori Nagashima, Takehiko Katsurada, Goki Suda, Takashige Abe, Jun Sakakibara-Konishi, Masatsugu Ohara, Takanori Teshima, Machiko Umemura, Hiroo Hata, Masato Nakai, Kenichi Morikawa, Koji Ogawa, Naoki Kawagishi, Takuya Sho, Kazuharu Suzuki, and Taku Shigesawa
- Subjects
Adult ,Male ,medicine.medical_specialty ,immune checkpoint inhibitor ,Ipilimumab ,Pembrolizumab ,Antibodies, Monoclonal, Humanized ,Severity of Illness Index ,Gastroenterology ,Antineoplastic Agents, Immunological ,Japan ,irAE ,Internal medicine ,Prevalence ,medicine ,Humans ,hepatitis ,Risk factor ,Adverse effect ,Aged ,Retrospective Studies ,Aged, 80 and over ,Hepatitis ,Hepatology ,business.industry ,Incidence (epidemiology) ,Retrospective cohort study ,Middle Aged ,medicine.disease ,adverse events ,immune system ,Nivolumab ,female ,risk factor ,Chemical and Drug Induced Liver Injury ,business ,Forecasting ,medicine.drug - Abstract
Background and Aim Immune checkpoint inhibitors (ICI) have revolutionized anti-malignancy therapy and thus have been increasingly used. Although ICI may cause immune-related adverse events (irAE) in various organs, including the liver, the prevalence and predictive factors of irAE have not been clarified. Methods In this retrospective study, consecutive patients who had malignancies and were treated with ICI without other chemotherapeutic agents at Hokkaido University Hospital between 2014 and 2019 were screened. Patients were excluded if they were Of the 233 patients screened, 202 patients met the inclusion criteria and were included in the analysis. The patients were aged 25-92 years, and 60.9% were male. The patients received nivolumab (n = 137), pembrolizumab (n = 45), ipilimumab (n = 17), atezolizumab (n = 2), and avelumab (n = 1). The prevalence of any grade and grade >= 3 irAE hepatitis was 8.4% (17/202) and 4.0% (8/202), respectively. irAE hepatitis occurred at a median duration of 42 days in any grade and 36 days in grade >= 3 after ICI initiation. The clinical course of grade >= 3 irAE hepatitis was generally favorable; however, 50% required corticosteroid treatment and two patients required additional mycophenolate mofetil. Female sex and history of ICI treatment were significantly associated with the incidence of grade >= 3 irAE hepatitis. Conclusions Grade >= 3 irAE hepatitis was observed in 4.0% of the patients who were treated with ICI. Female sex and history of ICI treatment were significantly associated with the incidence of grade >= 3 irAE hepatitis.
- Published
- 2020
42. High serum angiopoietin‐2 level predicts non‐regression of liver stiffness measurement‐based liver fibrosis stage after direct‐acting antiviral therapy for hepatitis C
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Masato Nakai, Akihisa Nakamura, Tomoe Shimazaki, Machiko Umemura, Mutsumi Nishida, Masatsugu Ohara, Megumi Kimura, Kenichi Morikawa, Ren Yamada, Kazuharu Suzuki, Naoya Sakamoto, Mitsuteru Natsuizaka, Koji Ogawa, Naoki Kawagishi, Taku Shigesawa, Takashi Kitagataya, Goki Suda, Takuya Sho, Osamu Maehara, and Yusuke Kudo
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Hepatitis C virus ,Spleen ,Retrospective cohort study ,Inflammation ,Hepatitis C ,medicine.disease ,medicine.disease_cause ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Infectious Diseases ,medicine.anatomical_structure ,Interferon ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,030211 gastroenterology & hepatology ,medicine.symptom ,Stage (cooking) ,business ,Transient elastography ,medicine.drug - Abstract
Aim Factors associated with improvement of liver fibrosis after successful hepatitis C virus (HCV) eradication by interferon (IFN)-free direct-acting antiviral agents (DAAs) have been not clarified well. Angiopoietin-2 (Ang2) is reported to be associated with vascular leak and inflammation observed in patients with advanced liver fibrosis. Methods In this retrospective study, patients treated with IFN-free DAAs who underwent transient elastography before and at 24-weeks post-treatment and achieved sustained viral response were enrolled. Baseline serum Ang2 was measured, and its relationship with other clinical factors was analyzed. Liver fibrosis stage was defined based on liver stiffness according to a previous report. Predictive factors for regression of liver fibrosis stage after DAA therapy were evaluated. Results Overall, 116 patients were analyzed. Baseline serum Ang2 levels were significantly associated with liver stiffness, spleen index, and liver stiffness-based liver fibrosis stage. Moreover, 75% of patients experienced regression of liver fibrosis stage after DAA therapy. Multivariate analysis revealed that advanced liver fibrosis stage and Ang2 levels were significantly associated with regression of liver fibrosis stage after DAA therapy. In patients with advanced liver fibrosis (F3/4), baseline Ang2 level alone could predict regression of liver fibrosis stage. A baseline Ang2 cut-off value (354 pg/ML) could predict regression of liver fibrosis stage after DAA therapy with high accuracy (sensitivity 0.882, specificity 0.733). Conclusions Evaluation of serum Ang2 levels before DAA therapy is important. Our results provide a novel mechanistic insight into non-regression of liver stiffness after DAA therapy. Long-term and larger studies are required.
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- 2020
43. The potential of soluble CD14 in discriminating nonalcoholic steatohepatitis from nonalcoholic fatty liver disease
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Akihisa Nakamura, Koji Yamamoto, Rei Takeda, Ren Yamada, Akinori Kubo, Kenichi Morikawa, Sayaka Ando, Tomoe Shimazaki, Takaaki Izumi, Machiko Umemura, Takashi Kitagataya, Taku Shigesawa, Kazuharu Suzuki, Megumi Kimura, Masato Nakai, Takuya Sho, Goki Suda, Mitsuteru Natsuizaka, Koji Ogawa, Shunsuke Ohnishi, Toshiro Sugiyama, Hiroshi Takeda, and Naoya Sakamoto
- Subjects
Infectious Diseases ,Hepatology - Abstract
Although various noninvasive markers and prediction formulas for nonalcoholic steatohepatitis (NASH) have been reported, they are of value only in the diagnosis of the advanced fibrosis stage of NASH. In this study, we evaluated soluble CD14 (sCD14) as a diagnostic marker for discriminating NASH from nonalcoholic fatty liver disease (NAFLD) using an animal model and clinical specimens.Serum sCD14 levels were measured in samples derived from mice with diet-induced NASH and patients using an enzyme-linked immunosorbent assay. Our cohort enrolled 126 patients with liver needle biopsy-proven NAFLD.The intestinal defense mechanism in NASH model mice was altered as a consequence of the unique gut environment. Elevated serum levels of sCD14 were observed in mice with diet-induced NASH, and the condition of the liver was exacerbated as a result of exposure to gut-derived endotoxin. We confirmed that the serum sCD14 levels in NAFL patients significantly differed from those in NASH patients. The area under the curve for distinguishing between NAFL and NASH was 0.891. Moreover, we found that serum sCD14 levels were weakly correlated with the inflammation grade based on the NAFLD activity score (NAS), the grade of fibrosis according to the Brunt fibrosis classification, and a positive correlation with the grade of ballooning based on NAS in patients with NAFLD.sCD14 could be a useful pathophysiological marker and diagnostic adjunct distinguishing NASH from NAFLD. The use of sCD14 may allow the screening and identification of high-risk groups for NASH development and support early therapeutic interventions.
- Published
- 2022
44. Changes in Serum Growth Factors during Resistance to Atezolizumab Plus Bevacizumab Treatment in Patients with Unresectable Hepatocellular Carcinoma
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Zijian Yang, Goki Suda, Osamu Maehara, Masatsugu Ohara, Tomoka Yoda, Takashi Sasaki, Risako Kohya, Sonoe Yoshida, Shunichi Hosoda, Yoshimasa Tokuchi, Takashi Kitagataya, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Koji Ogawa, Shunsuke Ohnishi, and Naoya Sakamoto
- Subjects
resistance ,atezolizumab ,Cancer Research ,Oncology ,mechanism ,immune checkpoint inhibitor ,angiopoietin-2 ,bevacizumab ,hepatocellular carcinoma ,progressive disease ,VEGF-D - Abstract
Simple Summary The possible mechanisms of resistance to atezolizumab/bevacizumab for unresectable HCC and the subsequent response to these therapies remain underexplored. The sequential changes in serum growth factors, including VEGF-A, VEGF-C, VEGF-D, ANG-2, FGF-19, HGF, and EGF during atezolizumab/bevacizumab for unresectable HCC were evaluated in 46 patients. Of 32 patients with disease control, 28 experienced PD after CR, PR, or SD with atezolizumab/bevacizumab. Growth factor changes between the baseline and best overall response points (BOR) for patients with disease control showed that FGF-19 significantly increased and ANG2 significantly decreased at the BOR. Growth factor changes between the BOR and the PD point in 28 patients who experienced PD after disease control showed that VEGF-D and ANG2 significantly increased at the PD point compared with that at the BOR. Summarily, increased serum VEGF-D and ANG-2 levels might contribute to developing resistance to atezolizumab/bevacizumab for unresectable HCC and might be target molecules in subsequent salvage therapies. The possible mechanisms of resistance to atezolizumab/bevacizumab for unresectable HCC, and the subsequent response to these therapies, remain underexplored. The sequential changes in serum growth factors, including VEGF-A, VEGF-C, VEGF-D, ANG-2, FGF-19, HGF, and EGF during atezolizumab/bevacizumab for unresectable HCC were evaluated in 46 patients. Patients who experienced PD after CR, PR, or SD to atezolizumab/bevacizumab were evaluated. A total of 4, 9, 19, and 14 patients showed CR, PR, SD, and PD, respectively. Of 32 patients with disease control, 28 experienced PD after CR, PR, or SD with atezolizumab/bevacizumab. Baseline growth factor levels were similar between patients with or without disease control and those with or without an objective response. Growth factor changes between the baseline and the best overall response points (BOR) for patients with disease control showed that FGF-19 significantly increased and ANG2 significantly decreased at the BOR. Growth factor changes between the BOR and the PD point in 28 patients who experienced PD after disease control showed that VEGF-D and ANG2 significantly increased at the PD point compared with that at the BOR. Summarily, increased serum VEGF-D and ANG-2 levels might contribute to developing resistance to atezolizumab/bevacizumab for unresectable HCC and might be target molecules in subsequent salvage therapies.
- Published
- 2023
45. Evaluation of clinical utility of PIVKA-II using a chemiluminescent immunoassay
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Koji Ogawa, Masato Nakai, Takuya Sho, Kenichi Morikawa, Kazuharu Suzuki, Naoya Sakamoto, and Goki Suda
- Subjects
Chromatography ,Hepatology ,Chemiluminescent immunoassay ,Chemistry - Published
- 2019
46. FEASIBILITY OF A NEW LIGATION USING THE DOUBLE-LOOP CLIPS TECHNIQUE WITHOUT AN ADHESIVE AGENT FOR ULCERATION AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION OF THE COLON
- Author
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Satoshi Abiko, Soichiro Oda, Akimitsu Meno, Akane Shido, Sonoe Yoshida, Ayumu Yoshikawa, Kazuaki Harada, Naoki Kawagishi, Itsuki Sano, Hisashi Oda, Katsuma Nakajima, Koji Hirata, Kazuharu Suzuki, Kazuteru Hatanaka, Yoshiya Yamamoto, Hirohito Naruse, and Takuto Miyagishima
- Subjects
Gastroenterology ,Radiology, Nuclear Medicine and imaging - Published
- 2022
47. Possible correlation between increased serum free carnitine levels and increased skeletal muscle mass following HCV eradication by direct acting antivirals
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Takashi Kitagataya, Yoshimasa Tokuchi, Masato Nakai, Kenichi Morikawa, Shunsuke Ohnishi, Masatsugu Ohara, Kazuharu Suzuki, Goki Suda, Sonoe Yoshida, Mitsuteru Natsuizaka, Shunichi Hosoda, Megumi Kimura, Ren Yamada, Takuya Sho, Zijian Yang, Qingjie Fu, Osamu Maehara, Akinori Kubo, Koji Ogawa, Naoki Kawagishi, and Naoya Sakamoto
- Subjects
Adult ,Male ,medicine.medical_specialty ,Sustained Virologic Response ,Science ,Hepatitis C virus ,Chronic liver disease ,medicine.disease_cause ,DIRECT ACTING ANTIVIRALS ,Antiviral Agents ,Gastroenterology ,Article ,Serum free ,Carnitine ,Internal medicine ,medicine ,Humans ,Insulin-Like Growth Factor I ,Vitamin D ,Aged ,Psoas Muscles ,Aged, 80 and over ,Multidisciplinary ,Hepatology ,business.industry ,Skeletal muscle ,Organ Size ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Skeletal muscle mass ,Zinc ,medicine.anatomical_structure ,Medicine ,Female ,business ,Amino Acids, Branched-Chain ,medicine.drug - Abstract
We aimed to evaluate factors associated with changes in skeletal muscle mass in hepatitis C virus (HCV)-infected patients after treatment with direct-acting antivirals (DAAs). Consecutive HCV-infected patients after treatment with DAA were recruited into the study. Patients who achieved sustained virological response (SVR); and had complete clinical information, preserved serum samples at baseline and SVR48, and skeletal muscle mass evaluations based on the psoas muscle mass index (PMI) on computed tomography at baseline and ≥ 12 months were included. Altogether, 70.7% of patients (41/58) showed increased PMI after DAA therapy, and mean relative PMI was significantly higher after DAA therapy than at baseline. There were no significant associations between baseline clinical factors routinely examined in clinical practice and increased PMI. Among factors reported to be associated with skeletal muscle loss in patients with chronic liver disease, serum zinc levels and total and free carnitine levels increased significantly after DAA therapy and only changes in serum free carnitine levels were significantly associated with an increased PMI (r = 0305, P = 0.020). In conclusion, increased skeletal muscle mass after successful HCV eradication by DAAs was significantly associated with increased serum-free carnitine levels. l-carnitine supplementation may be beneficial in patients with low skeletal muscle mass after DAA.
- Published
- 2021
48. Early response and safety of atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma in patients who do not meet IMbrave150 eligibility criteria
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Takuya Sho, Ken Furuya, Masaru Baba, Masatsugu Ohara, Kazuharu Suzuki, Osamu Maehara, Taku Shigesawa, Jun Ito, Shunsuke Ohnishi, Yoshimasa Tokuchi, Katsumi Terashita, Koji Ogawa, Naoki Kawagishi, Takaaki Izumi, Takashi Kitagataya, Megumi Kimura, Akinori Kubo, Masato Nakai, Takashi Meguro, Kenichi Morikawa, Akihisa Nakamura, Takuto Miyagishima, Mitsuteru Natsuizaka, Naoya Sakamoto, Goki Suda, Yoshiya Yamamoto, and Ren Yamada
- Subjects
medicine.medical_specialty ,Hepatology ,Bevacizumab ,Combination therapy ,business.industry ,medicine.disease ,Clinical trial ,Infectious Diseases ,Atezolizumab ,Response Evaluation Criteria in Solid Tumors ,Internal medicine ,Hepatocellular carcinoma ,medicine ,business ,Adverse effect ,Progressive disease ,medicine.drug - Abstract
AIM A clinical trial (IMbrave150) indicated the efficacy and safety of atezolizumab plus bevacizumab for patients with unresectable hepatocellular carcinoma (HCC). In this study, we evaluated this therapeutic combination in a real-world setting, with a focus on patients who did not meet the IMbrave150 eligibility criteria. METHODS In this multicenter study, patients with unresectable HCC treated with atezolizumab plus bevacizumab between October 2020 and May 2021 were screened. In patients who did not meet IMbrave150 eligibility criteria, treatment responses and safety at 6 and 12 weeks were evaluated. RESULTS Atezolizumab plus bevacizumab was initiated in 64 patients, including 46 patients (71.9%) who did not meet IMbrave150 eligibility criteria. Most of these patients had a history of systemic therapy (44/46). The objective response rate and disease control rate observed using Response Evaluation Criteria in Solid Tumors 1.1 were 5.2% and 82.8% at 6 weeks and 10.0% and 84.0% at 12 weeks, respectively; these rates were similar between patients who met and did not meet the IMbrave150 criteria. Ten patients experienced progressive disease (PD) at 6 weeks. Portal vein tumor thrombosis was significantly associated with PD (p = 0.039); none of the 15 patients with hepatitis B virus-related HCC experienced PD (p = 0.050). The most common adverse events of grade 3 or higher were aspartate aminotransferase elevation (n = 8, 13.8%) and the safety profile was similar between patients who met and did not meet the IMbrave150 criteria. CONCLUSION Most patients treated with atezolizumab plus bevacizumab did not meet the IMbrave150 criteria; however, the combination therapy showed good safety and efficacy at the early treatment phase.
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- 2021
49. Frequency and Characteristics of Overestimated Renal Function in Japanese Patients with Chronic Liver Disease and Its Relation to Sarcopenia
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Qingjie Fu, Takuya Sho, Mitsuteru Natsuizaka, Osamu Maehara, Takashi Kitagataya, Kubo Akinori, Kenichi Morikawa, Yoshimasa Tokuchi, Shunsuke Ohnishi, Masatsugu Ohara, Koji Ogawa, Naoki Kawagishi, Sonoe Yoshida, Masato Nakai, Kazuharu Suzuki, Ren Yamada, Zijian Yang, Shunichi Hosoda, Megumi Kimura, Goki Suda, and Naoya Sakamoto
- Subjects
Male ,Sarcopenia ,Cirrhosis ,urologic and male genital diseases ,Chronic liver disease ,Kidney ,Liver disease ,chemistry.chemical_compound ,0302 clinical medicine ,Japan ,Medicine ,TX341-641 ,Psoas Muscles ,Aged, 80 and over ,Nutrition and Dietetics ,Liver Diseases ,Middle Aged ,Muscle atrophy ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Creatinine ,Body Composition ,030211 gastroenterology & hepatology ,Female ,Kidney Diseases ,medicine.symptom ,liver disease ,Glomerular Filtration Rate ,Adult ,medicine.medical_specialty ,Urology ,Renal function ,Article ,03 medical and health sciences ,Young Adult ,Predictive Value of Tests ,Humans ,skeletal muscle ,Cystatin C ,Aged ,Retrospective Studies ,Nutrition. Foods and food supply ,business.industry ,renal function ,Skeletal muscle ,Reproducibility of Results ,medicine.disease ,chemistry ,Chronic Disease ,business ,Tomography, X-Ray Computed ,Biomarkers ,Food Science - Abstract
Renal dysfunction and sarcopenia are important prognostic factors in patients with chronic liver disease (CLD). Muscle atrophy can cause the overestimation of renal function based on serum creatinine. However, the frequency of overestimated renal function in Japanese patients with CLD and its relationship with sarcopenia are unclear. In present study, we evaluated the frequency of overestimated renal function, defined as a >, 20% higher eGFR using creatinine than using cystatin C, in 307 patients with CLD as well as its relationship with indicators of sarcopenia. In total, 24.8% of patients had overestimated renal function. In a multivariate regression analysis, liver cirrhosis (p = 0.004) and psoas muscle mass index (p = 0.049) were significantly associated with overestimated renal function. Loss of skeletal muscle mass was significantly more frequent in both male and female patients with overestimated renal function than without. In males, the loss of muscle strength and rate of sarcopenia, defined as loss of muscle mass and strength, were significantly higher in patients with than without overestimated renal function. The high frequency of overestimated renal function in Japanese patients suggests that indicators of renal function should be carefully considered, furthermore, monitoring and interventions for both renal function and sarcopenia are needed in patients with CLD.
- Published
- 2021
50. Effects of resistance‐associated variants in genotype 2 hepatitis C virus on viral replication and susceptibility to antihepatitis C virus drugs
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Megumi Kimura, Takuya Sho, Kenichi Morikawa, Goki Suda, Masato Nakai, Koji Ogawa, Naoki Kawagishi, Tomoe Shimazaki, Taku Shigesawa, Mitsuteru Natsuizaka, Naoya Sakamoto, Masatsugu Ohara, Akihisa Nakamura, Osamu Maehara, and Kazuharu Suzuki
- Subjects
Hepatology ,Sofosbuvir ,medicine.drug_class ,viruses ,Ribavirin ,Hepatitis C virus ,virus diseases ,Biology ,medicine.disease_cause ,Virology ,digestive system diseases ,Pibrentasvir ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Infectious Diseases ,chemistry ,030220 oncology & carcinogenesis ,Genotype ,medicine ,030211 gastroenterology & hepatology ,Antiviral drug ,NS5A ,NS5B ,medicine.drug - Abstract
AIMS Development of direct-acting antivirals (DAAs) has made antihepatitis C virus (HCV) treatment highly safe and effective. However, the emergence of resistant-associated variants (RAVs) after failure of DAA therapy affects retreatment outcomes. In particular, genotype 1 HCV with P32 deletion has been reported to be highly resistant to all approved non-structural protein (NS)5A inhibitors. However, analysis of RAVs in genotype 2 HCV has been limited. Accordingly, in this study, we evaluated the roles of genotype 2 HCV variants in antiviral drug efficacy. METHODS We utilized HCV-2b/2a (JFH-1) chimeric virus (genotype 2a), which replicates more robustly than JFH-1. We constructed various genotype 2a JFH-1-based HCV cell culture systems with NS3 (D168E), NS5A (F28S, F28S/M31I, P32 deletion, and Y93H), and NS5B (S282 T) RAVs and analyzed the replication ability and sensitivity to various anti-HCV reagents. RESULTS Genotype 2a-based HCV with NS5A-P32 deletion could not replicate even in long-term cultures. Genotype 2a-based HCV with NS5A-F28S/M31I showed significantly higher replication ability than the wild-type strain, and replication could not be suppressed, even with high concentrations of NS5A inhibitors, including pibrentasvir and velpatasvir (
- Published
- 2019
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