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Thi Thu PN, Hoang Van D, Ngo Thi Quynh M, Tran Thi N, Pham Minh K, Pham Van L. Metabolic, renal, and hematological changes in chronic hepatitis C patients achieving rapid virologic response after 12 weeks of direct-acting antiviral treatment: A prospective cohort study. PLoS One 2023; 18:e0290235. [PMID: 37656689 PMCID: PMC10473482 DOI: 10.1371/journal.pone.0290235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Accepted: 08/05/2023] [Indexed: 09/03/2023] Open
Abstract
The impact of direct-acting antivirals (DAA) therapy on lipid and glucose metabolism and kidney function in patients with hepatitis C virus (HCV) infection, along with its side effects on blood cells, remains controversial. Therefore, we conducted a study that enrolled 280 patients with HCV infection who achieved sustained virologic response after treatment with DAA therapy without ribavirin to evaluate the metabolic changes, renal function, and anemia risk based on real-world data. This study was an observational prospective study with a follow-up period of 12 weeks after the initiation of DAA therapy. Data on biochemical tests, renal function, blood counts, viral load, and host genomics were recorded before treatment and after 12 weeks of treatment with DAAs. DAA therapy reduced fibrosis-4 scores and improved liver function, with significant reductions in aspartate transaminase, alanine aminotransferase, and total bilirubin levels. However, DAA therapy slightly increased uric acid, cholesterol, and low-density lipoprotein cholesterol levels. It significantly reduced fasting blood glucose levels and hemoglobin A1C index (HbA1C) in the study group, while hemoglobin (Hb) and hematocrit (HCT) concentrations decreased significantly (4.78 ± 21.79 g/L and 0.09% ± 0.11%, respectively). The estimated glomerular filtration rate (eGFR) decreased by 12.89 ± 39.04 mL/min/1.73m2. Most variations were not related to the genotype, except for Hb, HCT, and HbA1C. Anemia incidence increased from 23.58% before treatment to 30.72% after treatment. Patients with HCV-1 genotype had a higher rate of anemia than did patients with genotype 6 (36.23% vs. 24.62%). Multivariate analysis showed that the risk of anemia was related to female sex, cirrhosis status, fibrosis-4 score, pretreatment eGFR, and pretreatment Hb level. The results of our study can provide helpful information to clinicians for the prognosis and treatment of HCV infection.
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Affiliation(s)
- Phuong Nguyen Thi Thu
- Haiphong International Hospital, Haiphong, Vietnam
- Hai Phong University of Medicine and Pharmacy, Hai Phong, Vietnam
| | | | | | - Ngan Tran Thi
- Haiphong International Hospital, Haiphong, Vietnam
- Hai Phong University of Medicine and Pharmacy, Hai Phong, Vietnam
| | - Khue Pham Minh
- Hai Phong University of Medicine and Pharmacy, Hai Phong, Vietnam
| | - Linh Pham Van
- Hai Phong University of Medicine and Pharmacy, Hai Phong, Vietnam
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Lee J, Ahn SB, Yim SY, An J, Jun DW, Ko MJ, Park DA, Yoo JJ. Efficacy and safety of direct-acting antiviral therapy for hepatitis C virus in elderly patients (≥65 years old): A systematic review and meta-analysis. J Viral Hepat 2022; 29:496-517. [PMID: 35357774 DOI: 10.1111/jvh.13679] [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] [Received: 09/13/2021] [Revised: 02/07/2022] [Accepted: 03/11/2022] [Indexed: 12/09/2022]
Abstract
Direct-acting agents (DAAs) have launched a new era of hepatitis C virus (HCV) treatment. As aged individuals comprise a large percentage of HCV-infected patients, the effectiveness and safety of DAAs in the elderly have come under scrutiny. This meta-analysis aimed to evaluate the efficacy and safety of DAAs in elderly patients. After a systematic search in PubMed (MEDLINE), Embase, OVID MEDLINE, the Cochrane Library and other databases, two investigators reviewed relevant abstracts and selected manuscripts for examination. The sustained virologic response (SVR) and adverse event (AE) rates were calculated with a random-effects model. Ninety studies evaluating SVR rates of elderly patients (≥65 years old) receiving DAAs were selected. DAAs in elderly patients exhibited a notable SVR rate of 96% (95% confidence interval [CI]: 95%-97%), accompanied by comparable rates in subgroup analyses. The comparison of SVR rates in elderly and non-elderly patients indicated no significant discrepancy (odds ratio [OR] 1.01, 95% CI: 1.00-1.01). The overall event rate of AEs was 45% (95% CI: 31%-60%), though AE rates varied by subgroups. Furthermore, AEs were comparatively more frequent (OR 1.15, 95% CI: 1.04-1.28) in the elderly than non-elderly, especially in subgroups such as SAE (OR 1.89, 95% CI: 1.52-2.36) and dose reduction in ribavirin (OR 1.90, 95% CI: 1.53-2.36). However, in the ribavirin (RBV)-free regimen, there was no significant difference in the incidence of AEs between the elderly and non-elderly groups. DAAs have high efficacy in elderly patients. Considering the possibility of AE, the RBV-free regimen should be given prior consideration for the treatment of elderly patients with HCV.
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Affiliation(s)
- Jieun Lee
- College of Medicine, Soonchunhyang University, Cheonan, Korea
| | - Sang Bong Ahn
- Nowon Eulji Medical Center, Department of Internal Medicine, Eulji University College of Medicine, Seoul, Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University Hospital, Seoul, Korea
| | - Jihyun An
- Gastroenterology and Hepatology, Hanyang University College of Medicine, Guri, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Min Jung Ko
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency (NECA), Seoul, Korea
| | - Dong Ah Park
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency (NECA), Seoul, Korea
| | - Jeong-Ju Yoo
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
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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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Xia H, Zhang Y, Zaongo SD, Liang J, Gong X, Hu Y, Ma P, Wang F. Direct-acting antiviral treatments display excellent outcomes even in older HCV-infected patients at increased risk of fibrosis. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:847. [PMID: 34164481 PMCID: PMC8184475 DOI: 10.21037/atm-21-1297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Background This study compared the efficacy and tolerability of available direct-acting antiviral (DAA) regimens between individuals aged 60 years and older and younger patients in a real-life setting. Specifically, we aimed to provide evidence of the efficacy and safety of DAAs in the treatment of older adults in Tianjin, China. Methods In this retrospective observational cohort study, patients with chronic hepatitis C virus (HCV) were enrolled between April 2018 and December 2019 at 2 tertiary hospitals in Tianjin, China. We assessed the sustained virologic response (SVR) 12 weeks (SVR12) after DAA treatment, and adverse events in two groups using age stratification by comparing older adults (≥60 years) and younger adults (<60 years). Logistic regression analyses were performed to explore the risk factors associated with the SVR12. Results Of 1,106 patients, 440 (39.8%) were ≥60 years of age. The overall SVR12 rate was 97.8% in the entire cohort. In the older adult group, the SVR12 rate was 98.0% (431/440) compared to 97.7% (651/666) in the younger adult group. A multivariate analysis showed that (I) age was not predictive of SVR; and (II) the variables of treatment-experience [adjusted odds ratio (aOR) =27.53; 95% confidence interval (CI) =3.35–226.08; P=0.002] and aspartate aminotransferase (AST) (aOR =1.02; 95% CI =1.01–1.04; P=0.027) were independently associated with the SVR12 in the older adult group. All of the available DAA regimens were well-tolerated in older adult group. Conclusions Chinese older adults with chronic HCV infection showed a significantly higher percentage of fibrosis; however, the available different DAA regimens were safe, well-tolerated, and achieved high rates of SVR in all age subgroups. Our observations suggest that DAA treatment should not be withheld even from older patients suffering from chronic HCV.
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Affiliation(s)
- Huan Xia
- Department of Infectious Diseases, Tianjin Second People's Hospital, Tianjin, China.,Tianjin Association of STD/AIDS Prevention and Control, Tianjin, China
| | - Yaping Zhang
- The Third Central Clinical College of Tianjin Medical University, Tianjin, China
| | - Silvere D Zaongo
- Department of Infectious Diseases, Tianjin Second People's Hospital, Tianjin, China
| | - Jing Liang
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin, China
| | - Xiaowen Gong
- State Key Laboratory of Experimental Hematology, National Clinical Research Centre for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| | - Yue Hu
- Department of Infectious Diseases, Tianjin Second People's Hospital, Tianjin, China
| | - Ping Ma
- Department of Infectious Diseases, Tianjin Second People's Hospital, Tianjin, China.,Tianjin Association of STD/AIDS Prevention and Control, Tianjin, China
| | - Fengmei Wang
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin, China
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Masaki N, Kawasaki Y, Nozaki Y, Yanase M. Characteristics of patients aged over 75 years with hepatitis C virus infection treated with direct-acting antivirals in Japan: Evidence based on the nationwide, real-world database in Japan. Hepatol Res 2021; 51:417-425. [PMID: 33217105 DOI: 10.1111/hepr.13596] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 10/16/2020] [Accepted: 11/09/2020] [Indexed: 01/01/2023]
Abstract
AIM Direct-acting antivirals (DAAs) have dramatically changed the treatment of chronic hepatitis C. Their high efficacy helps in eradicating hepatitis C virus with few adverse events. Information on real-world use of DAAs therapy in patients aged 75 years and older is inadequate. METHODS The Japanese DAAs database was constructed in 2014 as a cooperative system between 18 prefectures. The medical reports filled in by doctors and anonymized at the local government office were collected. The patients' demographic features, viral factors, and treatment characteristics were compared among three groups stratified by age when therapy was initiated: Group A (<60 years old), Group B (60-74 years old), and Group C (≥75 years old). RESULTS Out of the 22,454 patients whose age upon starting therapy could be identified, 24.8% (n = 5597) belonged to Group C, which was ten times the number in the Japanese Interferon Database. Female patients, advanced stages of liver fibrosis, and past history of hepatocellular carcinoma treatment were significantly higher in the older age groups (Group A < B < C), whereas sustained virologic response (SVR) rates were not different (91%-93%). In Group C, multivariate logistic regression analysis revealed that predicting factors for virologic response varied among DAAs regimens. However, the completion of DAAs therapy commonly contributed to SVR, regardless of DAAs regimen. CONCLUSIONS DAAs therapy is associated with high SVR rates, even in the oldest age group, and therapy should not be withheld on the basis of old age.
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Affiliation(s)
- Naohiko Masaki
- Laboratory Testing Department, National Center for Global Health and Medicine, Tokyo, Japan
| | - Youhei Kawasaki
- Biostatistics Section, Clinical Research Center, Chiba University Hospital, Chiba, Japan
- Faculty of Nursing, Japanese Red Cross College of Nursing, Tokyo, Japan
| | - Yuichi Nozaki
- Department of Gastroenterology, National Center for Global Health and Medicine, Tokyo, Japan
| | - Mikio Yanase
- Department of Gastroenterology, National Center for Global Health and Medicine, Tokyo, Japan
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Parmar P, Shafran SD, Borgia SM, Doucette K, Cooper CL. Hepatitis C direct-acting antiviral outcomes in patients 75 years and older. JGH OPEN 2020; 5:253-257. [PMID: 33553664 PMCID: PMC7857276 DOI: 10.1002/jgh3.12480] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 12/07/2020] [Accepted: 12/08/2020] [Indexed: 12/17/2022]
Abstract
Background and Aim Elderly patients with hepatitis C virus (HCV) infection have worse interferon‐based treatment outcomes than young patients. Direct‐acting antiviral (DAA) regimens have enabled the treatment of previously difficult‐to‐cure populations. There are few studies that specifically assess DAA treatment outcomes in patients over 75 years of age. Methods Design: This was a cohort study. Setting: The setting was three Canadian HCV specialty sites. Participants: Patients aged 75 years and older and treated with DAA without interferon were enrolled. Measurements: Patient demographics, liver fibrosis by transient elastography, treatment regimen, and treatment outcome data were collected. Results The mean age of 78 patients in our analysis was 78.6 years (SD 3.5; range: 75–88 years). The most common genotype was 1b (35%). The most frequently utilized regimens included sofosbuvir‐velpatasvir (33%) and ledipasvir‐sofosbuvir (32%). Ribavirin was included for 17% of recipients. Sustained virological response (SVR) was achieved in 94% of patients (69% of those receiving ribavirin and 98% of patients on ribavirin‐free regimens). Ribavirin toxicity contributed to the lower SVR rates in ribavirin‐exposed patients. Ribavirin dosage was decreased in three patients and ultimately discontinued in two of these patients. All treatment was discontinued in another two patients. Conclusion Ribavirin‐free DAA therapy is safe and achieves SVR rates in older adults comparable to those described in the general population. RBV inclusion frequently results in complications, often leads to treatment modification or interruption, and does not improve SVR rates in those with advanced age.
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Affiliation(s)
- Parmvir Parmar
- Department of Medicine University of Ottawa Ottawa Ontario Canada.,The Ottawa Hospital Research Institute Ottawa Ontario Canada
| | - Stephen D Shafran
- Department of Medicine University of Alberta Edmonton Alberta Canada
| | - Sergio M Borgia
- William Osler Health Centre Brampton Civic Hospital Brampton Ontario Canada
| | - Karen Doucette
- Department of Medicine University of Alberta Edmonton Alberta Canada
| | - Curtis L Cooper
- Department of Medicine University of Ottawa Ottawa Ontario Canada.,The Ottawa Hospital Research Institute Ottawa Ontario Canada
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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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Watanabe S, Morimoto N, Miura K, Murohisa T, Tahara T, Sato T, Tano S, Fukaya Y, Kurata H, Okamura Y, Numao N, Uehara K, Murayama K, Nakazawa K, Sugaya H, Yoshizumi H, Iijima M, Tsukui M, Hirosawa T, Takaoka Y, Nomoto H, Maeda H, Goka R, Isoda N, Yamamoto H. Efficacy and safety of glecaprevir and pibrentasvir combination therapy in old-aged patients with chronic hepatitis C virus infection. J Rural Med 2020; 15:139-145. [PMID: 33033533 PMCID: PMC7530586 DOI: 10.2185/jrm.2020-004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Accepted: 04/23/2020] [Indexed: 12/11/2022] Open
Abstract
Objective: Combination therapy with glecaprevir and pibrentasvir (G/P) has
been shown to provide a sustained virologic response (SVR) rate of >97% in patients
with chronic hepatitis C virus (HCV) infection in the first published real-world Japanese
data. However, a recently published study showed that the treatment was often discontinued
in patients ≥75 years old, resulting in low SVR in intention-to-treat (ITT) analysis.
Thus, our aim was to evaluate real-world data for G/P therapy in patients ≥75 years of
age, the population density of which is high in “rural” regions. Patients and Methods: We conducted a multicenter study to assess the
efficacy and safety of G/P therapy for chronic HCV infection, in the North Kanto area in
Japan. Results: Of the 308 patients enrolled, 294 (95.5%) completed the treatment
according to the protocol. In ITT and per-protocol analyses, the overall SVR12 rate was
97.1% and 99.7%, respectively. The old-aged patients group consisted of 59 participants,
56 of whom (94.9%) completed the scheduled protocol. Although old-aged patients tended to
have non-SVR factors such as liver cirrhosis, history of HCC, and prior DAA therapies, the
SVR12 rates in old-aged patients were 98.3% and 100% in the ITT and PP analyses,
respectively. Of 308 patients enrolled, adverse events were observed in 74 patients
(24.0%), with grade ≥3 events in 8 patients (2.6%). There was no significant difference in
any grade and grade ≥3 adverse events between the old-aged group and the rest of the study
participants. Only one patient discontinued the treatment because of adverse events. Conclusion: G/P therapy is effective and safe for old-aged patients.
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Affiliation(s)
- Shunji Watanabe
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Naoki Morimoto
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Kouichi Miura
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | | | - Toshiyuki Tahara
- Department of Gastroenterology, Saiseikai Utsunomiya Hospital, Japan
| | - Takashi Sato
- Department of Gastroenterology, Nasu Red Cross Hospital, Japan
| | - Shigeo Tano
- Department of Gastroenterology, Shin-Oyama City Hospital, Japan
| | - Yukimura Fukaya
- Department of Internal Medicine, Nasu Minami Hospital, Japan
| | - Hidekazu Kurata
- Department of Gastroenterology, Tochigi Medical Center Shimotsuga, Japan
| | | | - Norikatsu Numao
- Department of Gastroenterology, Haga Red Cross Hospital, Japan
| | - Keita Uehara
- Department of Gastroenterology, Tochigi Medical Center, Japan
| | - Kozue Murayama
- Department of Gastroenterology, Koga Red Cross Hospital, Japan
| | | | - Hitoshi Sugaya
- Department of Internal Medicine, Utsunomiya Higashi Hospital, Japan.,Department of Gastroenterology, Ashikaga Red Cross Hospital, Japan
| | | | - Makoto Iijima
- Department of Gastroenterology, Dokkyo Medical University, Japan.,Department of Gastroenterology, Yuai Memorial Hospital, Japan
| | - Mamiko Tsukui
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Takuya Hirosawa
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Yoshinari Takaoka
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Hiroaki Nomoto
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Hiroshi Maeda
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Rie Goka
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Norio Isoda
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
| | - Hironori Yamamoto
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Japan
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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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10
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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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11
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Villani R, Monami M, Di Cosimo F, Fioravanti G, Mannucci E, Vendemiale G, Serviddio G. Direct-acting antivirals for HCV treatment in older patients: A systematic review and meta-analysis. J Viral Hepat 2019; 26:1249-1256. [PMID: 31243849 DOI: 10.1111/jvh.13169] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 05/14/2019] [Accepted: 05/15/2019] [Indexed: 12/13/2022]
Abstract
The advent of highly effective and well-tolerated direct antiviral antivirals (DAAs) has dramatically changed the landscape of chronic hepatitis C. The effect of DAAs in older adults is difficult to determine since patients aged ≥ 65 years were too few in most clinical trials and data mainly come from observational studies. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of DAAs in patients aged 65 and older. PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, HCV-Trials.com databases were searched for literature published until 1 December 2017. English language articles reporting results of phase 2 or 3 randomized controlled trials (RCTs), single-arm clinical trials (SATs) and observational studies were included in the final analysis. All studies included subgroups of older patients and compared their outcomes with younger individuals. By using a random-effects or fixed-effects model, odds ratio (OR) was calculated for the efficacy and safety. Heterogeneity was tested using I2 statistics. Thirty-seven studies reported data on the DAA efficacy. The OR was 1.66 (95%CI: 1.00-2.75; P = 0.06) in meta-analysis of RCTs, and similar results were found in SATs and observational studies. HCV genotype, stage of fibrosis or HIV co-infection did not affect the rate of SVR in older persons. Prevalence of anaemia (OR 0.26 95%CI: 0.09-0.69; P = 0.007) (OR 0.25 95%CI: 0.09-0.69; P = 0.007) and skin complaints (OR 0.61 95%CI: 0.45-0.83; P = 0.001) was higher in older adults. Finally, geriatric patients affected by chronic HCV infection can be safely treated with DAAs with the same efficacy reported in younger adults.
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Affiliation(s)
- Rosanna Villani
- C.U.R.E. (University Centre for Liver Disease Research and Treatment), Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Matteo Monami
- Diabetology, Azienda Ospedaliero Universitaria Careggi and University of Florence, Florence, Italy
| | - Francesca Di Cosimo
- C.U.R.E. (University Centre for Liver Disease Research and Treatment), Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Gilda Fioravanti
- C.U.R.E. (University Centre for Liver Disease Research and Treatment), Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Edoardo Mannucci
- Diabetology, Azienda Ospedaliero Universitaria Careggi and University of Florence, Florence, Italy
| | - Gianluigi Vendemiale
- C.U.R.E. (University Centre for Liver Disease Research and Treatment), Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Gaetano Serviddio
- C.U.R.E. (University Centre for Liver Disease Research and Treatment), Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
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12
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Pan CQ, Gayam V, Rabinovich C, Normatov M, Fidman B, Wang D, Garlapati P. Efficacy of Direct-Acting Antivirals for Chronic Hepatitis C in a Large Cohort of Older Adults in the United States. J Am Geriatr Soc 2019; 68:379-387. [PMID: 31647119 DOI: 10.1111/jgs.16206] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 09/04/2019] [Accepted: 09/08/2019] [Indexed: 12/25/2022]
Abstract
OBJECTIVES Data on the virologic response and tolerability of direct-acting antivirals (DAAs) are lacking in older people because these individuals are underrepresented in clinical trials. This study aimed to assess the effectiveness and tolerability of DAA regimens in older individuals in a large cohort of real-life clinical practice. METHODS In this retrospective study, patients with chronic hepatitis C infection between 2017 and 2018 were divided into patients aged 65 years and older and those younger than 65 years. We evaluated the sustained virologic response rates (SVRs) in both groups. Further subgroup analyses on the SVRs for patients aged 65 to 74, 75 to 84, and 85 years and older were performed. We also analyzed the predictors of treatment response in older individuals. RESULTS Among 1151 eligible patients, 516 were in the older group and 635 were in the younger group. The overall treatment response in the entire cohort was 97.7%. A significantly higher percentage of patients presented with advanced stages of fibrosis in the older group (53.1% vs 39.5%; P = <.001). The SVR rates were similar between the two groups (98.3% vs 97.7%; P = .18). In multivariate models, age was not predictive of SVR after adjusting for confounders. Subgroup analyses in the age groups of 65 to 74, 75 to 84, and older than 85 years showed similar treatment response rates (97.4%, 97.2%, and 86.7, respectively; P = .06) and advanced fibrosis (50.8%, 61.5%, and 53.3%, respectively; P = .14). CONCLUSION Although older people exhibit a significantly higher frequency of fibrosis, DAAs produce high rates of SVR in all age groups, and the age of the patient does not seem to have a significant impact on the efficacy of DAAs including patients in the oldest age category (≥75 y). Treatment should not be withheld in older individuals. J Am Geriatr Soc 68:379-387, 2020.
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Affiliation(s)
- Calvin Q Pan
- Center of Liver Diseases, Capital Medical University Affiliated Beijing Ditan Hospital, Chaoyang District, Beijing, China.,Division of Gastroenterology and Hepatology, NYU Langone Health, New York University School of Medicine, New York, New York
| | - Vijay Gayam
- Interfaith Medical Center, SUNY Downstate University Hospital, Brooklyn, New York
| | | | | | | | - Dan Wang
- St. John's University, Jamaica, New York
| | - Pavani Garlapati
- Interfaith Medical Center, SUNY Downstate University Hospital, Brooklyn, New York
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13
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Ji F, Yeo YH, Wei MT, Ogawa E, Enomoto M, Lee DH, Iio E, Lubel J, Wang W, Wei B, Ide T, Preda CM, Conti F, Minami T, Bielen R, Sezaki H, Barone M, Kolly P, Chu PS, Virlogeux V, Eurich D, Henry L, Bass MB, Kanai T, Dang S, Li Z, Dufour JF, Zoulim F, Andreone P, Cheung RC, Tanaka Y, Furusyo N, Toyoda H, Tamori A, Nguyen MH. Sustained virologic response to direct-acting antiviral therapy in patients with chronic hepatitis C and hepatocellular carcinoma: A systematic review and meta-analysis. J Hepatol 2019; 71:473-485. [PMID: 31096005 DOI: 10.1016/j.jhep.2019.04.017] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Revised: 03/31/2019] [Accepted: 04/25/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The effect of hepatocellular carcinoma (HCC) on the response to interferon-free direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C (CHC) infection remains unclear. Using a systematic review and meta-analysis approach, we aimed to investigate the effect of DAA therapy on sustained virologic response (SVR) among patients with CHC and either active, inactive or no HCC. METHODS PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from 1/1/2013 to 9/24/2018. The pooled SVR rates were computed using DerSimonian-Laird random-effects models. RESULTS We included 49 studies from 15 countries, comprised of 3,341 patients with HCC and 35,701 without HCC. Overall, the pooled SVR was lower in patients with HCC than in those without HCC (89.6%, 95% CI 86.8-92.1%, I2 = 79.1% vs. 93.3%, 95% CI 91.9-94.7%, I2 = 95.0%, p = 0.0012), translating to a 4.8% (95% CI 0.2-7.4%) SVR reduction by meta-regression analysis. The largest SVR reduction (18.8%) occurred in patients with active/residual HCC vs. inactive/ablated HCC (SVR 73.1% vs. 92.6%, p = 0.002). Meanwhile, patients with HCC who received a prior liver transplant had higher SVR rates than those who did not (p <0.001). Regarding specific DAA regimens, patients with HCC treated with ledipasvir/sofosbuvir had lower SVR rates than patients without HCC (92.6%, n = 884 vs. 97.8%, n = 13,141, p = 0.026), but heterogeneity was high (I2 = 84.7%, p <0.001). The SVR rate was similar in patients with/without HCC who were treated with ombitasvir/paritaprevir/ritonavir ± dasabuvir (n = 101) (97.2% vs. 94.8%, p = 0.79), or daclatasvir/asunaprevir (91.7% vs. 89.8%, p = 0.66). CONCLUSION Overall, SVR rates were lower in patients with HCC, especially with active HCC, compared to those without HCC, though heterogeneity was high. Continued efforts are needed to aggressively screen, diagnose, and treat HCC to ensure higher CHC cure rates. LAY SUMMARY There are now medications (direct-acting antivirals or "DAAs") that can "cure" hepatitis C virus, but patients with hepatitis C and liver cancer may be less likely to achieve cure than those without liver cancer. However, patients with liver cancer are also more likely to have advanced liver disease and risk factors that can decrease cure rates, so better controlled studies are needed to confirm these findings.
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Affiliation(s)
- Fanpu Ji
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China; Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA; National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China; Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Yee Hui Yeo
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Mike Tzuhen Wei
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Eiichi Ogawa
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA; Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Masaru Enomoto
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Dong Hyun Lee
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA; Division of Gastroenterology, Department of Internal Medicine, Good Gang-An Hospital, Busan, Republic of Korea
| | - Etsuko Iio
- Department of Virology & Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan
| | - John Lubel
- Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Wenjun Wang
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Bin Wei
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Tatsuya Ide
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan
| | - Carmen Monica Preda
- University of Medicine and Pharmacy "Carol Davila", Department of Gastroenterology and Hepatology, Clinical Institute Fundeni, Bucharest, Romania
| | - Fabio Conti
- Research Centre for the Study of Hepatitis, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Tatsuya Minami
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | - Rob Bielen
- Faculty of Medicine and Life Sciences, Hasselt University, Belgium
| | - Hitomi Sezaki
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Michele Barone
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, Azienda Universitario-Ospedaliera Policlinico, University of Bari, Bari, Italy
| | - Philippe Kolly
- Department of Clinical Research, University of Bern, Bern, Switzerland; University Clinic of Visceral Surgery and Medicine, Inselspital Bern, Bern, Switzerland
| | - Po-Sung Chu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Victor Virlogeux
- Department of Hepatology, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France
| | - Dennis Eurich
- Department of Surgery Campus Charité Mitte / Campus Virchow-Klinikum, Berlin, Germany
| | - Linda Henry
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Michelle B Bass
- Lane Medical Library & Knowledge Management Center, Stanford University, Palo Alto, CA, USA
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Shuangsuo Dang
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Zongfang Li
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China; Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Jean-François Dufour
- Department of Clinical Research, University of Bern, Bern, Switzerland; University Clinic of Visceral Surgery and Medicine, Inselspital Bern, Bern, Switzerland
| | - Fabien Zoulim
- Department of Hepatology, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France; Cancer Research Center of Lyon (CRCL-INSERM U1052), Lyon University, Lyon, France
| | - Pietro Andreone
- Research Centre for the Study of Hepatitis, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Ramsey C Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA; Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA
| | - Yasuhito Tanaka
- Department of Virology & Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan
| | - Norihiro Furusyo
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Akihiro Tamori
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.
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14
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Mücke MM, Herrmann E, Mücke VT, Graf C, Zeuzem S, Vermehren J. Efficacy and safety of direct-acting antivirals for hepatitis C in the elderly: A systematic review and meta-analysis. Liver Int 2019; 39:1652-1660. [PMID: 31033122 DOI: 10.1111/liv.14126] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Accepted: 04/19/2019] [Indexed: 01/08/2023]
Abstract
BACKGROUND&AIMS Since the introduction of direct-acting antivirals (DAAs) several studies have reported high efficacy and safety in Hepatitis C infected patients, even in those earlier considered difficult-to-treat. We aimed to assess the efficacy and safety of DAA therapy in elderly patients. METHODS The PubMed MEDLINE, Embase and Cochrane databases were searched through July 2018. Two independent researchers extracted data and assessed the quality and risk of bias. Risk ratios (RRs) were pooled using random effects models. The primary outcome was efficacy of DAA therapy assessed by the RR for non-sustained virologic response (SVR) among patients aged <65 vs ≥65 years. RESULTS Overall, we identified 63 studies including 34 082 patients treated with different DAAs. Risk for non-SVR was comparable in patients <65 and ≥65 years of age (RR 1.00, 95% CI 0.86-1.15; P = 0.979) and even lower in a subgroup analysis of cirrhotic patients ≥65 years of age (RR 0.59, 95% CI 0.35-0.99, P = 0.044). Risk for non-SVR was similar between age groups in all other subgroup analyses. Elderly patients had a significantly increased risk of adverse events (AEs) (RR 1.30, 95% CI 1.11-1.52, P = 0.001), but not for serious adverse events (P = 0.43) or treatment discontinuation (P = 0.15). Risk for anaemia if treated with additional ribavirin was 2.84 (95% CI 1.73-4.66, P < 0.001) in elderly patients compared to patients <65 years. CONCLUSION Our results show that DAAs are highly effective and safe in elderly patients. Ribavirin should be avoided in the elderly as more AEs and particularly anaemia is observed. Further cost-effectiveness analyses are needed to evaluate the socio-economic benefit of treating elderly people without advanced liver disease.
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Affiliation(s)
- Marcus M Mücke
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Eva Herrmann
- Institute of Biostatistics and Mathematical Modeling, Goethe University, Frankfurt am Main, Germany
| | - Victoria T Mücke
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Christiana Graf
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Stefan Zeuzem
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Johannes Vermehren
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany
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15
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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: 7] [Impact Index Per Article: 1.2] [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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16
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Igarashi A, Furusyo N, Ogawa E, Nomura H, Dohmen K, Higashi N, Takahashi K, Kawano A, Azuma K, Satoh T, Nakamuta M, Koyanagi T, Kato M, Shimoda S, Kajiwara E, Hayashi J. Cost-effectiveness analysis of sofosbuvir plus ribavirin in patients with genotype 2 chronic hepatitis C: an analysis with real world outcomes from a multicentre cohort in Japan. BMJ Open 2019; 9:e023405. [PMID: 31221866 PMCID: PMC6588956 DOI: 10.1136/bmjopen-2018-023405] [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] [Indexed: 11/03/2022] Open
Abstract
OBJECTIVES A number of publications have demonstrated the cost-effectiveness of sofosbuvir plus ribavirin (SOF+RBV) compared with the former standard therapy with interferon (IFN)-containing regimens. Unlike these cost-effective analyses, where efficacy parameters were obtained from registration trials for drug approval, this analysis is a cost-effectiveness analysis of SOF+RBV for genotype (GT) 2 non-cirrhosis (NC) and compensated cirrhosis (CC) patients using efficacy parameters obtained from a multicentre cohort study (Kyushu University Liver Disease Study; KULDS) in Kyushu area in Japan in order to reflect real-world clinical practice in Japan. METHOD A Markov model followed 10 000 patients (62 years old) over their lifetime. Four populations were followed: treatment-naïve (TN)-NC, treatment-experienced (TE)-NC, TN-CC and TE-CC. Comparators were Peg-IFNα2b+RBV for TN-NC and CC patients and telaprevir (TVR)+Peg-IFNα2b+RBV for TE-NC patients. The sustained virological response (SVR) rates of SOF+RBV were taken from KULDS and those of comparators were obtained from systematic literature reviews. There were nine states (NC, CC, decompensated cirrhosis [DC], hepatocellular carcinoma [HCC], SVR [NC], SVR [CC], liver transplantation [LT], post-LT and death) in this model, and an increase in the progression rate to HCC due to ageing was also considered. The analysis was conducted from the perspective of a public healthcare payer, and a discount rate of 2% was set for both cost and effectiveness. RESULTS Incremental cost-effectiveness ratios (ICERs) of SOF+RBV versus Peg-IFNα2b+RBV were ¥323 928 /quality-adjusted life year (QALY) for TN-NC patients, ¥92 256/QALY for TN-CC patients and ¥1 519 202/QALY for TE-CC patients. The ICER of SOF+RBV versus TVR+Peg-IFNα2b+RBV was ¥849 138/QALY for TE-NC patients. The robustness of the results was determined by sensitivity analysis. CONCLUSIONS The results of this analysis strongly demonstrate the robustness of our previous findings that SOF+RBV regimens are cost-effective in the real world and clinical trial settings for Japanese GT2 NC and CC patients.
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Affiliation(s)
- Ataru Igarashi
- Department of Health Economics and Outcomes Research, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo, Tokyo, Japan
- Unit of Public Health and Preventive Medicine, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan
| | - Norihiro Furusyo
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Eiichi Ogawa
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Hideyuki Nomura
- The Center for Liver Disease, Shin-Kokura Hospital, Kitakyushu, Japan
| | - Kazufumi Dohmen
- Department of Internal Medicine, Chihaya Hospital, Fukuoka, Japan
| | - Nobuhiko Higashi
- Department of Hepatology, Steel Memorial Yawata Hospital, Kitakyushu, Japan
| | | | - Akira Kawano
- Department of Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan
| | - Koichi Azuma
- Department of Medicine, Kyushu Central Hospital, Fukuoka, Japan
| | - Takeaki Satoh
- Center for Liver Disease, National Hospital Organization Kokura Medical Center, Kitakyushu, Japan
| | - Makoto Nakamuta
- Department of Gastroenterology, Kyushu Medical Center, National Hospital Organization, 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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17
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Ogawa E, Furusyo N, Nakamuta M, Nomura H, Satoh T, Takahashi K, Koyanagi T, Kajiwara E, Dohmen K, Kawano A, Ooho A, Azuma K, Kato M, Shimoda S, Hayashi J. Glecaprevir and pibrentasvir for Japanese patients with chronic hepatitis C genotype 1 or 2 infection: Results from a multicenter, real-world cohort study. Hepatol Res 2019; 49:617-626. [PMID: 30849206 DOI: 10.1111/hepr.13328] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2018] [Revised: 02/25/2019] [Accepted: 03/02/2019] [Indexed: 02/08/2023]
Abstract
AIM Glecaprevir (GLE) and pibrentasvir (PIB) are new direct-acting antiviral agents (DAAs) with pangenotypic inhibitors that respectively target the hepatitis C virus (HCV) NS3/4 protease and NS5A. The aim of this study was to evaluate the effectiveness and safety of combining GLE and PIB for patients with HCV genotype (GT) 1 or 2 infection in the clinical setting, including patients DAA-experienced or on hemodialysis. METHODS This multicenter, real-world, retrospective, cohort study consisted of 314 Japanese patients who were treated with GLE (300 mg) and PIB (120 mg) for a fixed 8- or 12-week duration. We evaluated the sustained virologic response rate 12 weeks after the end of treatment (SVR12) and adverse events. RESULTS Among the treated patients, 122 had GT1 and 192 GT2 infection. The overall SVR12 rates in the per-protocol populations were 99.2% (119/120) for GT1 and 98.9% (183/185) for GT2. High SVR12 rates were observed in almost all subgroups, including cirrhosis, receiving hemodialysis, or previous all-oral DAA groups treated with asunaprevir and daclatasvir (GT1b), ledipasvir/sofosbuvir (GT1), or sofosbuvir and ribavirin (GT2). Virological relapse occurred in only 1.0% (3/305) of the patients who completed treatment. The most common adverse events were pruritus and fatigue (>5% of patients). Serious adverse events were rare and discontinuation due to an adverse event was required for 1.6% of the patients. CONCLUSIONS In this real-world cohort study, treatment with GLE/PIB achieved high SVR12 rates with a low rate of serious adverse events among patients with HCV GT1 or 2 infection.
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Affiliation(s)
- Eiichi Ogawa
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Norihiro Furusyo
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Makoto Nakamuta
- Department of Gastroenterology, Kyushu Medical Center, National Hospital Organization, Fukuoka, Japan
| | - Hideyuki Nomura
- The Center for Liver Disease, Shin-Kokura Hospital, Kitakyushu, Japan
| | - Takeaki Satoh
- Center for Liver Disease, National Hospital Organization Kokura Medical Center, Kitakyushu, Japan
| | | | | | | | - Kazufumi Dohmen
- Department of Internal Medicine, Chihaya Hospital, Fukuoka, Japan
| | - Akira Kawano
- Department of Medicine, Kitakyushu Municipal 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
| | - 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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18
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Lv DD, Wang ML, Chen EQ, Wu DB, Tao YC, Zhang DM, Tang H. A retrospective study of the efficacy of sofosbuvir plus NS5A inhibitors for patients with hepatitis C virus genotype-2 chronic infection. Eur J Gastroenterol Hepatol 2019; 31:382-388. [PMID: 30383554 DOI: 10.1097/meg.0000000000001299] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND A combination of sofosbuvir (SOF)+NS5A inhibitor therapies is the main treatment for patients with hepatitis C virus (HCV) genotype-2 (GT-2) chronic infection, but the data are rarely reported in China. This study aimed to investigate the virological response and liver fibrosis improvement among GT-2 patients receiving SOF+NS5A inhibitors. PATIENTS AND METHODS In this retrospective study, patients who received SOF+NS5A inhibitors between March 2016 and July 2017 were recruited. The treatment duration was 12 weeks and the treatment strategies included SOF+daclatasvir, SOF/ledipasvir, and SOF/velpatasvir. The primary endpoint was a sustained virologic response (serum HCV RNA undetectable) at week 12 after the end of therapy and the secondary endpoint was the improvement in liver stiffness and scores of apartate aminotransferase to platelet ratio index and fibrosis-4. RESULTS A total of 30 GT-2 patients were enrolled, with 13 (43.3%) patients in SOF+daclatasvir, 13 (43.3%) patients in SOF/ledipasvir, and four (13.3%) patients in SOF/velpatasvir. All patients [30/30 (100%)] achieved SVR, irrespective of treatment regimens and degree of liver fibrosis. After the treatment, liver fibrosis scores of apartate aminotransferase to platelet ratio index (2.27±2.14 vs. 0.89±0.77, P=0.003) and fibrosis-4 (1.17±1.22 vs. 0.42±0.25, P=0.013) were both significantly lower than those before treatment. CONCLUSION SOF+NS5A inhibitor therapies may induce an excellent virological response and fibrosis improvement in HCV GT-2-infected patients.
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Affiliation(s)
- Duo-Duo Lv
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, People's Republic of China
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19
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Akahane T, Kurosaki M, Itakura J, Tsuji K, Joko K, Kimura H, Nasu A, Ogawa C, Kojima Y, Hasebe C, Wada S, Uchida Y, Sohda T, Suzuki H, Yoshida H, Kusakabe A, Tamada T, Kobashi H, Mitsuda A, Kondo M, Shigeno M, Ide Y, Morita A, Kitamura T, Abe T, Izumi N. Real-world efficacy and safety of sofosbuvir + ribavirin for hepatitis C genotype 2: A nationwide multicenter study by the Japanese Red Cross Liver Study Group. Hepatol Res 2019; 49:264-270. [PMID: 30171740 DOI: 10.1111/hepr.13246] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Revised: 08/15/2018] [Accepted: 08/27/2018] [Indexed: 12/15/2022]
Abstract
AIM This study aimed to describe the real-world efficacy and safety of sofosbuvir (SOF) + ribavirin (RBV) for chronic hepatitis C, genotype 2. METHODS This was a retrospective analysis of a nationwide, multicenter registry including 914 hepatitis C genotype 2 Japanese patients treated with SOF + RBV for 12 weeks. The rate of sustained virologic response at 12 weeks after treatment (SVR12), incidence of adverse events, and changes in serological parameters were analyzed. RESULTS Treatment was completed in 98.9% of patients. Ribavirin dose reduction was required in 29.7% of patients. The SVR12 rate was 96.8% in the intention-to-treat population and 97.6% in the per-protocol population. Factors associated with SVR12 were absence of advanced fibrosis (odds ratio, 5.76, P = 0.003) and interferon-treatment-naïve status (odds ratio, 4.79, P = 0.017). Dose reduction or total adherence of RBV was not associated with SVR. The resistance-associated substitution S282 T in NS5B was not detected in any patient at virologic failure. Serum albumin levels significantly increased, and the degree of increase was greater in patients with advanced fibrosis than in those without (0.21 ± 0.32 vs. 0.05 ± 0.29, P < 0.0001). Alpha-fetoprotein decreased significantly at end of treatment (P < 0.0001), and the degree of decrease was greater in patients with advanced fibrosis than in those without (21.7 ± 60.8 vs. 2.5 ± 15.5, P < 0.001). The most commonly reported adverse event was anemia (13.7%). CONCLUSIONS Treatment with SOF + RBV was highly effective and safe in Japanese patients with HCV genotype 2 infection.
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Affiliation(s)
- Takehiro Akahane
- Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
| | - Jun Itakura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
| | - Keiji Tsuji
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Kouji Joko
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Matsuyama, Japan
| | - Hiroyuki Kimura
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - Akihiro Nasu
- Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan
| | - Chikara Ogawa
- Department of Gastroenterology, Takamatsu Red Cross Hospital, Takamatsu, Japan
| | - Yuji Kojima
- Department of Hepatology, Japanese Red Cross Ise Hospital, Ise, Japan
| | - Chitomi Hasebe
- Department of Gastroenterology, Japanese Red Cross Asahikawa Hospital, Asahikawa, Japan
| | - Shuichi Wada
- Department of Gastroenterology, Nagano Red Cross Hospital, Nagano, Japan
| | - Yasushi Uchida
- Department of Gastroenterology, Matsue Red Cross Hospital, Matsue, Japan
| | - Tetsuro Sohda
- Department of Hepatology, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan
| | - Hideyuki Suzuki
- Department of Internal Medicine, Japanese Red Cross Haramachi Hospital, Haramachi, Japan
| | - Hideo Yoshida
- Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Atsunori Kusakabe
- Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan
| | - Takashi Tamada
- Department of Gastroenterology, Takatsuki Red Cross Hospital, Takatsuki, Osaka, Japan
| | - Haruhiko Kobashi
- Department of Hepatology, Japanese Red Cross Okayama Hospital, Okayama, Japan
| | - Akeri Mitsuda
- Department of Internal Medicine, Tottori Red Cross Hospital, Tottori, Japan
| | - Masahiko Kondo
- Department of Gastroenterology, Japanese Red Cross Otsu Hospital, Otsu, Japan
| | - Masaya Shigeno
- Department of Gastroenterology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan
| | - Yasushi Ide
- Department of Internal Medicine, Karatsu Red Cross Hospital, Karatsu, Japan
| | - Atsuhiro Morita
- Department of Gastroenterology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan
| | - Tadashi Kitamura
- Department of Gastroenterology, Shizuoka Red Cross Hospital, Shizuoka, Japan
| | - Takehiko Abe
- Department of Gastroenterology, Japanese Red Cross Maebashi Hospital, Maebashi, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
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20
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Hirosawa T, Morimoto N, Miura K, Tahara T, Murohisa T, Okamura Y, Sato T, Numao N, Imai M, Tano S, Murayama K, Kurata H, Ozawa I, Fukaya Y, Yoshizumi H, Watanabe S, Tsukui M, Takaoka Y, Nomoto H, Isoda N, Yamamoto H. No Regional Disparities in Sofosbuvir Plus Ribavirin Therapy for HCV Genotype 2 Infection in Tochigi Prefecture and Its Vicinity. Intern Med 2019; 58:477-485. [PMID: 30333396 PMCID: PMC6421161 DOI: 10.2169/internalmedicine.1194-18] [Citation(s) in RCA: 5] [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] [Indexed: 01/13/2023] Open
Abstract
Objective Regional disparities were observed in the outcomes of interferon (IFN)-based therapy for chronic hepatitis C virus (HCV) infection in a Japanese nationwide study. However, whether or not these regional disparities are observed in the outcomes of direct-acting antiviral drugs, including sofosbuvir (SOF) plus ribavirin (RBV) therapy, remains unclear. Methods We conducted a multicenter study to assess the efficacy of SOF plus RBV therapy for HCV genotype 2 infection in Tochigi Prefecture and its vicinity, in which IFN-based therapy yielded a low sustained virologic response (SVR) rate. In addition, we divided Tochigi Prefecture into six regions to examine regional disparities in the SVR. Patients We enrolled patients with chronic HCV genotype 2 infection. Results Of the 583 patients enrolled, 569 (97.6%) completed the treatment, and 566 (97.1%) also complied with post-treatment follow-up for 12 weeks. The overall SVR12 rate was 96.1% by per protocol and 93.7% by intention-to-treat analyses. No marked differences were observed in the SVR12 between subjects ≥65 and <65 years of age. Although large gaps were observed in the characteristics of patients and accessibility to medical resources, there was no significant difference in the SVR12 rate among the six regions in Tochigi Prefecture. Conclusion SOF plus RBV therapy was effective for HCV genotype 2 infection in an area where IFN-based therapy had previously shown unsatisfactory results. In addition, no regional disparities in the SVR12 were observed in Tochigi Prefecture.
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Affiliation(s)
- Takuya Hirosawa
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Japan
| | - Naoki Morimoto
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Japan
| | - Kouichi Miura
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Japan
| | - Toshiyuki Tahara
- Department of Gastroenterology, Saiseikai Utsunomiya Hospital, Japan
| | | | | | - Takashi Sato
- Department of Gastroenterology, Nasu Red Cross Hospital, Japan
| | - Norikatsu Numao
- Department of Gastroenterology, Haga Red Cross Hospital, Japan
| | - Masato Imai
- Department of Gastroenterological Surgery, Utsunomiya Memorial Hospital, Japan
| | - Shigeo Tano
- Department of Gastroenterology, Shin-Oyama City Hospital, Japan
| | - Kozue Murayama
- Department of Gastroenterology, Koga Red Cross Hospital, Japan
| | - Hidekazu Kurata
- Department of Gastroenterology, Tochigi Medical Center Shimotsuga, Japan
| | - Iwao Ozawa
- Department of Hepatobiliary Surgery, Tochigi Cancer Center, Japan
| | - Yukimura Fukaya
- Department of Internal Medicine, Nasu Minami Hospital, Japan
| | | | - Shunji Watanabe
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Japan
| | - Mamiko Tsukui
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Japan
| | - Yoshinari Takaoka
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Japan
| | - Hiroaki Nomoto
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Japan
| | - Norio Isoda
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Japan
| | - Hironori Yamamoto
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Japan
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21
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Pariente A, Arpurt JP, Remy AJ, Rosa-Hezode I, Causse X, Heluwaert F, Macaigne G, Henrion J, Renou C, Schnee M, Salloum H, Hommel S, Pilette C, Arotcarena R, Barjonet G, Lison H, Bourhis F, Jouannaud V, Pauwels A, Le-Bricquir Y, Geagea E, Condat B, Ripault MP, Zanditenas D, de Montigny-Lenhardt S, Labadie H, Tissot B, Maringe E, Cadranel JF, Hagege H, Lesgourgues B. Effects of Age on Treatment of Chronic Hepatitis C with Direct Acting Antivirals. Ann Hepatol 2019; 18:193-202. [PMID: 31113590 DOI: 10.5604/01.3001.0012.7912] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Accepted: 07/16/2018] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Data on the efficacy and tolerance of interferon-free treatment in chronic hepatitis C (CHC) in elderly patients are limited in phase II-III trials. MATERIAL AND METHODS A prospective cohort of adult patients with CHC treated in French general hospitals. RESULTS Data from 1,123 patients, distributed into four age groups, were analyzed. Of these, 278 were > 64 years old (fourth quartile) and 133 were > 73 years old (tenth decile). Elderly patients weighed less, were more frequently treatment-experienced women infected with genotype 1b or 2, while they less frequently had genotype 3 or HIV coinfection, but had more frequent comorbidities and drug consumption. Half of the patients had cirrhosis, whatever their ages. The main treatment regimens were sofosbuvir/ledipasvir (37.8%), sofosbuvir/daclatasvir (31.8%), sofosbuvir/simeprevir (16.9%), sofosbuvir/ribavirin (7.8%); ribavirin was given to 24% of patients. The overall sustained virological response (SVR) rate was 91.0 % (95% CI: 89.292.5%) with no difference according to age. Logistic regression of the independent predictors of SVR were albumin, hepatocellular carcinoma and treatment regimen, but not age. The rate of severe adverse events (66 in 59/1062 [5.6%] patients) tended to be greater in patients older than 64 years of age (21/261,8.1%), but the only independent predictors of SAE by logistic regression were cirrhosis and baseline hemoglobin. Patient-reported overall tolerance was excellent in all age groups, and patient-reported fatigue decreased during and after treatment, independent of age. CONCLUSIONS The high efficacy and tolerance of interferon-free regimens is confirmed in elderly patients in real-life conditions.
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Affiliation(s)
| | | | - Andre-Jean Remy
- Hepatogastroenterology Unit. Centre Hospitalier de Perpignan, France
| | - Isabelle Rosa-Hezode
- Hepatogastroenterology Unit. Centre Hospitalier Intercommunal de Creteil, France
| | - Xavier Causse
- Hepatogastroenterology Unit. Centre Hospitalier Regional d'Orieans, France
| | | | - Gilles Macaigne
- Hepatogastroenterology Unit. Centre Hospitalier de Marne-la-Vallee, France
| | - Jean Henrion
- Hepatogastroenterology Unit. Centre Hospitalier d'Haine-Saint-Paul, Belgium
| | - Christophe Renou
- Hepatogastroenterology Unit. Centre Hospitalier d'Hyeres, France
| | - Matthieu Schnee
- Hepatogastroenterology Unit. Centre Hospitalier de La-Roche-sur-Yon, France
| | - Hatem Salloum
- Hepatogastroenterology Unit. Centre Hospitalier de Meaux, France
| | - Severine Hommel
- Hepatogastroenterology Unit. Centre Hospitalier d'Aix-en-Provence, France
| | | | | | - Georges Barjonet
- Hepatogastroenterology Unit. Centre Hospitalier de Montelimar, France
| | - Hortensia Lison
- Hepatogastroenterology Unit. Centre Hospitalier de Creil, France
| | - Frangois Bourhis
- Hepatogastroenterology Unit. Centre Hospitalier de Chambery, France
| | - Vincent Jouannaud
- Hepatogastroenterology Unit. Centre Hospitalier de Montfermeil, France
| | - Arnaud Pauwels
- Hepatogastroenterology Unit. Centre Hospitalier de Gonesse, France
| | - Yann Le-Bricquir
- Hepatogastroenterology Unit. Centre Hospitalier de Beziers, France
| | - Edmond Geagea
- Hepatogastroenterology Unit. Centre Hospitalier de Cholet, France
| | - Bertrand Condat
- Hepatogastroenterology Unit. Centre Hospitalier de Bry-sur-Marne, France
| | | | - David Zanditenas
- Hepatogastroenterology Unit. Centre Hospitalier de Bry-sur-Marne, France
| | | | - Helene Labadie
- Hepatogastroenterology Unit. Centre Hospitalier de Saint-Denis, France
| | - Bertrand Tissot
- Hepatogastroenterology Unit. Centre Hospitalier du Mans, France
| | - Eric Maringe
- Hepatogastroenterology Unit. Centre Hospitalier de Beaune, France
| | | | - Herve Hagege
- Hepatogastroenterology Unit. Centre Hospitalier Intercommunal de Creteil, France
| | - Bruno Lesgourgues
- Hepatogastroenterology Unit. Centre Hospitalier de Montfermeil, France
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22
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Dultz G, Müller T, Petersen J, Mauss S, Zimmermann T, Muche M, Simon KG, Berg T, Zeuzem S, Hüppe D, Böker K, Wedemeyer H, Welzel TM. Effectiveness and Safety of Direct-Acting Antiviral Combination Therapies for Treatment of Hepatitis C Virus in Elderly Patients: Results from the German Hepatitis C Registry. Drugs Aging 2018; 35:843-857. [PMID: 30084012 DOI: 10.1007/s40266-018-0572-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND With the aging of the hepatitis C virus (HCV)-infected patient cohort and the availability of highly effective and tolerable treatment regimens, an increasing number of elderly patients are now eligible for HCV therapy. This study investigated clinical and epidemiologic characteristics of elderly HCV-infected patients as well as the effectiveness and safety of available therapies. METHODS Patients were enrolled into the German Hepatitis C Registry (DHC-R), a prospective, multicenter, real-world cohort study. Patients were treated at the discretion of the physician, and data were collected by a web-based system. RESULTS Of 7133 patients who initiated treatment, 686 (9.6%) were > 70 years of age. In patients > 70 years, intent-to-treat (ITT) SVR12 was 92.6% (514/555) compared to 90.7% (4521/4985) in patients ≤ 70 years of age. Overall, adverse events (AEs) were reported in 374 (54.5%) and 3435 patients (53.3%) > 70 or ≤ 70 years of age; 7.6% (52) and 3.6% (235) in the respective age groups had a serious AE. Twenty-two (3.2%) and 62 (1.0%) of the patients > 70 or ≤ 70 years discontinued treatment due to AEs. Death was reported in 34 patients, of whom eight were > 70 years of age. Frequent comorbidities in patients > 70 years of age were cardiac disease, renal disease and diabetes. Psychiatric disorders, substance abuse and viral co-infection were more frequent in younger patients. CONCLUSION Direct-acting antiviral therapies were well tolerated in patients older than 70 years. SVR12 rates in the elderly patient group were similar to those observed in younger patients. Differences in the prevalence of comorbidities between age groups warrant individualized attention with respect to drug-drug interactions and therapy adherence. The study was registered in the German Clinical Trials Register, DRKS-ID: DRKS00009717.
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Affiliation(s)
- Georg Dultz
- Department of Medicine 1, J.W. Goethe University Frankfurt, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany.
| | - Tobias Müller
- Charité Campus Virchow-Klinikum (CVK), Berlin, Germany
| | - Jörg Petersen
- ifi-Institute for Interdisciplinary Medicine, Hamburg, Germany
| | - Stefan Mauss
- Center for HIV and Hepatogastroenterology, Düsseldorf, Germany
| | - Tim Zimmermann
- University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Marion Muche
- Charité Campus Virchow-Klinikum (CVK), Berlin, Germany
| | | | - Thomas Berg
- University Hospital Leipzig, Leipzig, Germany
| | - Stefan Zeuzem
- Department of Medicine 1, J.W. Goethe University Frankfurt, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany
| | | | | | - Heiner Wedemeyer
- Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg Essen, Essen, Germany
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
- Leberstiftungs-GmbH Deutschland, Hannover, Germany
| | - Tania M Welzel
- Department of Medicine 1, J.W. Goethe University Frankfurt, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany
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23
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Ishikawa T, Imai M, Owaki T, Sato H, Nozawa Y, Sano T, Iwanaga A, Seki K, Honma T, Yoshida T. Successful Ombitasvir/Paritaprevir/Ritonavir Plus Ribavirin Retreatment for a Chronic Hepatitis C Genotype 2a Patient Who Relapsed after Sofosbuvir Plus Ribavirin Treatment. Intern Med 2018; 57:2843-2845. [PMID: 29780129 PMCID: PMC6207807 DOI: 10.2169/internalmedicine.0621-17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Accepted: 02/12/2018] [Indexed: 11/29/2022] Open
Abstract
The optimum retreatment strategy for chronic hepatitis C virus (HCV) patients who failed directly-acting antiviral agents (DAA)-based therapy is unknown. We herein report the outcomes of an HCV genotype (GT) 2a-infected patient with virologic failure following treatment with sofosbuvir plus ribavirin (SOF+RBV) who was successfully retreated with ombitasvir/paritaprevir/ritonavir plus ribavirin (OBV/PTV/r+RBV).
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Affiliation(s)
- Toru Ishikawa
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Japan
| | - Michitaka Imai
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Japan
| | - Takashi Owaki
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Japan
| | - Hiroki Sato
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Japan
| | - Yujiro Nozawa
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Japan
| | - Tomoe Sano
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Japan
| | - Akito Iwanaga
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Japan
| | - Keiichi Seki
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Japan
| | - Terasu Honma
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Japan
| | - Toshiaki Yoshida
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Japan
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Wei B, Ji F, Yeo YH, Ogawa E, Zou B, Stave CD, Dang S, Li Z, Furusyo N, Cheung RC, Nguyen MH. Real-world effectiveness of sofosbuvir plus ribavirin for chronic hepatitis C genotype 2 in Asia: a systematic review and meta-analysis. BMJ Open Gastroenterol 2018; 5:e000207. [PMID: 30002863 PMCID: PMC6038840 DOI: 10.1136/bmjgast-2018-000207] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Revised: 06/02/2018] [Accepted: 06/08/2018] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Sofosbuvir plus ribavirin (SOF+RBV) for 12 weeks is the standard treatment for chronic hepatitis C (CHC) genotype 2 (GT2) in most of Asia despite availability of new CHC medications. SOF-RBV real-world effectiveness has only been reported in small and/or single-centre studies. Our goal was to determine the real-world effectiveness of 12-week SOF+RBV therapy for CHC GT2 in Asia. METHODS A systematic search on PubMed and Embase was conducted through 30 June 2017. We identified full articles and conference proceedings of at least 10 adult patients with CHC GT2 treated with SOF+RBV for 12 weeks under real-world setting in Asia. RESULTS A total of 2208 patients from 13 studies were included. The pooled sustained virological response 12 weeks after the end of treatment (SVR12) was 95.8% (95% CI 94.6% to 96.9%) with non-significant heterogeneity (I2=34.4%). Anaemia (27.9%) was the most common adverse event (AE), with serious AEs in 2.0% and only 0.7% discontinued therapy prematurely. In subgroup analyses, patients with cirrhosis had 8.7% lower SVR12 than non-cirrhotic patients (P<0.0001), and treatment-experienced patients had 7.2% lower SVR12 than treatment-naïve patients (P=0.0002). Cirrhotic treatment-experienced patients had the lowest SVR12 at 84.5%. There were no significant differences in pooled SVR12 among patient subgroups: RBV dose reduction versus no dose reduction (P=0.30); hepatocellular carcinoma (HCC) versus no HCC (P=0.10); GT 2a versus 2b (P=0.86); and <65 vs ≥65 years of age (P=0.20). CONCLUSIONS SOF+RBV for 12 weeks was safe and effective for patients with CHC GT2 in Asia, although those with cirrhosis and prior treatment failure had a lower pooled SVR12 rate. TRIAL REGISTRATION NUMBER CRD42017067928.
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Affiliation(s)
- Bin Wei
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Fanpu Ji
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yee Hui Yeo
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Eiichi Ogawa
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Biyao Zou
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Christopher D Stave
- Lane Medical Library, Stanford University School of Medicine, Palo Alto, California, USA
| | - Shuangsuo Dang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zongfang Li
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Norihiro Furusyo
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Ramsey C Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
- Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
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25
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Sho T, Suda G, Nagasaka A, Yamamoto Y, Furuya K, Kumagai K, Uebayashi M, Terashita K, Kobayashi T, Tsunematsu I, Onodera M, Meguro T, Kimura M, Ito J, Umemura M, Izumi T, Kawagishi N, Ohara M, Ono Y, Nakai M, Natsuizaka M, Morikawa K, Ogawa K, Sakamoto N. Safety and efficacy of sofosbuvir and ribavirin for genotype 2 hepatitis C Japanese patients with renal dysfunction. Hepatol Res 2018; 48:529-538. [PMID: 29316051 DOI: 10.1111/hepr.13056] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Revised: 12/15/2017] [Accepted: 01/04/2018] [Indexed: 12/12/2022]
Abstract
AIM The safety and efficacy of sofosbuvir (SOF) and ribavirin (RBV) have not been well clarified in patients with renal dysfunction because clinical trials have not included such patients. We evaluated the safety and efficacy of SOF and RBV for genotype 2 hepatitis C virus (HCV)-infected patients with renal dysfunction. METHODS The study included genotype 2 HCV-infected patients who received SOF and RBV between July 2014 and May 2017. The sustained virologic response (SVR) after the treatment and safety during the therapy were evaluated according to renal function. RESULTS A total of 231 patients were included in this study. The median age was 62 years old, and 45.9% (106/231) were men. Of the 231 patients, 191 (82.8%) and 40 (17.2%) were classified as having chronic kidney disease (CKD) stages G1/2 and G3, respectively. The overall SVR rate was 97% (224/231). The SVR rates in patients with CKD stages G1, 2, G3a, and G3b were 98.1%, 98.6%, 87.9%, and 100%, respectively, and this therapy was tolerated. Multivariate analysis indicated that renal dysfunction was significantly associated with a non-SVR (odds ratio, 6.963; 95% confidence interval, 1.494-32.41; P = 0.013). The patients with renal dysfunction were older, had advanced liver fibrosis, lower baseline platelet and hemoglobin levels, and a higher rate of RBV dose reduction. CONCLUSIONS Sofosbuvir and RBV therapy is highly effective and safe for genotype 2 HCV-infected Japanese patients. However, attention should be paid to baseline renal function when SOF- and RBV-containing regimens are used for patients with renal dysfunction.
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Affiliation(s)
- Takuya Sho
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Goki Suda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | | | | | | | | | | | - Katsumi Terashita
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.,Kushiro Rosai Hospital, Hokkaido, Japan
| | - Tomoe Kobayashi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.,Tomakomai City Hospital, Hokkaido, Japan
| | | | | | | | - Megumi Kimura
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Jun Ito
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Machiko Umemura
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Takaaki Izumi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Naoki Kawagishi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Masatsugu Ohara
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Yuji Ono
- Sapporo City General Hospital, Hokkaido, Japan
| | - Masato Nakai
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Mitsuteru Natsuizaka
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Kenichi Morikawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
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26
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Liao X, Wang Y, Ye H, Li S, Chen L, Duan X. Role of interferon-stimulated genes in regulation of HCV infection and type I interferon anti-HCV activity. Future Virol 2018. [DOI: 10.2217/fvl-2017-0160] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
HCV chronically infects over 71 million people worldwide and is one of the leading causes of advanced liver diseases. Type I interferons (IFN-α/β) play critical role in host antiviral innate immunity. IFN-α/β exerts its anti-HCV effects through the activation of the JAK/STAT signaling pathway leading to the induction of a few hundred interferon-stimulated genes (ISGs). The interplay between ISG and HCV infection remains partially understood. In this review, we summarized the role of ISGs in HCV infection and interferon anti-HCV activity.
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Affiliation(s)
- Xinzhong Liao
- Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, 610052 Chengdu, PR China
| | - Yancui Wang
- Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, 610052 Chengdu, PR China
| | - Haiyan Ye
- Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, 610052 Chengdu, PR China
| | - Shilin Li
- Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, 610052 Chengdu, PR China
| | - Limin Chen
- Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, 610052 Chengdu, PR China
| | - Xiaoqiong Duan
- Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, 610052 Chengdu, PR China
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27
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Ogawa E, Furusyo N, Murata M, Toyoda K, Hayashi T, Ura K. Potential risk of HBV reactivation in patients with resolved HBV infection undergoing direct-acting antiviral treatment for HCV. Liver Int 2018; 38:76-83. [PMID: 28618152 DOI: 10.1111/liv.13496] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Accepted: 06/07/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Despite a known risk of hepatitis B virus (HBV) reactivation during direct-acting antiviral (DAA) treatment for patients with hepatitis C virus (HCV)-HBV coinfection, it remains unclear whether patients with past HBV infection are at risk for reactivation. This study evaluated the risk of HBV reactivation during treatment with sofosbuvir (SOF)-based regimens, focusing on patients with resolved HBV infection. METHODS This study analyzes the data of 183 consecutive patients treated with SOF-based regimens. From these patients, 63 with resolved HBV infection (negative for hepatitis B surface antigen [HBsAg] and undetectable HBV DNA but positive for hepatitis B core antibody) were eligible for this study. HBV reactivation was defined as a quantifiable HBV DNA level >20 IU/mL. RESULTS Among the patients antibody to HBsAg (anti-HBs) positive (10-500 mIU/mL) (n = 30), the titre of anti-HBs was significantly decreased with time, as shown by the results of repeated-measures analysis of variance (P = .0029). Overall, four patients (6.3%) with resolved HBV infection came to have detectable HBV DNA during treatment, including one who had HBV reactivation at week 4 (HBV DNA 80 IU/mL). However, none developed hepatic failure. Among four patients who had detectable HBV DNA during treatment, all were negative or had very low-titre (<20 mIU/mL) anti-HBs at baseline. CONCLUSIONS The titre of anti-HBs was significantly decreased from the early stage of DAA treatment. Chronic hepatitis C patients with resolved HBV infection and negative or very low-titre anti-HBs at baseline are at risk for having detectable HBV DNA transiently during treatment.
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Affiliation(s)
- Eiichi Ogawa
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Norihiro Furusyo
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Masayuki Murata
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Kazuhiro Toyoda
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Takeo Hayashi
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Kazuya Ura
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
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28
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Ogawa E, Furusyo N, Nomura H, Dohmen K, Higashi N, Takahashi K, Kawano A, Azuma K, Satoh T, Nakamuta M, Koyanagi T, Kato M, Shimoda S, Kajiwara E, Hayashi J. Short-term risk of hepatocellular carcinoma after hepatitis C virus eradication following direct-acting anti-viral treatment. Aliment Pharmacol Ther 2018; 47:104-113. [PMID: 29035002 DOI: 10.1111/apt.14380] [Citation(s) in RCA: 84] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2017] [Revised: 07/10/2017] [Accepted: 09/22/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND With the development of direct-acting anti-virals (DAAs), almost all patients with chronic hepatitis C virus (HCV) infection can achieve sustained viral response (SVR). AIM To evaluate the short-term risk of HCC among patients with SVR by DAAs, including those with cirrhosis or previous HCC. METHODS This large-scale, multicentre cohort study included 1,675 consecutive patients who achieved SVR by treatment with interferon-free sofosbuvir-based regimens, divided into groups with (n = 152) or without previous HCC (n = 1,523). The Kaplan-Meier method and Cox proportional hazard analysis were used to calculate the cumulative HCC incidence and related factors of HCC. RESULTS During the follow-up period (median: 17 months), 46 (2.7%) patients developed HCC. The 1-year cumulative rates of de novo HCC were 0.4% and 4.9% for the noncirrhosis and cirrhosis groups respectively (log-rank test: P < 0.001). For cirrhotic patients, serum α-fetoprotein level at the end of treatment (EOT-AFP) was the strongest predictor of de novo HCC. The 1-year cumulative de novo HCC rates were 1.4% and 13.1% in the EOT-AFP < 9.0 ng/mL and ≥ 9.0 ng/mL groups (cut-off value) respectively (log-rank test: P < 0.001). The 1-year cumulative rates of HCC recurrence were 6.5% and 23.1% for the noncirrhosis and cirrhosis groups respectively (log-rank test: P = 0.023). For cirrhotic patients, previous HCC characteristics were significantly associated with HCC recurrence. In contrast, sex, age and metabolic features did not influence de novo HCC or recurrence. CONCLUSIONS For cirrhotic patients after elimination of HCV, serum EOT-AFP level and previous HCC characteristics would be useful markers for predicting de novo HCC or recurrence.
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29
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Huang CF, Yu ML. Treating hepatitis C in the elderly: pharmacotherapeutic considerations and developments. Expert Opin Pharmacother 2017; 18:1867-1874. [PMID: 29086615 DOI: 10.1080/14656566.2017.1400010] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Accepted: 10/30/2017] [Indexed: 12/17/2022]
Abstract
The seroprevalence of hepatitis C virus (HCV) infection tends to be higher in the elderly than in younger populations. Meanwhile, age per sec is an unfavorable determinant that has an impact on liver-related outcomes. Geriatric chronic hepatitis C (CHC) patients would be viewed as a special population and have an urgent need for viral eradication. Areas covered: The antivirals for CHC have evolved from interferon (IFN)-based therapyto interferon-free DAAs. The treatment strategy, in terms of its clinical efficacy and drug safety, in the elderly is presented. Expert opinion: In the previous IFN era, the sustained virological response (SVR) rate of the elderly was lower. More unfavorable safety concerns attributing to the underlying liver disease severity and extra-hepatic presentations further compromised the treatment efficacy. In the IFN-free DAA era, data showing similar SVR rates and safety profiles between the elderly and their counterparts have been demonstrated. Notably, aging is an unfavorable factor for fibrosis regression and HCC development even after HCV eradication. The extent of the improvement of extra-hepatic manifestations in the elderly with SVR is also unclear. The long-term benefits of viral eradication by DAAs in the elderly await further explorations.
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Affiliation(s)
- Chung-Feng Huang
- a Hepatobiliary Division, Department of Internal Medicine , Kaohsiung Medical University Hospital, Kaohsiung Medical University , Kaohsiung , Taiwan
- b Faculty of Internal Medicine, School of Medicine, College of Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan
- c Department of Occupational Medicine, Kaohsiung Medical University Hospital , Kaohsiung Medical University , Kaohsiung , Taiwan
| | - Ming-Lung Yu
- a Hepatobiliary Division, Department of Internal Medicine , Kaohsiung Medical University Hospital, Kaohsiung Medical University , Kaohsiung , Taiwan
- b Faculty of Internal Medicine, School of Medicine, College of Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan
- d Institute of Biomedical Sciences , National Sun Yat-Sen University , Kaohsiung , Taiwan
- e Liver Center, Division of Gastroenterology , Massachusetts General Hospital, Harvard Medical School , Boston , MA , USA
- f College of Biological Science and Technology , National Chiao Tung University , Hsin-Chu , Taiwan
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30
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Murakawa M, Asahina Y, Nagata H, Nakagawa M, Kakinuma S, Nitta S, Kawai-Kitahata F, Otani S, Kaneko S, Miyoshi M, Tsunoda T, Asano Y, Sato A, Itsui Y, Azuma S, Nouchi T, Furumoto Y, Asano T, Chuganji Y, Tohda S, Watanabe M. ITPA gene variation and ribavirin-induced anemia in patients with genotype 2 chronic hepatitis C treated with sofosbuvir plus ribavirin. Hepatol Res 2017; 47:1212-1218. [PMID: 28128521 DOI: 10.1111/hepr.12867] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2016] [Revised: 01/16/2017] [Accepted: 01/25/2017] [Indexed: 02/08/2023]
Abstract
AIM Sofosbuvir (SOF) and ribavirin (RBV) combination therapy produces a sustained response in many patients with genotype 2 chronic hepatitis C. However, RBV-induced anemia is a troublesome side-effect that may limit this treatment. Genetic variation leading to inosine triphosphatase (ITPA) deficiency is known to protect against RBV-induced hemolytic anemia. This study aimed to evaluate the relationships between the efficacy and safety of SOF/RBV treatment and ITPA gene variants. METHODS Ninety patients with genotype 2 chronic hepatitis C treated with SOF/RBV were studied. The relationships among genetic polymorphisms of ITPA and the decline in hemoglobin levels from baseline, RBV dose reduction, and sustained virological response (SVR) rates were analyzed. RESULTS Overall SVR at 12 weeks was 94.4% (85/90). Patients with the ITPA CA/AA genotypes had a lower degree of anemia throughout the therapy than those with the ITPA CC genotype. The percentage of patients requiring RBV dose reduction was significantly lower for those with the ITPA CA/AA variation, a difference even more apparent when the pretreatment hemoglobin level was <12 g/dL. The dose reduction of RBV and serum albumin level were significantly associated with SVR. CONCLUSIONS Patients with the ITPA CA/AA genotype were less likely to develop anemia than those with the ITPA CC genotype and were more likely to complete SOF/RBV therapy. These results may provide a valuable pharmacogenetic diagnostic tool to predict drug-induced adverse events, particularly in patients with pre-existing anemia.
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Affiliation(s)
- Miyako Murakawa
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.,Department of Clinical Laboratory, Medical Hospital of Tokyo Medical and Dental University, Tokyo, Japan
| | - Yasuhiro Asahina
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.,Department for Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan
| | - Hiroko Nagata
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Mina Nakagawa
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Sei Kakinuma
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.,Department for Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan
| | - Sayuri Nitta
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Fukiko Kawai-Kitahata
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Satoshi Otani
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Shun Kaneko
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Masato Miyoshi
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Tomoyuki Tsunoda
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yu Asano
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Ayako Sato
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yasuhiro Itsui
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Seishin Azuma
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | | | | | - Tooru Asano
- Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan
| | | | - Shuji Tohda
- Department of Clinical Laboratory, Medical Hospital of Tokyo Medical and Dental University, Tokyo, Japan
| | - Mamoru Watanabe
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
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31
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Atsukawa M, Tsubota A, Kondo C, Shimada N, Abe H, Kato K, Okubo T, Arai T, Itokawa N, Iio E, Tanaka Y, Iwakiri K. Effectiveness and safety of community-based treatment with sofosbuvir plus ribavirin for elderly patients with genotype 2 chronic hepatitis C. Dig Liver Dis 2017; 49:1029-1035. [PMID: 28499694 DOI: 10.1016/j.dld.2017.04.012] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2016] [Revised: 04/17/2017] [Accepted: 04/18/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND The aim of this study was to clarify the effectiveness and safety of sofosbuvir/ribavirin therapy for elderly patients with genotype 2-infected chronic hepatitis C (CHC) in Japan. METHODS A multicenter, retrospective study evaluated the effectiveness and safety of sofosbuvir/ribavirin based on real-world clinical data. RESULTS The subjects consisted of 270 patients, 47.0% of whom were aged ≥65 years. The sustained virological response rates in patients aged <65 and ≥65 years were 98.6% and 95.3%, respectively. Hemoglobin levels decreased during treatment due to ribavirin-related hemolysis, and were significantly lower in patients aged ≥65 years than those aged <65 years at all time-points. A reduction in ribavirin dose was necessary in 31.0% (26/84) of patients with hemoglobin levels <13.0g/dL and in 70.7% (39/127) of those aged >65 years. Although the most frequent adverse event was anemia, no patients discontinued the use of either ribavirin or sofosbuvir. The incidence of ribavirin-related anemia in patients aged ≥65 years was 34.6% and significantly higher compared with that in patients aged <65 years (2.8%). CONCLUSIONS Treatment with sofosbuvir/ribavirin for genotype 2-infected CHC was effective and safe even for elderly patients, although the incidence of adverse events including ribavirin-related anemia was relatively high.
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Affiliation(s)
- Masanori Atsukawa
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
| | - Akihito Tsubota
- Core Research Facilities for Basic Science, Research Center for Medical Sciences, Jikei University School of Medicine, Tokyo, Japan
| | - Chisa Kondo
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan
| | - Noritomo Shimada
- Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Chiba, Japan
| | - Hiroshi Abe
- Department of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Matsudo, Chiba, Japan
| | - Keizo Kato
- Department of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Matsudo, Chiba, Japan
| | - Tomomi Okubo
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan
| | - Taeang Arai
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan
| | - Norio Itokawa
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan
| | - Etsuko Iio
- Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
| | - Yasuhito Tanaka
- Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
| | - Katsuhiko Iwakiri
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
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32
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Fabrizio C, Saracino A, Scudeller L, Milano E, Dell'Acqua R, Bruno G, Lo Caputo S, Monno L, Milella M, Angarano G. The elderly and direct antiviral agents: Constraint or challenge? Dig Liver Dis 2017; 49:1036-1042. [PMID: 28651903 DOI: 10.1016/j.dld.2017.05.019] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2017] [Revised: 05/16/2017] [Accepted: 05/22/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Direct antiviral agents (DAAs) for chronic hepatitis C showed great effectiveness and good safety profile. So far, few data are available about their use in elderly subjects. AIM To assess management, safety and outcome of DAAs treatments in the elderly. METHODS This retrospective, single-centre study enrolled all patients aged ≥65 years, compared by age (group A: 65-74 years, group B: ≥75 years), who completed DAAs between February 2015-November 2016. Variables potentially associated to adverse events (AEs) were analyzed. Sustained virological response (SVR) was evaluated at 12-weeks follow-up. RESULTS DAAs were administered to 221 patients aged ≥65 years (males: 112; group A: 130, group B: 91). Prescribed regimens were: sofosbuvir-based: 44 patients (19.9%), simeprevir-based: 25 (15%), ledipasvir-based: 49 (22.2%), daclatasvir-based: 12 (5.4%), paritaprevir/ritonavir+ombitasvir±dasabuvir: 91 (41.2%). Ribavirin was used in 121 patients. In 58 subjects co-medications were adjusted due to drug interactions. At least one AE occurred in 130 patients, including 13 SAEs, mainly in older subjects (p=0.04). Female sex (p=0.04), liver stiffness (p=0.023), use of simeprevir (p=0.03) and ribavirin (p=0.009) were associated with AEs. SVR-12 was achieved in 96,9% of subjects. CONCLUSIONS A careful baseline evaluation and a strict monitoring allow to optimise management and outcome of DAAs in elderly.
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Affiliation(s)
- Claudia Fabrizio
- Clinic of Infectious Diseases, University of Bari, University Hospital Policlinico, Bari, Italy.
| | - Annalisa Saracino
- Clinic of Infectious Diseases, University of Bari, University Hospital Policlinico, Bari, Italy
| | - Luigia Scudeller
- Scientific Direction, Clinical Epidemiology Unit, IRCCS San Matteo Foundation, Pavia, Italy
| | - Eugenio Milano
- Clinic of Infectious Diseases, University of Bari, University Hospital Policlinico, Bari, Italy
| | - Raffaele Dell'Acqua
- Clinic of Infectious Diseases, University of Bari, University Hospital Policlinico, Bari, Italy
| | - Giuseppe Bruno
- Clinic of Infectious Diseases, University of Bari, University Hospital Policlinico, Bari, Italy
| | - Sergio Lo Caputo
- Clinic of Infectious Diseases, University of Bari, University Hospital Policlinico, Bari, Italy
| | - Laura Monno
- Clinic of Infectious Diseases, University of Bari, University Hospital Policlinico, Bari, Italy
| | - Michele Milella
- Clinic of Infectious Diseases, University of Bari, University Hospital Policlinico, Bari, Italy
| | - Gioacchino Angarano
- Clinic of Infectious Diseases, University of Bari, University Hospital Policlinico, Bari, Italy
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NS5A resistance-associated variants undermine the effectiveness of ledipasvir and sofosbuvir for cirrhotic patients infected with HCV genotype 1b. J Gastroenterol 2017; 52:845-854. [PMID: 27913920 DOI: 10.1007/s00535-016-1290-1] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2016] [Accepted: 11/14/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND Little real-world cohort data has been reported for Asians who have received interferon-free regimens with sofosbuvir (SOF) for chronic hepatitis C virus (HCV) infection. We evaluated the effectiveness and safety in clinical practice of ledipasvir (LDV) plus SOF for Japanese patients infected with HCV genotype 1. METHODS This large, multicenter, real-world cohort study consisted of 772 patients treatment-naive or -experienced, with or without compensated cirrhosis, who were treated with LDV (90 mg)/SOF (400 mg) for a fixed 12-week duration. Direct sequence analysis of the NS5A genes (L31 and Y93) was performed at baseline. RESULTS Almost all (99.6%) were infected with HCV genotype 1b. The overall sustained virological response 12 weeks after the end of treatment (SVR12) rate was 98.8% (763/772). Multivariable logistic regression analysis extracted male (odds ratio [OR] 6.62, p = 0.024), cirrhosis (OR 20.1, p = 0.0054), and baseline NS5A resistance-associated variants (RAVs) (OR 29.3, p = 0.0018) as independently associated with treatment failure. Notably, the SVR12 rate for cirrhosis patients with baseline NS5A RAVs (87.5%, 49/56) was statistically lower than for the other groups. This tendency was found except for patients with prior daclatasvir/asunaprevir failure. All patients with treatment failure had NS5A Y93H at relapse, whether or not they had NS5A RAVs at baseline. Serious adverse effects were very rare, and discontinuation was required for only five (0.6%) patients. CONCLUSIONS LDV/SOF for HCV genotype 1b was exceptionally effective, however, NS5A RAVs undermined the virological effect for cirrhosis patients. Moreover, LDV/SOF was shown to be safe, irrespective of age or fibrosis status.
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Snyder HS, Ali B, Gonzalez HC, Nair S, Satapathy SK. Efficacy and Safety of Sofosbuvir-Based Direct Acting Antivirals for Hepatitis C in Septuagenarians and Octogenarians. J Clin Exp Hepatol 2017; 7:93-96. [PMID: 28663671 PMCID: PMC5478933 DOI: 10.1016/j.jceh.2017.03.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2016] [Accepted: 03/01/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND/AIMS Treatment of chronic hepatitis C (HCV) with newer direct acting antiviral (DAA) agents has been highly effective. Unfortunately, patients over 70 years old are underrepresented in studies. Given current recommendations to screen patients born between 1945 and 1965 for HCV, it is essential to determine the efficacy and safety of DAAs within the elderly population. This study aims to evaluate clinical outcomes of patients aged 70 years or older treated for HCV with DAAs at a single tertiary care center. METHODS We identified 25 patients aged 70 years or older who were treated for HCV with a sofosbuvir-based regimen. Baseline demographics, prior HCV treatment history, HCV treatment regimen, adverse effects, and interruption or discontinuation of therapy were collected. The primary endpoint was sustained virologic response at 12 weeks after end of treatment (SVR12). Secondary outcomes were self-reported side effects, drug interactions, and changes in medical regimen of treated patients. RESULTS All patients were genotype 1 (13 1a, 9 1b, 3 unspecified). Seventeen (68%) had cirrhosis including 1 Child's Pugh class B. Fifteen patients were treatment-naïve and 10 previously failed treatment with interferon. Seventeen patients were on ledipasvir/sofosbuvir, 4 on simeprevir/sofosbuvir/ribavirin, and 4 on simeprevir/sofosbuvir. Of 25 patients included, 96% (24/25) patients achieved SVR12. Two patients had a greater than 2 g/dL drop in hemoglobin from baseline and both were on ribavirin. Ribavirin was discontinued in 1 patient. One patient required a change in proton pump inhibitor. No patients discontinued therapy due to side effects. CONCLUSIONS Patients aged 70 years or older with genotype 1 achieved high rates of sustained virologic response with treatment with newer sofosbuvir-based DAAs without any undue adverse events.
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Affiliation(s)
- Heather S. Snyder
- Department of Pharmacy, Methodist University Hospital, 1265 Union Ave, Memphis, TN 38104, USA
- Department of Clinical Pharmacy, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USA
| | - Bilal Ali
- Department of Surgery, Methodist University Hospital Transplant Institute, 1211 Union Ave, Suite 340, Memphis, TN 38104, USA
| | - Humberto C. Gonzalez
- Department of Surgery, Methodist University Hospital Transplant Institute, 1211 Union Ave, Suite 340, Memphis, TN 38104, USA
- Department of Surgery, University of Tennessee Health Science Center, 910 Madison Ave, Suite 1002, Memphis, TN 38163, USA
| | - Satheesh Nair
- Department of Surgery, Methodist University Hospital Transplant Institute, 1211 Union Ave, Suite 340, Memphis, TN 38104, USA
- Department of Surgery, University of Tennessee Health Science Center, 910 Madison Ave, Suite 1002, Memphis, TN 38163, USA
| | - Sanjaya K. Satapathy
- Department of Surgery, Methodist University Hospital Transplant Institute, 1211 Union Ave, Suite 340, Memphis, TN 38104, USA
- Department of Surgery, University of Tennessee Health Science Center, 910 Madison Ave, Suite 1002, Memphis, TN 38163, USA
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Kanda T, Nakamura M, Yasui S, Haga Y, Tawada A, Suzuki E, Ooka Y, Takahashi K, Sasaki R, Wu S, Nakamoto S, Arai M, Imazeki F, Yokosuka O. Treatment of Real-World HCV Genotype 2-Infected Japanese Patients with Sofosbuvir plus Ribavirin. BIOLOGY 2017; 6:30. [PMID: 28486403 PMCID: PMC5485477 DOI: 10.3390/biology6020030] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/01/2017] [Revised: 05/04/2017] [Accepted: 05/06/2017] [Indexed: 12/23/2022]
Abstract
The aim of this study was to characterize the treatment response and tolerability of sofosbuvir plus ribavirin therapies in Japanese patients infected with hepatitis C virus (HCV) genotype (GT)-2. This retrospective study analyzed 114 Japanese HCV GT-2 patients treated for 12 weeks with 400 mg of sofosbuvir plus weight-based ribavirin daily. This treatment led to higher sustained virologic response at 12-weeks post-treatment (SVR12) rates in both treatment-naïve and treatment-experienced patients. The efficacy of this treatment in compensated cirrhotics was the same as that in patients with chronic hepatitis. HCV GT-2a infection and lower estimated glomerular filtration rates (eGFR) tended to be associated with SVR12. Of 114 patients, 113 completed the combination of sofosbuvir plus ribavirin for 12 weeks. Seven patients without SVR12 did not have HCV NS5B-S282 mutations. The overall SVR12 rate was 90.4% (103 of 114). More effective therapeutic options with less adverse events are desired to achieve higher SVR rates in HCV GT-2 Japanese patients.
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Affiliation(s)
- Tatsuo Kanda
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Masato Nakamura
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Shin Yasui
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Yuki Haga
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Akinobu Tawada
- Safety and Health Organization, Chiba University, 1-33 Yayoicho, Inage-ku, Chiba 263-8522, Japan.
| | - Eiichiro Suzuki
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Yoshihiko Ooka
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Koji Takahashi
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Reina Sasaki
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Shuang Wu
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Shingo Nakamoto
- Department of Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Makoto Arai
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Fumio Imazeki
- Safety and Health Organization, Chiba University, 1-33 Yayoicho, Inage-ku, Chiba 263-8522, Japan.
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
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Vukotic R, Conti F, Andreone P. Hepatitis C virus eradication in the elderly: The challenge worth a long-life elixir? J Hepatol 2017; 66:476-477. [PMID: 28012863 DOI: 10.1016/j.jhep.2016.12.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2016] [Accepted: 12/12/2016] [Indexed: 01/16/2023]
Affiliation(s)
- Ranka Vukotic
- Dipartimento di Scienze Mediche e Chirurgiche, Centro di Ricerca per lo Studio delle Epatiti, Università degli Studi di Bologna, Bologna, Italy
| | - Fabio Conti
- Dipartimento di Scienze Mediche e Chirurgiche, Centro di Ricerca per lo Studio delle Epatiti, Università degli Studi di Bologna, Bologna, Italy
| | - Pietro Andreone
- Dipartimento di Scienze Mediche e Chirurgiche, Centro di Ricerca per lo Studio delle Epatiti, Università degli Studi di Bologna, Bologna, Italy.
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Current therapy for chronic hepatitis C: The role of direct-acting antivirals. Antiviral Res 2017; 142:83-122. [PMID: 28238877 PMCID: PMC7172984 DOI: 10.1016/j.antiviral.2017.02.014] [Citation(s) in RCA: 126] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Revised: 02/07/2017] [Accepted: 02/22/2017] [Indexed: 12/12/2022]
Abstract
One of the most exciting developments in antiviral research has been the discovery of the direct-acting antivirals (DAAs) that effectively cure chronic hepatitis C virus (HCV) infections. Based on more than 100 clinical trials and real-world studies, we provide a comprehensive overview of FDA-approved therapies and newly discovered anti-HCV agents with a special focus on drug efficacy, mechanisms of action, and safety. We show that HCV drug development has advanced in multiple aspects: (i) interferon-based regimens were replaced by interferon-free regimens; (ii) genotype-specific drugs evolved to drugs for all HCV genotypes; (iii) therapies based upon multiple pills per day were simplified to a single pill per day; (iv) drug potency increased from moderate (∼60%) to high (>90%) levels of sustained virologic responses; (v) treatment durations were shortened from 48 to 12 or 8 weeks; and (vi) therapies could be administered orally regardless of prior treatment history and cirrhotic status. However, despite these remarkable achievements made in HCV drug discovery, challenges remain in the management of difficult-to-treat patients.
HCV genotype-specific drugs evolve to pan-genotypic drugs. Drug potency increases from moderate (∼60%) to high (>90%) levels of sustained virologic response. Treatment durations are shortened from a 48-week to 12-week or 8-week period. HCV therapies based upon multiple pills per day are simplified to a single pill per day. HCV therapies are administered orally regardless of prior treatment history and cirrhotic status.
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Coppola N, De Pascalis S, Messina V, Di Caprio G, Martini S, de Stefano G, Starace M, Stornaiuolo G, Stanzione M, Ascione T, Minichini C, Sangiovanni V, Zampino R, Calò F, Rinaldi L, Persico M, Federico A, Buonomo AR, Borgia G, Gaeta GB, Filippini P, Gentile I. ITPase activity modulates the severity of anaemia in HCV-related cirrhosis treated with ribavirin-containing interferon-free regimens. Antivir Ther 2017; 22:551-558. [PMID: 28165327 DOI: 10.3851/imp3134] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/30/2017] [Indexed: 10/20/2022]
Abstract
BACKGROUND To investigate the association between inosine triphosphatase (ITPase) activity and the degree of anaemia occurring during direct-acting antiviral (DAA)/ribavirin (RBV)-based therapy in patients with cirrhosis. METHODS In a multicentre, prospective study 227 patients with HCV-related cirrhosis treated with DAA and RBV were enrolled. All patients were screened for the rs1127354 and rs7270101 ITPA single nucleotide polymorphisms using direct sequencing. RESULTS 150 (66.1%) patients had normal (100%) ITPase activity, 48 (21.1%) had moderate (60%) activity and 29 (12.8%) minimal (≤30%) activity. The ITPase activity significantly influenced the haemoglobin concentration: at day 15 it was -1.248 (sd ±0.978) in the 150 patients with an ITPase activity of 100% and -0.616 (±0.862) in the 77 patients with an ITPase activity less than 100% (P<0.000), and at day 30 it was -1.941 ±1.218 versus -1.11 ±1.218 (P<0.000). The 63 patients with a severe (at least 3/dl) haemoglobin decline, compared to those without, more frequently had an ITPase activity of 100% (82.1% versus 62.8%; P=0.021), were older (mean age ±sd: 66.7 ±8.2 versus 61.4 ±9.7 years; P=0.004) and were treated with a higher ribavirin dose (13.7 ±2.1 versus 12.8 ±2.5 mg/kg/day; P=0.008). At multivariate logistic regression analysis, the ITPase activity of 100% (OR: 2.83; 95% CI: 1.12, 7.10), male gender (OR: 3.22; 95% CI: 1.35, 7.66), body mass index (OR: 1.17; 95% CI: 1.03, 1.34) and dose of ribavirin (OR: 1.22; 95% CI: 1.06, 1.47) were independent predictors of a severe decline in haemoglobin (P<0.0001). CONCLUSIONS This study suggests that the polymorphisms in the ITPA gene influence the severity of anaemia during the first month of a DAA/RBV-based treatment in HCV-related cirrhosis.
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Affiliation(s)
- Nicola Coppola
- Infectious Diseases Unit, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Naples, Italy
| | - Stefania De Pascalis
- Infectious Diseases Unit, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Naples, Italy
| | | | - Giovanni Di Caprio
- Infectious Diseases Unit, AO Caserta, Caserta, Italy
- HIV Unit, Second University of Naples, Naples, Italy
| | | | - Giorgio de Stefano
- IX Interventional Ultrasound Unit for Infectious Diseases, AORN dei Colli, P.O. Cotugno, Naples, Italy
| | - Mario Starace
- Infectious Diseases Unit, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Naples, Italy
| | - Gianfranca Stornaiuolo
- Infectious Diseases Unit, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Naples, Italy
| | - Maria Stanzione
- Infectious Diseases Unit, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Naples, Italy
| | - Tiziana Ascione
- IX Interventional Ultrasound Unit for Infectious Diseases, AORN dei Colli, P.O. Cotugno, Naples, Italy
| | - Carmine Minichini
- Infectious Diseases Unit, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Naples, Italy
| | | | - Rosa Zampino
- Internal Medicine Unit, Department of Medical Science, Second University of Naples, Naples, Italy
| | - Federica Calò
- Infectious Diseases Unit, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Naples, Italy
| | - Luca Rinaldi
- Internal Medicine Unit, Department of Medical Science, Second University of Naples, Naples, Italy
| | | | | | | | | | - Giovanni Battista Gaeta
- Infectious Diseases Unit, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Naples, Italy
| | | | - Ivan Gentile
- Infectious Diseases Unit, University Federico II, Naples, Italy
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