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1
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Tada T, Kurosaki M, Toyoda H, Tamaki N, Yasui Y, Nakamura S, Mori N, Tsuji K, Ochi H, Akahane T, Kobashi H, Fujii H, Marusawa H, Kondo M, Urawa N, Yoshida H, Uchida Y, Morita A, Hasebe C, Mitsuda A, Ogawa C, Narita R, Kubotsu Y, Matsushita T, Shigeno M, Okamoto E, Okada K, Kasai T, Ishii T, Nonogi M, Yasuda S, Koshiyama Y, Kumada T, Izumi N. Viral eradication reduces all-cause mortality in patients with chronic hepatitis C virus infection who had received direct-acting antiviral therapy. Liver Int 2024; 44:3060-3071. [PMID: 39223936 DOI: 10.1111/liv.16093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 08/01/2024] [Accepted: 08/22/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND AND AIMS The impact of hepatitis C virus (HCV) eradication via direct-acting antiviral (DAA) therapy on overall mortality, particularly non-liver-related mortality, is understudied. METHODS We recruited 4180 patients with chronic HCV infection who achieved sustained virological response (SVR) (HCV eradication) through DAA therapy (n = 2501, SVR group) or who did not receive antiviral therapy (n = 1679, non-SVR group); 1236 from each group were chosen using propensity score matching. Causes of death and all-cause mortality, including non-liver-related diseases, were investigated. RESULTS Of the 4180 patients, 592 died during the follow-up period. In the SVR group, the mortality rates from liver-related and non-liver-related diseases were 16.5% and 83.5%, respectively. Compared to the non-SVR group, mortality rates from liver-related and non-liver-related diseases were 50.1% and 49.9%, respectively (p < .001). In non-cirrhotic patients, multivariable analysis revealed that SVR was an independent factor associated with both liver-related (hazard ratio [HR], .251; 95% confidence interval [CI], .092-.686) and non-liver-related (HR, .641; 95% CI, .415-.990) mortalities. In cirrhotic patients, multivariable analysis revealed that SVR remained an independent factor significantly associated with liver-related mortality (HR, .151; 95% CI, .081-.279). In propensity score-matched patients, the eradication of HCV (SVR group) decreased both liver-related (p < .001) and non-liver-related mortality (p = .008) rates compared to persistent HCV infection (non-SVR group). CONCLUSIONS The elimination of HCV via DAA therapy reduced not only liver-related mortality but also non-liver-related mortality in patients with chronic HCV.
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Affiliation(s)
- Toshifumi Tada
- Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital, Himeji, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yutaka Yasui
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Shinichiro Nakamura
- Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital, Himeji, Japan
| | - Nami Mori
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Keiji Tsuji
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Hironori Ochi
- Center for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Matsuyama, Japan
| | - Takehiro Akahane
- Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Japan
| | - Haruhiko Kobashi
- Department of Gastroenterology, Japanese Red Cross Okayama Hospital, Okayama, Japan
| | - Hideki Fujii
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - Hiroyuki Marusawa
- Department of Gastroenterology and Hepatology, Japanese Red Cross Osaka Hospital, Osaka, Japan
| | - Masahiko Kondo
- Department of Gastroenterology, Japanese Red Cross Otsu Hospital, Otsu, Japan
| | - Naohito Urawa
- Department of Hepatology, Japanese Red Cross Ise Hospital, Ise, Japan
| | - Hideo Yoshida
- Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Yasushi Uchida
- Department of Gastroenterology, Japanese Red Cross Matsue Hospital, Matsue, Japan
| | - Atsuhiro Morita
- Department of Gastroenterology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan
| | - Chitomi Hasebe
- Department of Gastroenterology, Japanese Red Cross Asahikawa Hospital, Asahikawa, Japan
| | - Akeri Mitsuda
- Department of Gastroenterology, Tottori Red Cross Hospital, Tottori, Japan
| | - Chikara Ogawa
- Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan
| | - Ryoichi Narita
- Department of Gastroenterology, Oita Red Cross Hospital, Oita, Japan
| | - Yoshihito Kubotsu
- Department of Internal Medicine, Karatsu Red Cross Hospital, Saga, Japan
| | | | - Masaya Shigeno
- Department of Gastroenterology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan
| | - Eisuke Okamoto
- Department of Gastroenterology, Masuda Red Cross Hospital, Masuda, Japan
| | - Kazuhiko Okada
- Department of Gastroenterology, Toyama Red Cross Hospital, Toyama, Japan
| | - Toyotaka Kasai
- Department of Gastroenterology, Fukaya Red Cross Hospital, Saitama, Japan
| | - Toru Ishii
- Department of Gastroenterology, Japanese Red Cross Akita Hospital, Akita, Japan
| | - Michiko Nonogi
- Department of Gastroenterology, Tokushima Red Cross Hospital, Tokushima, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan
| | - Yuichi Koshiyama
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Gifu, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
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Tada T, Kumada T, Hiraoka A, Kariyama K, Yasuda S, Tada F, Ohama H, Nouso K, Matono T, Nakamura S, Toyoda H. mADRES predicts hepatocellular carcinoma development in patients with hepatitis C virus who achieved sustained virological response. J Gastroenterol Hepatol 2024; 39:1164-1171. [PMID: 38403468 DOI: 10.1111/jgh.16512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 12/30/2023] [Accepted: 01/31/2024] [Indexed: 02/27/2024]
Abstract
BACKGROUND AND AIM The study aims to develop a novel predictive model including the fibrosis (FIB)-3 index for hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C virus (HCV) who achieved sustained virological response (SVR) with direct-acting antiviral (DAA) therapy. METHODS This study included 2529 patients in whom HCV was eradicated with DAA therapy. The after DAA recommendation for surveillance (ADRES) score, which is based on sex, FIB-4 index, and α-fetoprotein, was used to predict HCC development. We developed a modified ADRES (mADRES) score, in which the FIB-4 index was replaced by the FIB-3 index, and evaluated its usefulness in predicting HCC development compared with the ADRES score. RESULTS In the training set (n = 1770), multivariate analysis with Cox proportional hazards modeling showed that male sex (hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.48-3.01), FIB-3 index (HR, 1.36; 95% CI, 1.28-1.45), and α-fetoprotein (HR, 1.05; 95% CI, 1.03-1.07) are independently associated with HCC development. The incidence of HCC differed significantly by ADRES or mADRES score in multiple comparisons. Univariate Cox proportional hazards models showed that compared with the mADRES score 0 group, the HR for HCC development was 2.07 (95% CI, 1.02-4.19) for the mADRES score 1 group, 11.37 (95% CI, 5.80-22.27) for the mADRES score 2 group, and 21.95 (95% CI, 10.17-47.38) for the mADRES score 3 group. Similar results were obtained for mADRES score but not for ADRES score in the validation set (n = 759). CONCLUSION The mADRES score is useful for predicting HCC development after SVR.
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Affiliation(s)
- Toshifumi Tada
- Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital, Himeji, Japan
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Gifu, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Kazuya Kariyama
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Fujimasa Tada
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Hideko Ohama
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Kazuhiro Nouso
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Tomomitsu Matono
- Department of Internal Medicine, Himeji St. Mary's Hospital, Himeji, Japan
- Department of Gastroenterology, Hyogo Prefectural Harima-Himeji General Medical Center, Himeji, Japan
| | - Shinichiro Nakamura
- Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital, Himeji, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
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3
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Morita A, Tamaki N, Kobashi H, Mori N, Tsuji K, Takaki S, Hasebe C, Akahane T, Ochi H, Mashiba T, Urawa N, Fujii H, Mitsuda A, Kondo M, Ogawa C, Uchida Y, Narita R, Marusawa H, Kubotsu Y, Matsushita T, Shigeno M, Yoshida H, Tanaka K, Okamoto E, Kasai T, Ishii T, Okada K, Kurosaki M, Izumi N. Effect of treatment periods on efficacy of glecaprevir and pibrentasvir in chronic hepatitis C: A nationwide, prospective, multicenter study. JGH Open 2024; 8:e13068. [PMID: 38681824 PMCID: PMC11046085 DOI: 10.1002/jgh3.13068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 03/26/2024] [Accepted: 04/03/2024] [Indexed: 05/01/2024]
Abstract
Background and aim In patients with chronic hepatitis C, 8 weeks of glecaprevir and pibrentasvir (GLE/PIB) treatment for chronic hepatitis (non-cirrhosis) and 12 weeks for cirrhosis have been approved in Japan. However, whether 8 weeks of treatment for cirrhosis may reduce treatment efficacy has not been adequately investigated. Methods This prospective, nationwide, multicenter cohort study enrolled 1275 patients with chronic hepatitis C who received GLE/PIB therapy. The effect of liver fibrosis and treatment periods on the efficiency of GLE/PIB therapy was investigated. The primary endpoint was the sustained virological response (SVR) rate in patients with chronic hepatitis (non-cirrhosis) and cirrhosis. The association between treatment periods and liver fibrosis on the SVR after 12 weeks of treatment rate was investigated. Results The SVR rates in patients with chronic hepatitis with 8 weeks of treatment, chronic hepatitis with 12 weeks of treatment, cirrhosis with 8 weeks of treatment, and cirrhosis with 12 weeks of treatment were 98.9% (800/809), 100% (87/87), 100% (166/166), and 99.1% (211/213), respectively, and were was not different among these groups (P = 0.4). Conclusion GLE/PIB therapy for chronic hepatitis C had high efficacy regardless of liver fibrosis status and treatment periods. Periods of GLE/PIB therapy could be chosen with available modalities, and high SVR rates could be achieved regardless of the decision.
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Affiliation(s)
- Atsuhiro Morita
- Department of GastroenterologyJapanese Red Cross Kyoto Daini HospitalKyotoJapan
| | - Nobuharu Tamaki
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Haruhiko Kobashi
- Department of GastroenterologyJapanese Red Cross Okayama HospitalOkayamaJapan
| | - Nami Mori
- Department of GastroenterologyHiroshima Red Cross Hospital & Atomic‐bomb Survivors HospitalHiroshimaJapan
| | - Keiji Tsuji
- Department of GastroenterologyHiroshima Red Cross Hospital & Atomic‐bomb Survivors HospitalHiroshimaJapan
| | - Shintaro Takaki
- Department of GastroenterologyHiroshima Red Cross Hospital & Atomic‐bomb Survivors HospitalHiroshimaJapan
| | - Chitomi Hasebe
- Department of GastroenterologyJapanese Red Cross Asahikawa HospitalAsahikawaJapan
| | - Takehiro Akahane
- Department of GastroenterologyIshinomaki Red Cross HospitalIshinomakiJapan
| | - Hironori Ochi
- Center for Liver‐Biliary‐Pancreatic DiseaseMatsuyama Red Cross HospitalMatsuyamaJapan
| | - Toshie Mashiba
- Center for Liver‐Biliary‐Pancreatic DiseaseMatsuyama Red Cross HospitalMatsuyamaJapan
| | - Naohito Urawa
- Department of Gastroenterology and HepatologyIse Red Cross HospitalIseJapan
| | - Hideki Fujii
- Department of GastroenterologyJapanese Red Cross Kyoto Daiichi HospitalKyotoJapan
| | - Akeri Mitsuda
- Department of GastroenterologyTottori Red Cross HospitalTottoriJapan
| | - Masahiko Kondo
- Department of GastroenterologyOtsu Red Cross HospitalOtsuJapan
| | - Chikara Ogawa
- Department of Gastroenterology and HepatologyTakamatsu Red Cross HospitalTakamatsuJapan
| | - Yasushi Uchida
- Department of GastroenterologyMatsue Red Cross HospitalMatsueJapan
| | - Ryoichi Narita
- Department of GastroenterologyOita Red Cross HospitalOitaJapan
| | - Hiroyuki Marusawa
- Department of Gastroenterology and HepatologyOsaka Red Cross HospitalOsakaJapan
| | | | | | - Masaya Shigeno
- Department of GastroenterologyJapanese Red Cross Nagasaki Genbaku HospitalNagasakiJapan
| | - Hideo Yoshida
- Department of GastroenterologyJapanese Red Cross Medical CenterTokyoJapan
| | - Katsuaki Tanaka
- Department of GastroenterologyHatano Red Cross HospitalHatanoJapan
| | - Eisuke Okamoto
- Department of GastroenterologyMasuda Red Cross HospitalMasudaJapan
| | - Toyotaka Kasai
- Department of GastroenterologyFukaya Red Cross HospitalSaitamaJapan
| | - Toru Ishii
- Department of GastroenterologyJapanese Red Cross Akita HospitalAkitaJapan
| | - Kazuhiko Okada
- Department of GastroenterologyToyama Red Cross HospitalToyamaJapan
| | - Masayuki Kurosaki
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Namiki Izumi
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
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4
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Ishido S, Tamaki N, Kurosaki M, Mori N, Tsuji K, Hasebe C, Mashiba T, Ochi H, Yasui Y, Akahane T, Furuta K, Kobashi H, Fujii H, Ishii T, Marusawa H, Kondo M, Kusakabe A, Yoshida H, Uchida Y, Tada T, Nakamura S, Mitsuda A, Ogawa C, Arai H, Murohisa T, Uebayashi M, Izumi N. Necessity for surveillance for hepatocellualr carcinoma in older patients with chronic hepatitis C who achieved sustained virological response. JGH Open 2023; 7:424-430. [PMID: 37359109 PMCID: PMC10290273 DOI: 10.1002/jgh3.12914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 04/29/2023] [Accepted: 05/11/2023] [Indexed: 06/28/2023]
Abstract
Background and Aim Hepatocellular carcinoma (HCC) surveillance in low-risk patients (annual incidence <1.5%) is not recommended per the American Association for the Study of Liver Diseases guidelines. Because patients with chronic hepatitis C with non-advanced fibrosis who have achieved sustained virological response (SVR) have a low risk of HCC, HCC surveillance is not recommended for them. However, aging is a risk factor for HCC; threfore, the necessity for HCC surveillance in older patients with non-advanced fibrosis needs to be verified. Methods This multicenter, prospective study enrolled 4993 patients with SVR (1998 patients with advanced fibrosis and 2995 patients with non-advanced fibrosis). The HCC incidence was examined with particular attention to age. Results The 3-year incidence of HCC in patients with advanced and non-advanced fibrosis was 9.2% (95% CI: 7.8-10.9) and 2.9% (95% CI: 2.1-3.7), respectively. HCC incidence was significantly higher in patients with advanced fibrosis (P < 0.001). HCC incidence stratified by age and sex was investigated in patients with non-advanced fibrosis. The HCC incidence in the 18-49, 50s, 60s, 70s, and ≥80 age groups were 0.26, 1.3, 1.8, 1.7, and 2.9 per 100 person-years in men, and 0.00, 0.32, 0.58, 0.49, and 0.57 per 100 person-years in women, respectively. Conclusions Male patients with non-advanced fibrosis aged ≥60 years have a higher risk of developing HCC and, thus, require HCC surveillance.
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Affiliation(s)
- Shun Ishido
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Nobuharu Tamaki
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Masayuki Kurosaki
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Nami Mori
- Department of GastroenterologyHiroshima Red Cross Hospital and Atomic Bomb Survivors' HospitalHiroshimaJapan
| | - Keiji Tsuji
- Department of GastroenterologyHiroshima Red Cross Hospital and Atomic Bomb Survivors' HospitalHiroshimaJapan
| | - Chitomi Hasebe
- Department of GastroenterologyAsahikawa Red Cross HospitalAsahikawaJapan
| | - Toshie Mashiba
- Center for Liver‐Biliary‐Pancreatic DiseaseMatsuyama Red Cross HospitalMatsuyamaJapan
| | - Hironori Ochi
- Center for Liver‐Biliary‐Pancreatic DiseaseMatsuyama Red Cross HospitalMatsuyamaJapan
| | - Yutaka Yasui
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Takehiro Akahane
- Department of GastroenterologyIshinomaki Red Cross HospitalIshinomakiJapan
| | - Koichiro Furuta
- Department of GastroenterologyMasuda Red Cross HospitalMasudaJapan
| | - Haruhiko Kobashi
- Department of GastroenterologyJapanese Red Cross Okayama HospitalOkayamaJapan
| | - Hideki Fujii
- Department of GastroenterologyJapanese Red Cross Kyoto Daiichi HospitalKyotoJapan
| | - Toru Ishii
- Department of GastroenterologyJapanese Red Cross Akita HospitalAkitaJapan
| | - Hiroyuki Marusawa
- Department of Gastroenterology and HepatologyOsaka Red Cross HospitalOsakaJapan
| | - Masahiko Kondo
- Department of GastroenterologyOtsu Red Cross HospitalOtsuJapan
| | - Atsunori Kusakabe
- Department of GastroenterologyJapanese Red Cross Aichi Medical Center Nagoya Daini HospitalNagoyaJapan
| | - Hideo Yoshida
- Department of GastroenterologyJapanese Red Cross Medical CenterTokyoJapan
| | - Yasushi Uchida
- Department of GastroenterologyMatsue Red Cross HospitalMatsueJapan
| | - Toshifumi Tada
- Department of Internal MedicineHimeji Red Cross HospitalHimejiJapan
| | | | - Akari Mitsuda
- Department of GastroenterologyTottori Red Cross HospitalTottoriJapan
| | - Chikara Ogawa
- Department of GastroenterologyTakamatsu Red Cross HospitalTakamatsuJapan
| | - Hirotaka Arai
- Department of GastroenterologyMaebashi Red Cross HospitalMaebashiJapan
| | - Toshimitsu Murohisa
- Department of GastroenterologyJapanese Red Cross Ashikaga HospitalAshikagaJapan
| | - Minoru Uebayashi
- Department of GastroenterologyKitami Red Cross HospitalKitamiJapan
| | - Namiki Izumi
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
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5
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Tahata Y, Sakamori R, Maesaka K, Doi A, Yamada R, Kodama T, Hikita H, Miyazaki M, Nozaki Y, Kaneko A, Oshita M, Tanaka S, Imanaka K, Hiramatsu N, Morishita N, Ohkawa K, Yakushijin T, Sakakibara M, Iio S, Doi Y, Tatsumi T, Takehara T. Effect of sofosbuvir and velpatasvir therapy on clinical outcome in hepatitis C virus patients with decompensated cirrhosis. Hepatol Res 2022; 53:301-311. [PMID: 36507871 DOI: 10.1111/hepr.13868] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 12/07/2022] [Accepted: 12/09/2022] [Indexed: 02/08/2023]
Abstract
AIM To determine the impact of direct-acting antiviral therapy on the long-term prognosis of decompensated cirrhotic patients. METHODS A total of 37 patients with hepatitis C virus-induced decompensated cirrhosis treated with sofosbuvir and velpatasvir (SOF/VEL group) were prospectively enrolled. For historical control, 65 hepatitis C virus-positive decompensated cirrhotic patients who did not receive direct-acting antiviral therapy were included (control group). The incidence rates of hepatocellular carcinoma (HCC), decompensated events with hospitalization, and overall survival were compared between both groups. RESULTS A total of 41 patients experienced decompensated events during 15.0 months in the control group, and six patients during 21.6 months in the SOF/VEL group. The cumulative incidence rates of decompensated events after 2 years were significantly higher in the control group (53.1%) than in the SOF/VEL group (14.5%; p < 0.001). A total of 27 patients died within 22.0 months in the control group, and three patients died within 25.6 months in the SOF/VEL group. The overall survival rates after 2 years were significantly lower in the control group (67.6%) than in the SOF/VEL group (91.3%; p = 0.010). A total of 13 patients in the control group developed HCC during 15.8 months, and 10 patients during 17.3 months in the SOF/VEL group. The HCC incidence rates after 2 years were 20.3% and 29.6% in the control and SOF/VEL groups, respectively, with no significant difference (p = 0.327). CONCLUSIONS SOF/VEL therapy may suppress the development of decompensated events and improve the prognosis in decompensated cirrhotic patients; however, the incidence of HCC remains prevalent in these patients irrespective of SOF/VEL therapy.
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Affiliation(s)
- Yuki Tahata
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Ryotaro Sakamori
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Kazuki Maesaka
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Akira Doi
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Ryoko Yamada
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Takahiro Kodama
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Hayato Hikita
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | | | | | - Akira Kaneko
- Japan Community Healthcare Organization Osaka Hospital, Osaka, Japan
| | | | - Satoshi Tanaka
- National Hospital Organization Osaka National Hospital, Osaka, Japan
| | | | | | | | | | | | | | - Sadaharu Iio
- Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
| | | | - Tomohide Tatsumi
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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6
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Mita E, Liu LJ, Shing D, Force L, Aoki K, Nakamoto D, Ishizaki A, Konishi H, Mizutani H, Ng LJ. Real-world Safety and Effectiveness of 24-week Sofosbuvir and Ribavirin Treatment in Patients Infected with Rare Chronic Hepatitis C Virus Genotypes 3, 4, 5, or 6 in Japan. Intern Med 2022; 62:1405-1414. [PMID: 36047126 DOI: 10.2169/internalmedicine.0067-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Objectives Real-world evidence on the safety and effectiveness of direct-acting antivirals in patients infected with chronic hepatitis C virus (HCV) genotypes (GTs) 3, 4, 5, or 6 in Japan is limited. This prospective observational study assesses the real-world safety profile and treatment effectiveness among patients prescribed sofosbuvir with ribavirin (SOF+RBV) for HCV GT3-6 infection in Japan. Methods Adults receiving 24-week SOF+RBV treatment for HCV GT3-6 infection were prospectively enrolled and observed through 24 weeks post-treatment for treatment-emergent adverse events (AEs) considered related to SOF and/or RBV by treating physicians and for a sustained virologic response at 12 and 24 weeks post-treatment (SVR12, SVR24). Incidence rates of related AEs and serious AEs (SAEs) were calculated. Proportions of patients experiencing related AEs/SAEs and those achieving SVR12 and SVR24 were assessed overall and by baseline characteristics, including treatment experience and cirrhosis status. Results Among the 50 patients included in the safety analysis, 92% had GT3 infection. The incidence rates of related AEs and SAEs were low overall (1.52 and 0.25 per 100 person-weeks, respectively), with 6.0% and 14.0% patients experiencing AEs related to SOF or RBV, respectively. There were no marked differences in the occurrence of related AEs/SAEs by patient baseline characteristics. SVR12 and SVR24 were achieved in 83.7% (41/49) and 82.2% (37/45) of patients, respectively. Lower effectiveness was observed among treatment-experienced patients and patients with cirrhosis at baseline. Conclusions This study demonstrated that SOF+RBV treatment for HCV GT3-6 infection was safe, effective, and an important treatment option for this difficult-to-treat patient population in Japan.
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Affiliation(s)
- Eiji Mita
- National Hospital Organization Osaka National Hospital, Japan
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7
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Tada T, Kurosaki M, Tamaki N, Yasui Y, Mori N, Tsuji K, Hasebe C, Joko K, Akahane T, Furuta K, Kobashi H, Fujii H, Ishii T, Marusawa H, Kondo M, Kojima Y, Yoshida H, Uchida Y, Nakamura S, Izumi N. General evaluation score
for predicting the development of
hepatocellular carcinoma
in patients with advanced liver fibrosis associated with
hepatitis C virus
genotype 1 or 2 after
direct‐acting antiviral
therapy. JGH Open 2022; 6:487-495. [PMID: 35822118 PMCID: PMC9260214 DOI: 10.1002/jgh3.12778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 05/05/2022] [Accepted: 05/24/2022] [Indexed: 11/28/2022]
Abstract
Background and Aim To validate a composite predictive model for hepatocellular carcinoma (HCC) development in patients with advanced liver fibrosis associated with chronic hepatitis C virus (HCV) who have received direct‐acting antiviral (DAA) therapy and achieved sustained virologic response (SVR). Methods This study included 1258 patients with advanced liver fibrosis associated with HCV genotype 1, 2, or both. General evaluation score (GES), which is based on sex, age, fibrosis stage, albumin, and α‐fetoprotein, was used as a composite predictive model. Results There were 645 (51.3%) patients in the low‐risk group, 228 (18.1%) in the intermediate‐risk group, and 385 (30.6%) in the high‐risk group based on GES categories. The 12‐, 36‐, and 60‐month cumulative incidence of HCC was 0.7%, 5.3%, and 13.0%, respectively. Multivariable analysis with Cox proportional hazards models showed that male sex (hazard ratio [HR], 1.863; 95% confidence interval [CI], 1.204–2.883), F4 fibrosis stage (HR, 3.199; 95% CI, 1.696–6.036), and albumin (HR, 0.489; 95% CI, 0.288–0.828) are independently associated with HCC development. The incidence of HCC differed significantly by GES‐based risk category (P < 0.001). Cox proportional hazards models showed that, with the low‐risk group as the referent, the HR for HCC development was 1.875 (95% CI, 1.000–3.514) in the intermediate‐risk group and 2.819 (95% CI, 1.716–4.630) in the high‐risk group. GES had better predictive ability for HCC development than fibrosis‐4 index according to time‐dependent receiver operating characteristic analysis. Conclusion GES is useful for predicting HCC development in patients with advanced liver fibrosis after SVR.
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Affiliation(s)
- Toshifumi Tada
- Department of Internal Medicine Japanese Red Cross Society Himeji Hospital Himeji Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Yutaka Yasui
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Nami Mori
- Department of Gastroenterology Hiroshima Red Cross Hospital and Atomic‐Bomb Survivors Hospital Hiroshima Japan
| | - Keiji Tsuji
- Department of Gastroenterology Hiroshima Red Cross Hospital and Atomic‐Bomb Survivors Hospital Hiroshima Japan
| | - Chitomi Hasebe
- Department of Gastroenterology Japanese Red Cross Asahikawa Hospital Asahikawa Japan
| | - Koji Joko
- Center for Liver‐Biliary‐Pancreatic Disease Matsuyama Red Cross Hospital Matsuyama Japan
| | - Takehiro Akahane
- Department of Gastroenterology Japanese Red Cross Ishinomaki Hospital Ishinomaki Japan
| | - Koichiro Furuta
- Department of Gastroenterology Masuda Red Cross Hospital Masuda Japan
| | - Haruhiko Kobashi
- Department of Gastroenterology Japanese Red Cross Okayama Hospital Okayama Japan
| | - Hideki Fujii
- Department of Gastroenterology Japanese Red Cross Kyoto Daiichi Hospital Kyoto Japan
| | - Toru Ishii
- Department of Gastroenterology Japanese Red Cross Akita Hospital Akita Japan
| | - Hiroyuki Marusawa
- Department of Gastroenterology and Hepatology Japanese Red Cross Osaka Hospital Osaka Japan
| | - Masahiko Kondo
- Department of Gastroenterology Japanese Red Cross Otsu Hospital Otsu Shiga Japan
| | - Yuji Kojima
- Department of Hepatology Japanese Red Cross Ise Hospital Ise Japan
| | - Hideo Yoshida
- Department of Gastroenterology Japanese Red Cross Medical Center Tokyo Japan
| | - Yasushi Uchida
- Department of Gastroenterology Japanese Red Cross Matsue Hospital Matsue Japan
| | - Shinichiro Nakamura
- Department of Internal Medicine Japanese Red Cross Society Himeji Hospital Himeji Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
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8
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Nakajima T, Karino Y, Hige S, Suii H, Tatsumi R, Yamaguchi M, Arakawa T, Kuwata Y, Toyota J. Aging impairs fibrosis-4 index after sustained virologic response by direct-acting antivirals in chronic hepatitis C infection. Ann Hepatol 2022; 27:100566. [PMID: 34688887 DOI: 10.1016/j.aohep.2021.100566] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Revised: 09/18/2021] [Accepted: 09/27/2021] [Indexed: 02/08/2023]
Abstract
INTRODUCTION AND OBJECTIVES Sustained virologic response (SVR) is achieved in most cases of C-type liver disease after direct-acting antiviral (DAA) therapy. Although liver fibrosis improves, the degree of improvement is different. This study aimed to analyze the factors involved in improving liver fibrosis using the fibrosis 4 (FIB-4) index. MATERIAL AND METHODS Patients were monitored for >3 years after SVR. At the start of therapy (SOT), liver fibrosis was categorized as either mild (<1.45 n = 28), moderate (1.45-3.25 n = 139), or advanced (>3.25 n = 236) based on the FIB-4 index. The FIB-4 index in the advanced group decreased significantly compared to that of the other two, so we selected the advanced group as the analysis target. SOT and end of therapy (EOT) factors that contributed to the FIB-4 index ≤3.25 at 3 years after therapy were examined using a multivariate analysis. RESULTS Among the SOT factors, age (<72 years old), absence of liver cirrhosis (LC), alanine transferase (ALT) (≥50 U/L), platelet (PLT) (≥10.2 × 104/mm3), and total bilirubin (T.Bil) (<0.8 mg/dl) were the significant factors contributing to the improvement of the FIB-4 index. Among the EOT factors, age (<72 years), PLT (≥12.0 × 104/mm3), and hemoglobin (Hb) (≥12.1 g/dl) were the significant factors contributing to the improvement of FIB-4 index. CONCLUSIONS Factors involved in the improvement of liver fibrosis after SVR were young age, absence of LC, low T.Bil., high ALT, high PLT, and high Hb levels. The levels of T.Bil, PLT, and Hb were considered to be related to portal hypertension. Aging strongly impaired the improvement in liver fibrosis.
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Affiliation(s)
- Tomoaki Nakajima
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Yoshiyasu Karino
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan; Department of Gastroenterology, Keiyukai Sapporo Hospital, Sapporo, Japan.
| | - Shuhei Hige
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Hirokazu Suii
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Ryoji Tatsumi
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | | | - Tomohiro Arakawa
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Yasuaki Kuwata
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Joji Toyota
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
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9
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Tamaki N, Kurosaki M, Yasui Y, Mori N, Tsuji K, Hasebe C, Joko K, Akahane T, Furuta K, Kobashi H, Kimura H, Yagisawa H, Marusawa H, Kondo M, Kojima Y, Yoshida H, Uchida Y, Tada T, Nakamura S, Yasuda S, Toyoda H, Loomba R, Izumi N. Hepatocellular Carcinoma Risk Assessment for Patients With Advanced Fibrosis After Eradication of Hepatitis C Virus. Hepatol Commun 2022; 6:461-472. [PMID: 34676692 PMCID: PMC8870028 DOI: 10.1002/hep4.1833] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The identification of patients with advanced fibrosis who do not need any further hepatocellular carcinoma (HCC) surveillance after the eradication of hepatitis C is pivotal. In this study, we developed a simple serum-based risk model that could identify patients with low-risk HCC. This was a nationwide multicenter study involving 16 Hospitals in Japan. Patients with advanced fibrosis (1,325 in a derivation cohort and 508 in a validation cohort) who achieved sustained virological responses at 24 weeks after treatment (SVR24) were enrolled. The HCC risk model at any point after SVR24 and its change were evaluated, and subsequent HCC development was analyzed. Based on the multivariable analysis, patients fulfilling all of the factors (GAF4 criteria: gamma-glutamyl transferase < 28 IU/L, alpha-fetoprotein < 4.0 ng/mL, and Fibrosis-4 Index < 4.28) were classified as low-risk and others were classified as high-risk. When patients were stratified at the SVR24, and 1 year, and 2 years after SVR24, subsequent HCC development was significantly lower in low-risk patients (0.5-1.1 per 100 person-years in the derivation cohort and 0.9-1.1 per 100 person-years in the validation cohort) than in high-risk patients at each point. HCC risk from 1 year after SVR24 decreased in patients whose risk improved from high-risk to low-risk (HCC incidence: 0.6 per 100 person-years [hazard ratio (HR) = 0.163 in the derivation cohort] and 1.3 per 100 person-years [HR = 0.239 in the validation cohort]) than in those with sustained high risk. Conclusion: The HCC risk model based on simple serum markers at any point after SVR and its change can identify patients with advanced fibrosis who are at low HCC risk, and these patients may be able to reduce HCC surveillance.
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Affiliation(s)
- Nobuharu Tamaki
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan.,NAFLD Research CenterDivision of Gastroenterology and HepatologyDepartment of MedicineUniversity of California San DiegoLa JollaCaliforniaUSA
| | - Masayuki Kurosaki
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Yutaka Yasui
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Nami Mori
- Department of GastroenterologyHiroshima Red Cross Hospital and Atomic-bomb Survivors HospitalHiroshimaJapan
| | - Keiji Tsuji
- Department of GastroenterologyHiroshima Red Cross Hospital and Atomic-bomb Survivors HospitalHiroshimaJapan
| | - Chitomi Hasebe
- Department of GastroenterologyJapanese Red Cross Asahikawa HospitalAsahikawaHokkaidoJapan
| | - Kouji Joko
- Center for Liver-Biliary-Pancreatic DiseaseMatsuyama Red Cross HospitalMatsuyamaEhimeJapan
| | - Takehiro Akahane
- Department of GastroenterologyJapanese Red Cross Ishinomaki HospitalIshinomakiMiyagiJapan
| | - Koichiro Furuta
- Department of GastroenterologyMasuda Red Cross HospitalMasudaShimaneJapan
| | - Haruhiko Kobashi
- Department of GastroenterologyJapanese Red Cross Okayama HospitalOkayamaOkayamaJapan
| | - Hiroyuki Kimura
- Department of GastroenterologyJapanese Red Cross Kyoto Daiichi HospitalKyotoJapan
| | - Hitoshi Yagisawa
- Department of GastroenterologyJapanese Red Cross Akita HospitalAkitaJapan
| | - Hiroyuki Marusawa
- Department of Gastroenterology and HepatologyOsaka Red Cross HospitalOsakaJapan
| | - Masahiko Kondo
- Department of GastroenterologyJapanese Red Cross Otsu HospitalOtsuShigaJapan
| | - Yuji Kojima
- Department of HepatologyJapanese Red Cross Ise HospitalIseMieJapan
| | - Hideo Yoshida
- Department of GastroenterologyJapanese Red Cross Medical CenterTokyoJapan
| | - Yasushi Uchida
- Department of GastroenterologyMatsue Red Cross HospitalMatsueShimaneJapan
| | - Toshifumi Tada
- Department of Internal MedicineJapanese Red Cross Society Himeji HospitalHimejiJapan
| | - Shinichiro Nakamura
- Department of Internal MedicineJapanese Red Cross Society Himeji HospitalHimejiJapan
| | - Satoshi Yasuda
- Department of Gastroenterology and HepatologyOgaki Municipal HospitalOgakiJapan
| | - Hidenori Toyoda
- Department of Gastroenterology and HepatologyOgaki Municipal HospitalOgakiJapan
| | - Rohit Loomba
- NAFLD Research CenterDivision of Gastroenterology and HepatologyDepartment of MedicineUniversity of California San DiegoLa JollaCaliforniaUSA
| | - Namiki Izumi
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
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10
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Tada T, Kurosaki M, Tamaki N, Yasui Y, Mori N, Tsuji K, Hasebe C, Joko K, Akahane T, Furuta K, Kobashi H, Kimura H, Yagisawa H, Marusawa H, Kondo M, Kojima Y, Yoshida H, Uchida Y, Nakamura S, Izumi N. A validation study of after direct-acting antivirals recommendation for surveillance score for the development of hepatocellular carcinoma in patients with hepatitis C virus infection who had received direct-acting antiviral therapy and achieved sustained virological response. JGH Open 2022; 6:20-28. [PMID: 35071784 PMCID: PMC8762616 DOI: 10.1002/jgh3.12690] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 11/25/2021] [Accepted: 11/28/2021] [Indexed: 12/19/2022]
Abstract
Background and Aim The pathogenic process underlying the development of hepatocellular carcinoma (HCC) is not yet clear in patients with hepatitis C virus (HCV) who have received direct-acting antiviral (DAA) therapy and achieved sustained virological response (SVR). This study validated a composite predictive model for HCC in these patients. Methods This study included 3058 patients in whom HCV was eradicated with DAA therapy. After DAAs recommendation for surveillance (ADRES) score, which is based on sex, FIB-4 index, and α-fetoprotein, was used as a composite predictive model for HCC development. Results The 1-, 3-, and 5-year cumulative incidence rates of HCC were 0.9, 4.5, and 15.2%, respectively. Multivariate analysis with Cox proportional hazards models showed that male sex (hazard ratio [HR], 2.646; 95% confidence interval [CI], 1.790-3.911), FIB-4 index >3.25 (HR, 2.891; 95% CI, 1.947-4.293), and α-fetoprotein >5 ng/mL (HR, 2.835; 95% CI, 1.914-4.200) are independently associated with HCC development. The incidence of HCC differed significantly by ADRES score (P < 0.001). Cox proportional hazards models showed that compared to the ADRES score 0 group, the HR for HCC development was 2.947 (95% CI, 1.367-6.354) in the ADRES score 1 group, 9.171 (95% CI, 4.339-19.380) in the ADRES score 2 group, and 20.630 (95% CI, 8.641-49.230) in the ADRES score 3 group. ADRES score had superior predictive power for HCC development compared with the FIB-4 index and α-fetoprotein according to time-dependent receiver operating characteristic analysis. Conclusion The ADRES score is useful for predicting HCC development after SVR.
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Affiliation(s)
- Toshifumi Tada
- Department of Internal Medicine Japanese Red Cross Society Himeji Hospital Himeji Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Yutaka Yasui
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Nami Mori
- Department of Gastroenterology Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital Hiroshima Hiroshima Japan
| | - Keiji Tsuji
- Department of Gastroenterology Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital Hiroshima Hiroshima Japan
| | - Chitomi Hasebe
- Department of Gastroenterology Japanese Red Cross Asahikawa Hospital Asahikawa Hokkaido Japan
| | - Koji Joko
- Center for Liver-Biliary-Pancreatic Disease Matsuyama Red Cross Hospital Matsuyama Ehime Japan
| | - Takehiro Akahane
- Department of Gastroenterology Japanese Red Cross Ishinomaki Hospital Ishinomaki Miyagi Japan
| | - Koichiro Furuta
- Department of Gastroenterology Masuda Red Cross Hospital Masuda Shimane Japan
| | - Haruhiko Kobashi
- Department of Gastroenterology Japanese Red Cross Okayama Hospital Okayama Okayama Japan
| | - Hiroyuki Kimura
- Department of Gastroenterology Japanese Red Cross Kyoto Daiichi Hospital Kyoto Japan
| | - Hitoshi Yagisawa
- Department of Gastroenterology Japanese Red Cross Akita Hospital Akita Akita Japan
| | - Hiroyuki Marusawa
- Department of Gastroenterology and Hepatology Japanese Red Cross Osaka Hospital Osaka Japan
| | - Masahiko Kondo
- Department of Gastroenterology Japanese Red Cross Otsu Hospital Otsu Shiga Japan
| | - Yuji Kojima
- Department of Hepatology Japanese Red Cross Ise Hospital Ise Mie Japan
| | - Hideo Yoshida
- Department of Gastroenterology Japanese Red Cross Medical Center Tokyo Japan
| | - Yasushi Uchida
- Department of Gastroenterology Japanese Red Cross Matsue Hospital Matsue Shimane Japan
| | - Shinichiro Nakamura
- Department of Internal Medicine Japanese Red Cross Society Himeji Hospital Himeji Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
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11
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Tahata Y, Sakamori R, Takehara T. Treatment progress and expansion in Japan: From interferon to direct-acting antiviral. Glob Health Med 2021; 3:321-334. [PMID: 34782876 DOI: 10.35772/ghm.2021.01083] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 08/24/2021] [Accepted: 09/10/2021] [Indexed: 12/17/2022]
Abstract
Hepatitis C virus (HCV) was first discovered in 1989, and patients infected with HCV were initially treated with interferon (IFN) monotherapy. In the 2000s, pegylated IFN combined with ribavirin was the mainstay of therapy for infected patients, but the sustained virologic response (SVR) rate was less than 50% for patients with HCV genotype 1. To further improve the therapeutic effect, direct-acting antiviral (DAA) was developed, and combination therapy with DAA and IFN has been available since 2011. In addition, IFN-free DAA therapy became available in 2014, and SVR was achieved in more than 95% of patients with chronic hepatitis and compensated cirrhosis. Thus, in just 30 years since the discovery of HCV, we aim to eliminate HCV in almost all patients. However, there are remaining issues to be addressed. Many of the patients who achieved SVR with DAA therapy had advanced liver fibrosis, and it is necessary to verify to what extent DAA therapy improves their prognosis in terms of liver function, hepatocellular carcinoma occurrence, and mortality. Resistance-associated substitutions can cause failure of DAA therapy, and the search for an effective therapy for high-level resistant viruses such as P32 deletion is particularly important. DAA therapy was approved for use in patients with decompensated cirrhosis in Japan in 2019, which is an unmet need so far. It is also important to verify the efficacy and safety in real-world settings. The World Health Organization aims to eliminate HCV by 2030, and Japan must tackle its remaining issues to achieve this goal.
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Affiliation(s)
- Yuki Tahata
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Ryotaro Sakamori
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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12
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Smirne C, D'Avolio A, Bellan M, Gualerzi A, Crobu MG, Pirisi M. Sofosbuvir-based therapies in genotype 2 hepatitis C virus cirrhosis: A real-life experience with focus on ribavirin dose. Pharmacol Res Perspect 2021; 9:e00811. [PMID: 34152088 PMCID: PMC8214994 DOI: 10.1002/prp2.811] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 05/14/2021] [Indexed: 12/05/2022] Open
Abstract
This study aimed to investigate the efficacy and safety of sofosbuvir-based therapies for the treatment of cirrhosis from hepatitis C virus (HCV) genotype 2 infection. Data of all consecutive HCV genotype 2 cirrhotic patients who started sofosbuvir-based treatments between January 2015 and March 2017 in eight Italian tertiary hospitals were collected retrospectively. Overall, 273 patients (Child A: 94.5%) were enrolled. In the 194 subjects treated with sofosbuvir/ribavirin, median initial ribavirin dosage was 13.9 mg/kg/day, and therapy duration was 16 weeks. Sustained virological response (SVR) rates were 93.8% in intention-to-treat (ITT) and 95.3% in per-protocol (PP) analyses for the 129 treatment-naïve patients, and 96.9% (ITT) and 98.4% (PP) for the 65 treatment-experienced subjects. Adverse events were reported in 142 patients (73.2%), but only 1.5% discontinued treatment. Eighty-eight subjects with treatment-induced anemia (mild: 34.5%, moderate: 7.7%, severe: 3.1%) had to reduce ribavirin dosage, but SVR rates were comparable to the weight-based dose group, both in ITT (95.4% and 94.3%) and PP (97.7% and 95.2%) analyses, respectively. Moreover, ITT and PP SVR rates were similar between shorter (<20 weeks) (94.1% and 96.0%, respectively) and prolonged (≥20 weeks) regimens (95.7% and 96.7%, respectively). SVR rates in the 79 subjects treated with sofosbuvir/daclatasvir (without ribavirin) were similar (ITT: 96.2%; PP: 97.4%, respectively), without de novo/worsening anemia. In conclusion, in a real-life study centered on genotype 2 patients with well-compensated cirrhosis, sofosbuvir-based regimens were associated with good SVR and tolerability rates, regardless of previous antiviral treatments, without a significant impact of on treatment ribavirin dose reductions.
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Affiliation(s)
- Carlo Smirne
- Internal Medicine DivisionDepartment of Translational MedicineUniversità del Piemonte OrientaleNovaraItaly
| | - Antonio D'Avolio
- Infectious Diseases UnitDepartment of Medical SciencesUniversity of TorinoTurinItaly
| | - Mattia Bellan
- Internal Medicine DivisionDepartment of Translational MedicineUniversità del Piemonte OrientaleNovaraItaly
| | | | - Maria G. Crobu
- Laboratory of Molecular VirologyMaggiore della Carità HospitalNovaraItaly
| | - Mario Pirisi
- Internal Medicine DivisionDepartment of Translational MedicineUniversità del Piemonte OrientaleNovaraItaly
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13
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Tada T, Kurosaki M, Nakamura S, Hasebe C, Kojima Y, Furuta K, Kobashi H, Kimura H, Ogawa C, Yagisawa H, Uchida Y, Joko K, Akahane T, Arai H, Marusawa H, Narita R, Ide Y, Sato T, Kusakabe A, Tsuji K, Mori N, Kondo M, Mitsuda A, Izumi N. Real-world clinical outcomes of sofosbuvir and velpatasvir treatment in HCV genotype 1- and 2-infected patients with decompensated cirrhosis: A nationwide multicenter study by the Japanese Red Cross Liver Study Group. J Med Virol 2021; 93:6247-6256. [PMID: 34170517 DOI: 10.1002/jmv.27157] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2021] [Accepted: 06/22/2021] [Indexed: 11/12/2022]
Abstract
The real-world virological efficacy and safety of interferon-free direct-acting antiviral (DAA) therapy with sofosbuvir (SOF) and velpatasvir (VEL) were assessed in hepatitis C virus (HCV) genotype 1- and 2-infected patients with decompensated cirrhosis. A total of 65 patients with HCV-related decompensated cirrhosis (Child-Pugh score of 7 points or more) who were treated with the SOF/VEL regimen were enrolled. The sustained virological response (SVR) rate and safety profile were analyzed. SVR was defined as undetectable serum HCV RNA at 12 weeks after the end of treatment (SVR12). The percentages of patients with undetectable HCV RNA at 4, 8, and 12 weeks after the start of therapy were 81.2% (95% confidence interval [CI], 69.5-89.9) (52/64), 98.4% (95% CI, 91.2-100.0) (60/61), and 98.5% (95% CI, 91.7-100.0) (64/65), respectively. The overall SVR rate was 92.3% (95% CI, 83.0-97.5) (60/65). Albumin-bilirubin (ALBI) scores decreased during and after treatment (p < 0.001), and there were significant differences between baseline and end of treatment and between baseline and SVR12. Subgroup analyses showed no significant differences in SVR rates according to patient age, sex, HCV genotype (subtype), Child-Pugh classification, modified ALBI grade, presence of ascites, presence of hepatic coma, or history of hepatocellular carcinoma. In all subpopulations, the SVR rates were higher than 80%. There were no severe adverse events associated with the treatment. The SOF/VEL regimen showed good virological efficacy and acceptable safety even in patients with HCV-related decompensated cirrhosis.
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Affiliation(s)
- Toshifumi Tada
- Department of Internal medicine, Japanese Red Cross Himeji Hospital, Hyogo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Japanese Red Cross Musashino Hospital, Tokyo, Japan
| | - Shinichiro Nakamura
- Department of Internal medicine, Japanese Red Cross Himeji Hospital, Hyogo, Japan
| | - Chitomi Hasebe
- Department of Gastroenterology, Japanese Red Cross Asahikawa Hospital, Hokkaido, Japan
| | - Yuji Kojima
- Department of Hepatology, Japanese Red Cross Ise Hospital, Ise, Mie, Japan
| | - Koichiro Furuta
- Department of Gastroenterology, Japanese Red Cross Masuda Hospital, Shimane, Japan
| | - Haruhiko Kobashi
- Department of Hepatology, Japanese Red Cross Okayama Hospital, Okayama, Japan
| | - Hiroyuki Kimura
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - Chikara Ogawa
- Department of Gastroenterology, Takamatsu Red Cross Hospital, Kagawa, Japan
| | - Hitoshi Yagisawa
- Department of Gastroenterology, Japanese Red Cross Akita Hospital, Akita, Japan
| | - Yasushi Uchida
- Department of Gastroenterology, Japanese Red Cross Matsue Hospital, Shimane, Japan
| | - Kouji Joko
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Takehiro Akahane
- Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Miyagi, Japan
| | - Hirotaka Arai
- Department of Gastroenterology, Japanese Red Cross Maebashi Hospital,, Gunma, Japan
| | - Hiroyuki Marusawa
- Department of Gastroenterology, Japanese Red Cross Osaka Hospital, Osaka, Japan
| | - Ryoichi Narita
- Department of Gastroenterology, Japanese Red Cross Oita Hospital, Oita, Japan
| | - Yasushi Ide
- Department of Gastroenterology, Japanese Red Cross Karatsu Hospital, Saga, Japan
| | - Takashi Sato
- Department of Gastroenterology, Japanese Red Cross Nasu Hospital, Tochigi, Japan
| | - Atsunori Kusakabe
- Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan
| | - Keiji Tsuji
- Department of Gastroenterology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Nami Mori
- Department of Gastroenterology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Masahiko Kondo
- Department of Gastroenterology, Japanese Red Cross Otsu Hospital, Shiga, Japan
| | - Akeri Mitsuda
- Department of Internal Medicine, Japanese Red Cross Tottori Hospital, Tottori, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Japanese Red Cross Musashino Hospital, Tokyo, Japan
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14
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Kang YW, Baek YH, Lee SW, Park SJ, Yoon JS, Yoon KT, Hong Y, Heo NY, Seo KI, Lee SS, Cho HC, Shin JW. Real-world Effectiveness and Safety of Direct-acting Antiviral Agents in Patients with Chronic Hepatitis C Genotype 2 Infection: Korean Multicenter Study. J Korean Med Sci 2021; 36:e142. [PMID: 34060258 PMCID: PMC8167412 DOI: 10.3346/jkms.2021.36.e142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 04/25/2021] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND The advancement of treatment with direct-acting antiviral (DAA) agents has improved the cure rate of hepatitis C virus (HCV) infection close to 100%. The aim of our study was to assess the real-world effectiveness and safety of DAA regimens for the treatment of patients with chronic HCV genotype 2. METHODS We retrospectively analyzed the clinical data of patients treated with sofosbuvir plus ribavirin (SOF + RBV) or glecaprevir/pibrentasvir (G/P) for chronic HCV genotype 2 infection at seven university hospitals in the Korean southeast region. RESULTS SOF + RBV therapy produced an 89% and 98.3% sustained virologic response 12 week (SVR12) after treatment completion in the full analysis set and per-protocol set, respectively, and the corresponding values for G/P therapy were 89.5% and 99.2%, respectively. The difference between the treatments was probably because 6.2% (59/953) of patients in the SOF + RBV group did not complete the treatment and 9.8% (14/143) in the G/P group did not test HCV RNA after treatment completion. Adverse events (A/Es) were reported in 59.7% (569/953) and 25.9% (37/143) of the SOF + RBV and G/P groups, respectively. In the SOF + RBV group, 12 (1.26%) patients discontinued treatment owing to A/Es, whereas no patients discontinued treatment because of A/Es in the G/P group. CONCLUSION In both treatment groups, SVR was high when treatment was completed. However, there was a high dropout rate in the SOF + RBV group, and the dropout analysis showed that these were patients with liver cirrhosis (LC; 43/285, 15.1%), especially those with decompensated LC (12/32, 37.5%). Therefore, an early initiation of antiviral therapy is recommended for a successful outcome before liver function declines. Furthermore, patients with decompensated LC who are considered candidates for SOF + RBV treatment should be carefully monitored to ensure that their treatment is completed, especially those with low hemoglobin and high alanine transaminase.
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Affiliation(s)
- Yeo Wool Kang
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
| | - Yang Hyun Baek
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea.
| | - Sung Wook Lee
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
| | - Sung Jae Park
- Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Korea
| | - Jun Sik Yoon
- Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Youngmi Hong
- Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Nae Yun Heo
- Department of Internal Medicine, Inje University Haeundae Paik Hospital, Busan, Korea
| | - Kwang Il Seo
- Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Korea
| | - Sang Soo Lee
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea
| | - Hyun Chin Cho
- Department of Internal Medicine, College of Medicine, Gyeongsang National University, Jinju, Korea
| | - Jung Woo Shin
- Department of Internal Medicine, Ulsan University College of Medicine, Ulsan, Korea
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15
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Tamaki N, Kurosaki M, Yasui Y, Mori N, Tsuji K, Hasebe C, Joko K, Akahane T, Furuta K, Kobashi H, Kimura H, Yagisawa H, Marusawa H, Kondo M, Kojima Y, Yoshida H, Uchida Y, Loomba R, Izumi N. Change in Fibrosis 4 Index as Predictor of High Risk of Incident Hepatocellular Carcinoma After Eradication of Hepatitis C Virus. Clin Infect Dis 2021; 73:e3349-e3354. [PMID: 33544129 DOI: 10.1093/cid/ciaa1307] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND It is unclear whether the fibrosis 4 index (FIB-4), a marker of liver fibrosis, at baseline and change in FIB-4 after sustained virological response (SVR) is associated with incident hepatocellular carcinoma (HCC) risk. In this study, we examined the association of incident HCC risk with baseline FIB-4 and sustained high FIB-4 (>3.25) at any time point after SVR. METHODS A total of 3823 patients who received direct-acting antiviral treatment and achieved SVR were enrolled. The FIB-4 was measured 24 weeks after the end of direct-acting antiviral treatment and achievement of SVR (SVR24), and 1, 2, and 3 years after SVR24, after which subsequent HCC development was investigated. RESULTS In patients with an FIB-4 >3.25 at SVR24 and 1, 2, and 3 years after SVR24, subsequent HCC development was significantly higher than in those with an FIB-4 ≤3.25 at each point. The rates of HCC development 1, 2, 3, and 4 years after SVR24 were significantly higher in patients with sustained FIB-4 >3.25 than in those whose FIB-4 decreased to ≤3.25 (5.4%, 9.2%, 11.7%, and 16.0%, respectively, vs 2.2%, 3.1%, 3.7%, and 4.4%; P < .001). The adjusted hazard ratios (95% confidence intervals) for an FIB-4 >3.25 at SVR24 and 1, 2, and 3 years later were 3.38 (2.4-4.8), 2.95 (1.9-4.7), 2.62 (1.3-5.1), and 3.37 (1.4-9.8), respectively. CONCLUSIONS The FIB-4 could be used to assess HCC development risk at any time after SVR, and changes in FIB-4 were associated with changes in the HCC development risk. Repeated assessments of FIB-4 could serve as a prognostic indicator of a high-risk HCC cohort that may require more intensive HCC surveillance strategy.
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Affiliation(s)
- Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.,NAFLD Research Center, Division of Medicine, University of California San Diego, La Jolla, California, USA
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yutaka Yasui
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Nami Mori
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Keiji Tsuji
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Chitomi Hasebe
- Department of Gastroenterology, Japanese Red Cross Asahikawa Hospital, Asahikawa, Japan
| | - Koji Joko
- Center for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Matsuyama, Japan
| | - Takehiro Akahane
- Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Japan
| | - Koichiro Furuta
- Department of Gastroenterology, Masuda Red Cross Hospital, Masuda, Japan
| | - Haruhiko Kobashi
- Department of Gastroenterology, Japanese Red Cross Okayama Hospital, Okayama, Japan
| | - Hiroyuki Kimura
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - Hitoshi Yagisawa
- Department of Gastroenterology, Japanese Red Cross Akita Hospital, Akita, Japan
| | - Hiroyuki Marusawa
- Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan
| | - Masahiko Kondo
- Department of Gastroenterology, Japanese Red Cross Otsu Hospital, Otsu, Japan
| | - Yuji Kojima
- Department of Hepatology, Japanese Red Cross Ise Hospital, Ise, Japan
| | - Hideo Yoshida
- Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Yasushi Uchida
- Department of Gastroenterology, Matsue Red Cross Hospital, Matsue, Japan
| | - Rohit Loomba
- NAFLD Research Center, Division of Medicine, University of California San Diego, La Jolla, California, USA
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
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16
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Nakajima T, Karino Y, Hige S, Suii H, Tatsumi R, Yamaguchi M, Arakawa T, Kuwata Y, Hasegawa T, Toyota J. Factors affecting the recovery of hepatic reserve after sustained virologic response by direct-acting antiviral agents in chronic hepatitis C virus-infected patients. J Gastroenterol Hepatol 2021; 36:367-375. [PMID: 32991760 DOI: 10.1111/jgh.15280] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 09/12/2020] [Accepted: 09/21/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Since the advent of direct-acting antiviral (DAA) therapy, the total eradication of hepatitis C virus has been achievable with the recovery of hepatic reserve after achievement of sustained virologic response (SVR). Hence, here, we examined the factors affecting the recovery of hepatic reserve. METHODS We followed up 403 patients (male: 164, female: 239; genotype 1: 299, genotype 2: 104; median age: 69 years) for at least 3 years after they achieved SVR to DAA therapy. Of these patients, 75 (18.6%) had a history of hepatocellular carcinoma (HCC). Biochemical tests were periodically performed, and the hepatic reserve was evaluated based on the albumin-bilirubin grade. We examined background factors such as age, biochemical test results, HCC occurrence and portosystemic shunt by computed tomography. RESULTS At the start of treatment, the albumin-bilirubin grades were grades 1, 2, and 3 in 241, 157, and 5 patients, respectively, and 3 years later, 117 of 162 (72%) patients with grade 2 or 3 improved to grade 1. Multivariate analysis identified the HCC occurrence after achievement of SVR (hazard ratio [HR]: 3.08, P < 0.0138), male sex (HR: 3.45, P = 0.0143), hemoglobin level of <11.5 g/dL (HR: 4.19, P = 0.0157), the presence of a portosystemic shunt (HR: 3.07, P = 0.0349), and alanine aminotransferase levels <45 U/L (HR: 2.67, P = 0.0425) as factors inhibiting improvement to grade 1. However, old age was not an inhibitory factor. CONCLUSION Our results demonstrate that hepatic reserve could be improved even in elderly patients over a long course of time.
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Affiliation(s)
- Tomoaki Nakajima
- Department of Hepatology, Sapporo-Kosei General Hospital, Sapporo, Japan
| | - Yoshiyasu Karino
- Department of Hepatology, Sapporo-Kosei General Hospital, Sapporo, Japan.,Department of Gastroenterology, Keiyukai Sapporo Hospital, Sapporo, Japan
| | - Shuhei Hige
- Department of Hepatology, Sapporo-Kosei General Hospital, Sapporo, Japan
| | - Hirokazu Suii
- Department of Hepatology, Sapporo-Kosei General Hospital, Sapporo, Japan
| | - Ryoji Tatsumi
- Department of Hepatology, Sapporo-Kosei General Hospital, Sapporo, Japan
| | | | - Tomohiro Arakawa
- Department of Hepatology, Sapporo-Kosei General Hospital, Sapporo, Japan
| | - Ysuaki Kuwata
- Department of Hepatology, Sapporo-Kosei General Hospital, Sapporo, Japan
| | - Takashi Hasegawa
- Department of Radiology, Sapporo-Kosei General Hospital, Sapporo, Japan
| | - Joji Toyota
- Department of Hepatology, Sapporo-Kosei General Hospital, Sapporo, Japan
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17
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Jang ES, Kim KA, Kim YS, Kim IH, Lee BS, Lee YJ, Chung WJ, Jeong SH. Real-Life Effectiveness and Safety of Sofosbuvir-Based Therapy in Genotype 2 Chronic Hepatitis C Patients in South Korea, with Emphasis on the Ribavirin Dose. Gut Liver 2020; 14:775-782. [PMID: 32000468 PMCID: PMC7667937 DOI: 10.5009/gnl19260] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Revised: 09/18/2019] [Accepted: 10/26/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND/AIMS Sofosbuvir (SOF)-based therapy has been used in Korean patients with chronic hepatitis C virus (HCV) infection since January 2016. This study aimed to investigate the real-life effectiveness and safety of SOF-based therapy in genotype 2 HCV infection. METHODS From January to December 2016, 458 genotype 2 HCV-infected patients who received ≥1 dose of SOF-based therapy were consecutively enrolled in seven tertiary hospitals. Sustained virologic response (SVR) rates and safety were determined by intention- to-treat (ITT) and per-protocol (PP) analyses. RESULTS The mean age of the patients was 61.0 years; 183 (40%) were male, and 13.1% showed a high viral load (>6,000,000 IU/ mL). Among the 378 treatment-naïve patients, the SVR rates were 94.2% (ITT) and 96.7% (PP). Among the 80 treatmentexperienced patients, the SVR rates were 96.3% (ITT) and 98.7% (PP). Patients with a relatively high fibrosis-4 index score (>3.25) had similar SVR rates to those with a relatively low score (p=0.756). A total of 314 patients (68.6%) were treated with a reduced ribavirin dose at the prescriber's discretion, but they showed similar SVR rates to those treated with the weight-based dose (ITT: 95.5% and 92.3%, PP: 97.4% and 96.3%, respectively). Adverse events were observed in 191 patients (41.7%), including 86 (18.8%) with anemia, but only one (0.2%) discontinued antiviral therapy due to nausea. CONCLUSIONS SOF-based therapy showed high real-life efficacy and tolerability in Korean patients with genotype 2 chronic HCV infection, regardless of previous antiviral treatment experience and fibrosis score. A reduced ribavirin dose can be considered in this patient cohort.
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Affiliation(s)
- Eun Sun Jang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Kyung-Ah Kim
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea
| | - Young Seok Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - In Hee Kim
- Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea
| | - Byung Seok Lee
- Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea
| | - Youn Jae Lee
- Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Woo Jin Chung
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Sook-Hyang Jeong
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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18
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Cheng TS, Liang PC, Huang CF, Yeh ML, Huang CI, Lin ZY, Chen SC, Huang JF, Dai CY, Hsieh PH, Chuang WL, Yu ML. Real-world effectiveness of direct-acting antiviral agents for chronic hepatitis C patients with genotype-2 infection after completed treatment. Kaohsiung J Med Sci 2020; 37:334-345. [PMID: 33151016 DOI: 10.1002/kjm2.12315] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 09/12/2020] [Accepted: 09/23/2020] [Indexed: 12/12/2022] Open
Abstract
Chronic hepatitis C (CHC) is a major cause of cirrhosis, hepatocellular carcinoma (HCC), and mortality. Eliminating hepatitis C virus (HCV) can greatly improve long-term outcomes. Several direct-acting antiviral agents (DAAs), including sofosbuvir (SOF) plus different NS5A inhibitors, as well as non-SOF-based DAAs, including glecaprevir/pibrentasvir (GLE/PIB), have been approved for treating CHC genotype-2 (GT-2) patients in Taiwan. However, there is limited real-world effectiveness data regarding these different regimens. Thus, we aimed to evaluate the real-world efficacy in CHC GT-2 patients who underwent these DAA regimens. We retrospectively enrolled CHC GT-2 patients who were treated with SOF-based DAAs or GLE/PIB at a single medical center. A total of 704 enrolled patients were treated with either SOF + ribavirin (RBV), SOF/daclatasvir (DCV) ± RBV, SOF/ledipasvir (LDV) ± RBV, SOF/velpatasvir (VEL) ± RBV, or with GLE/PIB. The overall sustained virological response (SVR) rate was 97.9%. The SVR rate was significantly lower in the SOF + RBV group (95.6%) than in the non-SOF + RBV (98.9%) group, especially compared to the SOF/DCV (100%) and GLE/PIB groups (99.5%). Among patients treated with SOF + RBV, cirrhotic patients had significantly lower SVR rates than noncirrhotic patients (89.4% vs 98.2%). Multivariate analysis showed that patients with a younger age, hepatitis B virus coinfection, baseline cirrhosis, or those who received SOF + RBV were less likely to achieve SVR. In conclusion, for CHC GT-2 patients, SOF in combination with DCV, LDV, or VEL, as well as GLE/PIB, achieved similar high efficacies, regardless of cirrhosis, treatment experience, or chronic kidney disease status. Therefore, the use of DAA therapy to eradicate HCV should not be delayed in these populations.
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Affiliation(s)
- Tzu-Sheng Cheng
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.,Department of Chemistry, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Ping-Hsin Hsieh
- Department of Internal Medicine, Chi Mei Hospital, Liouying, Tainan, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan
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19
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Tamai H, Shingaki N, Ida Y, Shimizu R, Maeshima S, Okamura J, Kawashima A, Nakao T, Hara T, Matsutani H, Nishikawa I, Higashi K. Sofosbuvir plus ribavirin is tolerable and effective even in elderly patients 75-years-old and over. World J Hepatol 2020; 12:672-684. [PMID: 33033572 PMCID: PMC7522558 DOI: 10.4254/wjh.v12.i9.672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 07/12/2020] [Accepted: 07/26/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Although clinical use of sofosbuvir plus ribavirin has been approved for patients infected with genotype 2 hepatitis C virus, patients ≥ 75-years-old have not been included in previous clinical trials.
AIM To evaluate the real-world safety and efficacy of sofosbuvir plus ribavirin for elderly patients (≥ 75-years-old) compared to nonelderly patients, we conducted a post-marketing prospective cohort study.
METHODS We treated 265 patients with genotype 2 hepatitis C virus using standard approved doses of sofosbuvir (400 mg/d) plus ribavirin adjusted by body weight, administered orally for 12 wk.
RESULTS Sustained virological response rates for the overall cohort, patients < 65-years-old, ≥ 65-years-old but < 75-years-old, and ≥ 75-years-old were 97% (258/265), 98% (93/95), 97% (84/87), and 98% (81/83), respectively (P = 0.842). Logistic regression analyses identified history of hepatocellular carcinoma treatment and alpha-fetoprotein as factors significantly associated with sustained virological response. Alpha-fetoprotein was the only independent factor identified. Sustained virological response rate was significantly lower for patients with hepatocellular carcinoma treatment (91%) than for patients without history of hepatocellular carcinoma treatment (98%, P = 0.004). One patient (0.4%) discontinued treatment due to drug-induced pneumonia. Dose reduction or interruption of ribavirin was required for 12.1% (32/265) of patients because of anemia, including 7.7% (14/182) of patients < 75-years-old and 21.7% (18/83) of patients ≥ 75-years-old (P = 0.002).
CONCLUSION Although ribavirin dose reduction or interruption was required with advanced age, sofosbuvir plus ribavirin appears tolerable and highly effective even in patients ≥ 75-years-old.
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Affiliation(s)
- Hideyuki Tamai
- Department of Hepatology, Wakayama Rosai Hospital, Wakayama 6408505, Japan
| | - Naoki Shingaki
- Department of Hepatology, Wakayama Rosai Hospital, Wakayama 6408505, Japan
| | - Yoshiyuki Ida
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama 6418509, Japan
| | - Ryo Shimizu
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama 6418509, Japan
| | - Shuya Maeshima
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama 6418509, Japan
| | - Junpei Okamura
- Department of Internal Medicine, Naga Municipal Hospital, Wakayama 6496414, Japan
| | - Akira Kawashima
- Department of Internal Medicine, Naga Municipal Hospital, Wakayama 6496414, Japan
| | - Taisei Nakao
- Department of Internal Medicine, Naga Municipal Hospital, Wakayama 6496414, Japan
| | - Takeshi Hara
- Department of Gastroenterology, Wakayama Rosai Hospital, Wakayama 6408505, Japan
| | - Hiroyoshi Matsutani
- First Department of Internal Medicine, Hidaka General Hospital, Wakayama 6440002, Japan
| | - Izumi Nishikawa
- First Department of Internal Medicine, Hidaka General Hospital, Wakayama 6440002, Japan
| | - Katsuhiko Higashi
- First Department of Internal Medicine, Hidaka General Hospital, Wakayama 6440002, Japan
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20
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Tamaki N, Kurosaki M, Loomba R, Izumi N. Clinical Utility of Mac-2 Binding Protein Glycosylation Isomer in Chronic Liver Diseases. Ann Lab Med 2020; 41:16-24. [PMID: 32829576 PMCID: PMC7443525 DOI: 10.3343/alm.2021.41.1.16] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 06/15/2020] [Accepted: 07/29/2020] [Indexed: 12/15/2022] Open
Abstract
An accurate evaluation of liver fibrosis is clinically important in chronic liver diseases. Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel serum marker for liver fibrosis. In this review, we discuss the role of M2BPGi in diagnosing liver fibrosis in chronic hepatitis B and C, chronic hepatitis C after sustained virologic response (SVR), and nonalcoholic fatty liver disease (NAFLD). M2BPGi predicts not only liver fibrosis but also the hepatocellular carcinoma (HCC) development and prognosis in patients with chronic hepatitis B and C, chronic hepatitis C after SVR, NAFLD, and other chronic liver diseases. M2BPGi can also be used to evaluate liver function and prognosis in patients with cirrhosis. M2BPGi levels vary depending on the etiology and the presence or absence of treatment. Therefore, the threshold of M2BPGi for diagnosing liver fibrosis and predicting HCC development has to be adjusted according to the background and treatment status.
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Affiliation(s)
- Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.,NAFLD Research Center, Division of Medicine, University of California, San Diego, La Jolla, California, USA
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Rohit Loomba
- NAFLD Research Center, Division of Medicine, University of California, San Diego, La Jolla, California, USA
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
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21
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Saleh SA, Salama MM, Alhusseini MM, Mohamed GA. M2BPGi for assessing liver fibrosis in patients with hepatitis C treated with direct-acting antivirals. World J Gastroenterol 2020; 26:2864-2876. [PMID: 32550761 PMCID: PMC7284180 DOI: 10.3748/wjg.v26.i21.2864] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2020] [Revised: 03/27/2020] [Accepted: 05/28/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Assessing liver fibrosis is important for predicting the efficacy of direct-acting antivirals (DAAs) and patient prognosis. Non-invasive techniques to assess liver fibrosis are becoming important. Recently, serum Mac-2 binding protein glycosylation isomer (M2BPGi) was identified as a non-invasive marker of liver fibrosis.
AIM To investigate the diagnostic accuracy of M2BPGi in assessing liver fibrosis in patients with chronic hepatitis C (CHC) treated with DAAs.
METHODS From December 2017 to August 2018, 80 treatment-naïve adult patients with CHC who were eligible for DAAs therapy were consecutively enrolled in this observational cohort study. For 12 weeks, 65 patients were treated with sofosbuvir/daclatasvir, and 15 patients were treated with sofosbuvir/daclatasvir and a weight-based dose of ribavirin at knowledge and technology association for hepatitis C management clinic, Cairo, Egypt. We measured serum M2BPGi levels, PAPAS index, fibrosis-4 (FIB-4) score and liver stiffness measurements (LSM) at baseline and 12 weeks after the end of treatment. Serum M2BPGi levels were measured using enzyme-linked immunosorbent assay.
RESULTS All patients achieved sustained virologic response (SVR12) (100%). Serum M2BPGi levels, LSM, FIB-4 score and PAPAS index decreased significantly at SVR12 (P < 0.05). Serum M2BPGi levels correlated positively with LSM at baseline and SVR12 (P < 0.001). At baseline, compared with the FIB-4 score and PAPAS index, M2BPGi was the best marker to distinguish patients with grade F4 fibrosis (AUC = 0.801, P < 0.001), patients with grade F2 from grade F0-1 fibrosis (AUC = 0.713, P = 0.012), patients with grade F3-4 from grade F0-2 fibrosis (AUC = 0.730, P < 0.001), and patients with grade F2-4 from grade F0-1 fibrosis (AUC = 0.763, P < 0.001). At SVR12, M2BPGi had the greatest AUCs for differentiating patients with grade F4 fibrosis (AUC = 0.844, P < 0.001), patients with grade F3 from grade F0-2 fibrosis (AUC = 0.893, P = 0.002), patients with grade F3-4 from grade F0-2 fibrosis (AUC = 0.891, P < 0.001), and patients with grade F2-4 from grade F0-1 fibrosis (AUC = 0.750, P < 0.001).
CONCLUSION M2BPGi is a reliable marker for the non-invasive assessment and prediction of liver fibrosis regression in patients with CHC who achieved an SVR with DAAs therapy.
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Affiliation(s)
- Shereen A Saleh
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11341, Egypt
| | - Mohamed M Salama
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11341, Egypt
| | - Marwan M Alhusseini
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11341, Egypt
| | - Ghada A Mohamed
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11341, Egypt
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22
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Osawa L, Tamaki N, Kurosaki M, Kirino S, Watakabe K, Wang W, Okada M, Shimizu T, Higuchi M, Takaura K, Takada H, Kaneko S, Yasui Y, Tsuchiya K, Nakanishi H, Itakura J, Takahashi Y, Enomoto N, Izumi N. Wisteria floribunda Agglutinin-Positive Mac-2 Binding Protein but not α-fetoprotein as a Long-Term Hepatocellular Carcinoma Predictor. Int J Mol Sci 2020; 21:E3640. [PMID: 32455631 PMCID: PMC7279305 DOI: 10.3390/ijms21103640] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 05/18/2020] [Accepted: 05/19/2020] [Indexed: 02/06/2023] Open
Abstract
Identification of high-risk patients for hepatocellular carcinoma (HCC) after sustained virological responses (SVR) is necessary to define candidates for long-term surveillance. In this study, we examined whether serum markers after 1 year of SVR could predict subsequent HCC development. Total 734 chronic hepatitis C patients without a history of HCC who achieved SVR with direct-acting antivirals were included. The regular surveillance for HCC started from 24 weeks after the end of treatment (SVR24). Factors at SVR24 and 1 year after SVR24 were analyzed for predicting HCC development. During the mean observation period of 19.7 ± 10 months, 24 patients developed HCC. At SVR24, Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA±M2BP) ≥ 1.85 and α-fetoprotein (AFP) ≥ 6.0 ng/mL were independent factors of HCC development. However, at 1 year after SVR24, WFA±M2BP ≥ 1.85 was associated with subsequent HCC development (hazard ratio: 23.5, 95% confidence interval: 2.68-205) but not AFP. Among patients with WFA±M2BP ≥ 1.85 at SVR24, 42% had WFA±M2BP < 1.85 at 1 year after SVR24 (WFA±M2BP declined group). Subsequent HCC development was significantly lower in the declined group than in the non-declined group (1 year HCC rate: 0% vs. 9.4%, p = 0.04). In conclusion, WFA±M2BP but not AFP could identify high and no-risk cases of HCC at 1 year after SVR. Therefore, it was useful as a real-time monitoring tool to identify the candidates for continuous surveillance for HCC.
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Affiliation(s)
- Leona Osawa
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (L.O.); (N.T.); (M.K.); (S.K.); (K.W.); (W.W.); (M.O.); (T.S.); (M.H.); (K.T.); (H.T.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.); (Y.T.)
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan;
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (L.O.); (N.T.); (M.K.); (S.K.); (K.W.); (W.W.); (M.O.); (T.S.); (M.H.); (K.T.); (H.T.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.); (Y.T.)
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan;
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (L.O.); (N.T.); (M.K.); (S.K.); (K.W.); (W.W.); (M.O.); (T.S.); (M.H.); (K.T.); (H.T.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.); (Y.T.)
| | - Sakura Kirino
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (L.O.); (N.T.); (M.K.); (S.K.); (K.W.); (W.W.); (M.O.); (T.S.); (M.H.); (K.T.); (H.T.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.); (Y.T.)
| | - Keiya Watakabe
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (L.O.); (N.T.); (M.K.); (S.K.); (K.W.); (W.W.); (M.O.); (T.S.); (M.H.); (K.T.); (H.T.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.); (Y.T.)
| | - Wan Wang
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (L.O.); (N.T.); (M.K.); (S.K.); (K.W.); (W.W.); (M.O.); (T.S.); (M.H.); (K.T.); (H.T.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.); (Y.T.)
| | - Mao Okada
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (L.O.); (N.T.); (M.K.); (S.K.); (K.W.); (W.W.); (M.O.); (T.S.); (M.H.); (K.T.); (H.T.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.); (Y.T.)
| | - Takao Shimizu
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (L.O.); (N.T.); (M.K.); (S.K.); (K.W.); (W.W.); (M.O.); (T.S.); (M.H.); (K.T.); (H.T.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.); (Y.T.)
| | - Mayu Higuchi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (L.O.); (N.T.); (M.K.); (S.K.); (K.W.); (W.W.); (M.O.); (T.S.); (M.H.); (K.T.); (H.T.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.); (Y.T.)
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan;
| | - Kenta Takaura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (L.O.); (N.T.); (M.K.); (S.K.); (K.W.); (W.W.); (M.O.); (T.S.); (M.H.); (K.T.); (H.T.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.); (Y.T.)
| | - Hitomi Takada
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (L.O.); (N.T.); (M.K.); (S.K.); (K.W.); (W.W.); (M.O.); (T.S.); (M.H.); (K.T.); (H.T.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.); (Y.T.)
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan;
| | - Shun Kaneko
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (L.O.); (N.T.); (M.K.); (S.K.); (K.W.); (W.W.); (M.O.); (T.S.); (M.H.); (K.T.); (H.T.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.); (Y.T.)
| | - Yutaka Yasui
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (L.O.); (N.T.); (M.K.); (S.K.); (K.W.); (W.W.); (M.O.); (T.S.); (M.H.); (K.T.); (H.T.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.); (Y.T.)
| | - Kaoru Tsuchiya
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (L.O.); (N.T.); (M.K.); (S.K.); (K.W.); (W.W.); (M.O.); (T.S.); (M.H.); (K.T.); (H.T.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.); (Y.T.)
| | - Hiroyuki Nakanishi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (L.O.); (N.T.); (M.K.); (S.K.); (K.W.); (W.W.); (M.O.); (T.S.); (M.H.); (K.T.); (H.T.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.); (Y.T.)
| | - Jun Itakura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (L.O.); (N.T.); (M.K.); (S.K.); (K.W.); (W.W.); (M.O.); (T.S.); (M.H.); (K.T.); (H.T.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.); (Y.T.)
| | - Yuka Takahashi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (L.O.); (N.T.); (M.K.); (S.K.); (K.W.); (W.W.); (M.O.); (T.S.); (M.H.); (K.T.); (H.T.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.); (Y.T.)
| | - Nobuyuki Enomoto
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan;
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan; (L.O.); (N.T.); (M.K.); (S.K.); (K.W.); (W.W.); (M.O.); (T.S.); (M.H.); (K.T.); (H.T.); (S.K.); (Y.Y.); (K.T.); (H.N.); (J.I.); (Y.T.)
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23
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Ogawa E, Nomura H, Nakamuta M, Kawano A, Dohmen K, Kajiwara E, Satoh T, Koyanagi T, Takahashi K, Ooho A, Azuma K, Furusyo N, Kato M, Shimoda S, Hayashi J. Ledipasvir and sofosbuvir for 12 weeks for hepatitis C virus genotype 2 infection: A propensity score matched analysis. Hepatol Res 2020; 50:174-181. [PMID: 31634412 DOI: 10.1111/hepr.13437] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 09/16/2019] [Accepted: 10/01/2019] [Indexed: 12/11/2022]
Abstract
AIM Hepatitis C virus genotype 2 is common in East Asia, sub-Saharan Africa, and Latin America. However, many countries in these areas lag behind other areas of the world in government approval for new direct-acting antivirals. The aim of this study was to evaluate the treatment outcome of ledipasvir/sofosbuvir (LDV/SOF) for patients with chronic hepatitis C virus genotype 2 infection. METHODS This is a two-part multicenter, real-world cohort study. Study 1 consisted of 58 consecutive patients who were treated with LDV/SOF for 12 weeks. Study 2 used propensity score matching for LDV/SOF (n = 58) and glecaprevir/pibrentasvir (n = 207) treatment groups (1:1) with a set of clinically important variables. Sustained viral response 12 weeks after the end of treatment (SVR12) and adverse events were evaluated in both studies. RESULTS In study 1, the overall SVR12 rates of the intention-to-treat and modified intention-to-treat populations were 94.8% (55/58) and 96.5% (55/57), respectively. High SVR12 rates were observed in almost all subgroups, including older age, compensated cirrhosis, and treatment experience. In study 2, propensity score matching of the entire study population yielded 52 matched pairs with similar baseline characteristics. There were no statistically significant differences between the LDV/SOF (96.1%) and glecaprevir/pibrentasvir (98.0%) groups in the overall SVR12 rates of the modified intention-to-treat populations, and their rates of treatment discontinuation and adverse events were similar. CONCLUSIONS Treatment with LDV/SOF for hepatitis C virus genotype 2 resulted in a high rate of SVR12 and excellent tolerability. The outcomes of LDV/SOF were very similar to those of glecaprevir/pibrentasvir.
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Affiliation(s)
- Eiichi Ogawa
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Hideyuki Nomura
- The Center for Liver Disease, Shin-Kokura Hospital, Kitakyushu, Japan.,Department of Medicine, Haradoi Hospital, Fukuoka, Japan
| | - Makoto Nakamuta
- Department of Gastroenterology, Kyushu Medical Center, National Hospital Organization, Fukuoka, Japan
| | - Akira Kawano
- Department of Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan
| | - Kazufumi Dohmen
- Department of Internal Medicine, Chihaya Hospital, Fukuoka, Japan
| | | | - Takeaki Satoh
- Center for Liver Disease, Kokura Medical Center, Kitakyushu, Japan
| | | | | | - Aritsune Ooho
- Department of Hepatology, Steel Memorial Yawata Hospital, Kitakyushu, Japan
| | - Koichi Azuma
- Department of Medicine, Kyushu Central Hospital, Fukuoka, Japan
| | - Norihiro Furusyo
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Masaki Kato
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shinji Shimoda
- Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Jun Hayashi
- Kyushu General Internal Medicine Center, Haradoi Hospital, Fukuoka, Japan
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24
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Tsai WL, Wang CF, Cheng JS, Chen WC, Bair MJ, Lo CC. Sofosbuvir-based regimen for genotype 2 HCV infected patients in Taiwan: A real world experience. PLoS One 2020; 15:e0227424. [PMID: 31923251 PMCID: PMC6953822 DOI: 10.1371/journal.pone.0227424] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Accepted: 12/18/2019] [Indexed: 12/18/2022] Open
Abstract
Background Sofosbuvir (SOF)-based regimens achieve excellent efficacy and safety in the treatment of chronic hepatitis C (CHC) with various genotypes. There are few real-world instances of the use of SOF-based regimens to treat genotype 2 CHC. This study determines the effectiveness and safety of SOF/Ribavirn (RBV), SOF/Daclatasvir (DCV) and SOF/DCV/RBV in the treatment of genotype 2 CHC patients in Taiwan. Material and methods Patients with genotype 2 CHC were treated for 12 weeks with SOF/RBV, SOF/DCV or SOF/DCV/RBV under the National Health Insurance reimbursement program in three hospitals in Taiwan. The sustained virological response at 12 weeks (SVR12) was determined. Adverse events were recorded for a safety analysis. Results A total of 467 genotype 2 CHC patients were enrolled from January to October 2018. One hundred and eleven patients (24%) had cirrhosis, including 10 patients (2.1%) with hepatic decompensation. Fifty-five patients (12%) had already experienced interferon-alpha/RBV treatment. Forty-two patients (9%) had a history of hepatocellular carcinoma (HCC) in the baseline. Three hundred and fifty-five patients received SOF/RBV, forty-seven patients received SOF/DCV and sixty-two patients received SOF/DCV/RBV. The SOF/DCV group featured a greater HCV viral load than the SOF/RBV or SOF/DCV/RBV groups. SVR12 was achieved in 94.6% of the SOF/RBV group, 95.7% of the SOF/DCV group and 96.8% of then SOF/DCV/RBV group (P = NS). Thirteen out of 352 patients (3.7%) in the SOF/RBV group, 1 out of 62 patients (1.6%) in the SOF/DCV/RBV group and 1 out of 47 patients (2.1%) in the SOF/DCV group developed virological failure. There are no differences in virological failure between the three groups (P = NS). Multi-variate analysis shows that history of HCC is an independent factor that is associated with the failure of treatment in the SOF/RBV group (odds ratio:4.905, 95% confidence interval (CI): 1.321–18.205, P = 0.017). Hemoglobin levels at 12 weeks are significantly lower in the SOF/RBV and the SOF/RBV/DCV group than in the SOF/DCV group (P<0.05). Serious adverse events (SAE) occurred in six patients (1.6%) in the SOF/RBV group and in one patient (1.6%) in the SOF/RBV/DCV group. No patients in the SOF/DCV group experienced SAE. Conclusions SOF/RBV, SOF/DCV or SOF/DCV/RBV for 12 weeks all achieve very high SVR rates and are equally effective in the treatment of genotype 2 CHC patients in the real world in Taiwan. Patients in the SOF/RBV group who have a history of HCC exhibit a lower SVR rate.
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Affiliation(s)
- Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chih-Feng Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Jin-Shiung Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Wen-Chi Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Mackay Medical College, New Taipei City, Taiwan
- * E-mail: (CCL); (MJB)
| | - Ching-Chu Lo
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan
- Chung-Jen junior College of Nursing, Health Sciences and Management, Chiayi, Taiwan
- * E-mail: (CCL); (MJB)
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25
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Kusakabe A, Kurosaki M, Itakura J, Joko K, Akahane T, Tsuji K, Kobashi H, Sohda T, Kimura H, Narita R, Furuta K, Izumi N. Efficacy and safety of glecaprevir/pibrentasvir as retreatment therapy for patients with genotype 2 chronic hepatitis C who failed prior sofosbuvir plus ribavirin regimen. Hepatol Res 2019; 49:1121-1126. [PMID: 31209976 DOI: 10.1111/hepr.13387] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Revised: 05/29/2019] [Accepted: 06/05/2019] [Indexed: 12/17/2022]
Abstract
AIM Rescue therapy for patients with genotype 2 (GT2) chronic hepatitis C who failed prior sofosbuvir (SOF) plus ribavirin (RBV) awaits establishment. This study aims to investigate the efficacy and safety of the fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg) (GLE/PIB) for patients with GT2 chronic hepatitis C. METHODS In this nationwide observational study undertaken by the Japanese Red Cross Liver Study Group, 28 GT2 patients with prior failure of SOF + RBV were retreated with GLE/PIB for 12 weeks. We evaluated the rate of sustained virologic response (SVR) and adverse events. RESULTS After 4 weeks of therapy, serum hepatitis C virus RNA was below the limit of quantification in all patients. The SVR after 4 and 12 weeks of the end of treatment was validated in 100% (28/28) and 100% (28/28), respectively. The adverse events comprised pruritus (eight patients), fatigue (four patients), and appetite loss (four patients), all of which were mild in severity. CONCLUSIONS This study establishes the efficacy of GLE/PIB as retreatment in Japanese patients with GT2 chronic hepatitis C not responding to SOF + RBV.
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Affiliation(s)
- Atsunori Kusakabe
- Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Jun Itakura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kouji Joko
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Matsuyama, Japan
| | - Takehiro Akahane
- Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Japan
| | - Keiji Tsuji
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Haruhiko Kobashi
- Department of Hepatology, Japanese Red Cross Okayama Hospital, Okayama, Japan
| | - Tetsuro Sohda
- Department of Hepatology, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan
| | - Hiroyuki Kimura
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - Ryouichi Narita
- Department of Gastroenterology, Oita Red Cross Hospital, Oita, Japan
| | - Koichirou Furuta
- Department of Gastroenterology, Masuda Red Cross Hospital, Masuda, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
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26
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Chen CC, Tung SY, Wei KL, Shen CH, Chang TS, Chen WM, Xu HW, Yen CW, Chen YH, Lu SN, Hung CH. Incidence, risk factors and impact on virological response of anemia in chronic genotype 2 hepatitis C receiving sofosbuvir plus ribavirin. J Formos Med Assoc 2019; 119:532-537. [PMID: 31445848 DOI: 10.1016/j.jfma.2019.07.028] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 07/14/2019] [Accepted: 07/31/2019] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND/PURPOSE The major dose-limiting toxicity of ribavirin is hemolytic anemia. We investigated the incidence, risk factors and impact on virological response of anemia in chronic hepatitis C genotype 2 patients receiving sofosbuvir plus ribavirin therapy. METHODS This was a retrospective real-world analysis of a single center including 293 chronic hepatitis C genotype 2 patients treated with sofosbuvir plus ribavirin for 12 weeks. Severe anemia was defined as hemoglobin concentration <10 g/dl. RESULTS Treatment was completed in 285 (97%) of patients, of whom one withdrew due to severe anemia. Ribavirin dose reduction was required in 88 (30%) of patients. After excluding those with baseline hemoglobin <10 g/dl, 79 (29%) patients had developed severe anemia during therapy. Stepwise logistic regression analysis identified that chronic kidney disease (odds ratio [OR] = 3.970, p < 0.001), baseline hemoglobin level (OR = 0.475, p < 0.001) and baseline platelet count (OR = 0.992, p = 0.022) were independent factors. The sustained viral response 12 weeks off therapy (SVR12) rate was 93.9% in the per-protocol population. Multivariate analyses showed that history of hepatocellular carcinoma significantly reduced the efficacy of sofosbuvir plus ribavirin therapy (OR = 0.172, p = 0.001). Severe anemia, dose reduction or average dose (mg/kg/day) of ribavirin was not associated with SVR12. CONCLUSION Severe anemia was not uncommon during sofosbuvir plus ribavirin therapy for chronic hepatitis C genotype 2 patients. Careful monitoring of anemia is necessary in patients with chronic kidney disease and low baseline hemoglobin level and platelet count.
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Affiliation(s)
- Chi-Ching Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Shui-Yi Tung
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Kuo-Liang Wei
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Chien-Heng Shen
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Te-Sheng Chang
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Wei-Ming Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Huang-Wei Xu
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Chih-Wei Yen
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Yi-Hsing Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
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Colombo MG, Musabaev EI, Ismailov UY, Zaytsev IA, Nersesov AV, Anastasiy IA, Karpov IA, Golubovska OA, Kaliaskarova KS, AC R, Hadigal S. Consensus on management of hepatitis C virus infection in resource-limited Ukraine and Commonwealth of Independent States regions. World J Gastroenterol 2019; 25:3897-3919. [PMID: 31413526 PMCID: PMC6689802 DOI: 10.3748/wjg.v25.i29.3897] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Revised: 06/04/2019] [Accepted: 06/08/2019] [Indexed: 02/06/2023] Open
Abstract
Globally, 69.6 million individuals were infected with hepatitis C virus (HCV) infection in 2016. Of the six major HCV genotypes (GT), the most predominant one is GT1, worldwide. The prevalence of HCV in Central Asia, which includes most of the Commonwealth of Independent States (CIS), has been estimated to be 5.8% of the total global burden. The predominant genotype in the CIS and Ukraine regions has been reported to be GT1, followed by GT3. Inadequate HCV epidemiological data, multiple socio-economic barriers, and the lack of region-specific guidelines have impeded the optimal management of HCV infection in this region. In this regard, a panel of regional experts in the field of hepatology convened to discuss and provide recommendations on the diagnosis, treatment, and pre-, on-, and posttreatment assessment of chronic HCV infection and to ensure the optimal use of cost-effective antiviral regimens in the region. A comprehensive evaluation of the literature along with expert recommendations for the management of GT1-GT6 HCV infection with the antiviral agents available in the region has been provided in this review. This consensus document will help guide clinical decision-making during the management of HCV infection, further optimizing treatment outcomes in these regions.
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Affiliation(s)
- Massimo Giuseppe Colombo
- Research and Clinical Center, Department of Medicine, Humanitas Hospital, Rozzano 20089, MI, Italy
| | - Erkin Isakovich Musabaev
- Research Institute of Virology, Scientific Research Institute of Virology, Tashkent 100194, Uzbekistan
| | - Umed Yusupovich Ismailov
- Hepatoсenter, Research Institute of Virology, Scientific Research Institute of Virology, Tashkent 100194, Uzbekistan
| | - Igor A Zaytsev
- Department of Therapy, Infectious Diseases and Dermatology, Bogomolets National Medical University, Kyiv 01601, Ukraine
| | - Alexander V Nersesov
- Department of Gastroenterology and Hepatology, National Research Institute of Cardiology and Internal Diseases, Almaty 050000, Kazakhstan
| | | | | | - Olga A Golubovska
- Department Infectious Diseases, Bogomolets National Medical University, Kyiv 01601, Ukraine
| | | | - Ravishankar AC
- Medical Affairs, Mylan Pharmaceuticals Private Limited, Kadubeesanahalli, Bengaluru 560103, India
| | - Sanjay Hadigal
- Medical Affairs, Mylan Pharmaceuticals Private Limited, Kadubeesanahalli, Bengaluru 560103, India
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Urabe A, Sakamori R, Tahata Y, Yamada R, Imai Y, Hagiwara H, Tamura S, Fukui H, Yamada Y, Kaneko A, Hijioka T, Kodama T, Hikita H, Tatsumi T, Takehara T. Predictive factors of anemia during sofosbuvir and ribavirin therapy for genotype 2 chronic hepatitis C patients. Hepatol Res 2019; 49:853-859. [PMID: 31009550 DOI: 10.1111/hepr.13354] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Revised: 03/05/2019] [Accepted: 04/07/2019] [Indexed: 02/08/2023]
Abstract
AIM Sofosbuvir (SOF) and ribavirin (RBV) combination therapy has improved the sustained virologic response (SVR) rate and shortened the treatment duration for patients with chronic hepatitis C virus (HCV) genotype 2 infection. Ribavirin-induced hemolytic anemia is one of the most troublesome side-effects of SOF/RBV therapy; however, factors associated with this condition have not been fully elucidated. We aimed to identify a safer way to complete treatment with SOF/RBV therapy by examining factors related to RBV-induced hemolytic anemia and identifying patients who did not develop anemia. METHODS Two hundred and one patients with genotype 2 chronic hepatitis C treated with SOF/RBV therapy were studied. Significant factors associated with the decline in hemoglobin (Hb) levels from the baseline were analyzed. RESULTS The SVR rate was 96.5% (194 out of 201 patients) based on intent-to-treat analysis. In multivariate analysis, inosine triphosphatase (ITPA) gene variation (P < 0.0001) and estimated glomerular filtration rate (eGFR) (0.001) were significantly associated with a decrease in Hb levels less than 2 g/dL. All patients were divided into four groups by ITPA and eGFR at baseline, and we identified patients with ITPA CA/AA and eGFR >75 as a group that did not develop anemia. CONCLUSIONS The results presented here suggest that patients with ITPA CA/AA and eGFR >75 had no reduction in Hb levels during the treatment with SOF/RBV in HCV genotype 2-infected patients. Adding RBV to direct-acting antiviral therapy might not be problematic in certain patients, at least in terms of the occurrence of anemia.
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Affiliation(s)
- Ayako Urabe
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Ryotaro Sakamori
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Yuki Tahata
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Ryoko Yamada
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | | | | | | | | | | | | | - Taizo Hijioka
- National Hospital Organization Osaka Minami Medical Center, Kawachinagano, Japan
| | - Takahiro Kodama
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Hayato Hikita
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Tomohide Tatsumi
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
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