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Inzaule S, Easterbrook P, Latona A, Ford NP, Irving W, Matthews PC, Vitoria M, Duncombe C, Giron A, McCluskey S, Lesi O, Tchamgoue S, Halford R, Adda D, Thomson E, Dusheiko G, Jordan MR. Prevalence of Drug Resistance Associated Substitutions in Persons With Chronic Hepatitis C Infection and Virological Failure Following Initial or Re-treatment With Pan-genotypic Direct-Acting Antivirals: A Systematic Review and Meta-analysis. Clin Infect Dis 2024; 79:1437-1446. [PMID: 39361017 PMCID: PMC11650865 DOI: 10.1093/cid/ciae431] [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] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Indexed: 10/05/2024] Open
Abstract
BACKGROUND The advent of short-course, curative treatment with direct-acting antivirals (DAA) has given promise for the global elimination of hepatitis C virus (HCV) infections by 2030. Virological failure occurs in 2%-12% of persons receiving curative DAA treatment and may be presaged by pre-existing polymorphisms or result from selection of drug resistant variants during therapy. METHODS We conducted a systematic review to assess the prevalence of HCV resistance associated substitutions (RAS) among individuals with chronic hepatitis C infection who had virological failure following initial or re-treatment with pan-genotypic DAA regimens. We included 34 and 22 studies assessing RAS in people with virological failure published between January 2014 and July 2023. Pooled RAS prevalence was estimated using random-effects meta-analysis. RESULTS The pooled prevalence of RAS in people with virological failure following initial DAA treatment was 78.0% (95% confidence interval [CI]: 62.0-92.0) for sofosbuvir/velpatasvir, 81.0% (95% CI: 67.0-93.0) for sofosbuvir/daclatasvir, and 79.0% (95% CI: 70.0-87.0) for glecaprevir/pibrentasvir, with a high prevalence of resistance to the NS5A inhibitors. Among those with virological failure following re-treatment regimens, RAS were present in 93.0% (95% CI: 83.0-99.0) for sofosbuvir/velpatasvir/voxilepravir and in 100% (95% CI: 92.0-100) for glecaprevir/pibrentasvir, with resistance driven by RAS to NS5A inhibitors. DISCUSSION At least 1 RAS is present in a high proportion of the few individuals with virological failure following initial or re-treatment with pan-genotypic DAA regimens. There is a need for ongoing surveillance for DAA-associated resistance, to assess risk factors for their development and clinical impact to inform best practice strategies for re-treatment.
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Affiliation(s)
- Seth Inzaule
- Amsterdam Institute for Global Health and Development, and Department of Global Health, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Philippa Easterbrook
- HIV, Hepatitis and Sexually Transmitted Infection Department, World Health Organization, Geneva, Switzerland
| | - Ashley Latona
- Division of Geographic Medicine and Infectious Diseases,Tufts University School of Medicine, Boston, Massachusetts, USA
| | - Nathan P Ford
- HIV, Hepatitis and Sexually Transmitted Infection Department, World Health Organization, Geneva, Switzerland
| | - William Irving
- School of Life Sciences, Division of Microbiology and Infectious Diseases, The University of Nottingham, Nottingham, United Kingdom
| | | | - Marco Vitoria
- HIV, Hepatitis and Sexually Transmitted Infection Department, World Health Organization, Geneva, Switzerland
| | - Chris Duncombe
- International Association of Providers of AIDS Care, Washington, DC, USA
| | - Amalia Giron
- Independent Consultant, Guatemala city, Guatemala
| | - Suzanne McCluskey
- Division of Infectious Diseases, Havard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Olufunmilayo Lesi
- HIV, Hepatitis and Sexually Transmitted Infection Department, World Health Organization, Geneva, Switzerland
| | - Serge Tchamgoue
- Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon
| | | | | | - Emma Thomson
- Medical Research Council-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom
| | - Geoff Dusheiko
- Institute for Global Health, University College London, London, United Kingdom
| | - Michael R Jordan
- Division of Geographic Medicine and Infectious Diseases,Tufts University School of Medicine, Boston, Massachusetts, USA
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Farrag AN, Kamel AM. Efficacy of 8-week daclatasvir-sofosbuvir regimen in chronic hepatitis C: a systematic review and meta-analysis. Virol J 2024; 21:275. [PMID: 39497140 PMCID: PMC11533316 DOI: 10.1186/s12985-024-02544-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Accepted: 10/16/2024] [Indexed: 11/06/2024] Open
Abstract
BACKGROUND The high rates of the sustained virologic response 12 weeks after treatment (SVR12) in real world settings provoked the adoption of shortened courses of the costly direct-acting antivirals (DAAs) regimens. This study provides, to our knowledge, the first systematic review and meta-analysis for the efficacy of the shortened 8-week course of sofosbuvir (SOF) plus daclatasvir (DCV), the most accessible DAAs in the low-middle income countries (LMICs). METHODS We performed a proportion meta-analysis to determine a reliable rate of SVR12 by pooling all studies that evaluated the results of the 8-week regimen of DCV + SOF. In addition, we applied sensitivity analyses using two imputation paradigms: a conservative approach, and a pragmatic approach to avoid overestimating the efficacy of the 8-week regimen in studies that followed a response-guided treatment (RGT) approach. RESULTS Six studies with a total of 159 patients were included. The pooled SVR12 rate ranged from 91 to 97% in the included scenarios. The pragmatic scenario showed that the pooled SVR12 was 97% (95% confidence interval (CI) 91%; 100%) with lower variability as assessed by the prediction interval. The conservative approach revealed an SVR12 of 93% (95% CI 84%; 95%). CONCLUSION The 8-week course of 60 mg DCV with SOF provided a comparable SVR12 to the standard 12-week regimen in treatment-naïve, non-HIV co-infected patients with a minimum estimated efficacy of 90%.
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Affiliation(s)
- Ahmed N Farrag
- Clinical Pharmacy Department, College of Pharmacy, Cairo University, Cairo, 11562, Egypt.
| | - Ahmed M Kamel
- Clinical Pharmacy Department, College of Pharmacy, Cairo University, Cairo, 11562, Egypt
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Vo-Quang E, Pawlotsky JM. 'Unusual' HCV genotype subtypes: origin, distribution, sensitivity to direct-acting antiviral drugs and behaviour on antiviral treatment and retreatment. Gut 2024; 73:1570-1582. [PMID: 38782565 PMCID: PMC11347264 DOI: 10.1136/gutjnl-2024-332177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Accepted: 04/30/2024] [Indexed: 05/25/2024]
Abstract
The high genetic diversity of hepatitis C virus (HCV) has led to the emergence of eight genotypes and a large number of subtypes in limited geographical areas. Currently approved pangenotypic DAA regimens have been designed and developed to be effective against the most common subtypes (1a, 1b, 2a, 2b, 2c, 3a, 4a, 5a and 6a). However, large populations living in Africa and Asia, or who have migrated from these regions to industrialised countries, are infected with 'unusual', non-epidemic HCV subtypes, including some that are inherently resistant to currently available direct-acting antiviral (DAA) drugs due to the presence of natural polymorphisms at resistance-associated substitution positions. In this review article, we describe the origin and subsequent global spread of HCV genotypes and subtypes, the current global distribution of common and unusual HCV subtypes, the polymorphisms naturally present in the genome sequences of unusual HCV subtypes that may confer inherently reduced susceptibility to DAA drugs and the available data on the response of unusual HCV subtypes to first-line HCV therapy and retreatment. We conclude that the problem of unusual HCV subtypes that are inherently resistant to DAAs and its threat to the global efforts to eliminate viral hepatitis are largely underestimated and warrant vigorous action.
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Affiliation(s)
- Erwan Vo-Quang
- National Reference Centre for Viral Hepatitis B, C and D, Department of Virology, Hôpital Henri Mondor (AP-HP), Université Paris-Est, Créteil, France
- Institut Mondor de Recherche Biomédicale (INSERM U955), Créteil, France
- Department of Hepatology, Hôpital Henri Mondor (AP-HP), Université Paris-Est, Créteil, France
| | - Jean-Michel Pawlotsky
- National Reference Centre for Viral Hepatitis B, C and D, Department of Virology, Hôpital Henri Mondor (AP-HP), Université Paris-Est, Créteil, France
- Institut Mondor de Recherche Biomédicale (INSERM U955), Créteil, France
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Ahovègbé L, Shah R, Kpossou AR, Davis C, Niebel M, Filipe A, Goldstein E, Alassan KS, Keke R, Sehonou J, Kodjoh N, Gbedo SE, Ray S, Wilkie C, Vattipally S, Tong L, Kamba PF, Gbenoudon SJ, Gunson R, Ogwang P, Thomson EC. Hepatitis C virus diversity and treatment outcomes in Benin: a prospective cohort study. THE LANCET. MICROBE 2024; 5:697-706. [PMID: 38889738 DOI: 10.1016/s2666-5247(24)00041-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 12/22/2023] [Accepted: 02/01/2024] [Indexed: 06/20/2024]
Abstract
BACKGROUND 10 million people are chronically infected with the hepatitis C virus (HCV) in sub-Saharan Africa. The assessment of viral genotypes and treatment response in this region is necessary to achieve the WHO target of worldwide elimination of viral hepatitis by 2030. We aimed to investigate the prevalence of HCV genotypes and outcomes of treatment with direct-acting antiviral agents in Benin, a country with a national HCV seroprevalence of 4%. METHODS This prospective cohort study was conducted at two referral hospitals in Benin. Individuals were eligible for inclusion if they were seropositive for HCV and willing to consent to participation in the study; exclusion criteria were an inability to give consent or incarceration. Viraemia was confirmed by PCR. The primary outcomes were to identify HCV genotypes and measure sustained virological response rates 12 weeks after completion of treatment (SVR12) with a 12-week course of sofosbuvir-velpatasvir or sofosbuvir-ledipasvir, with or without ribavirin. We conducted phylogenetic and resistance analyses after the next-generation sequencing of samples with a cycle threshold (Ct) value of 30 or fewer cycles. The in-vitro efficacy of NS5A inhibitors was tested using a subgenomic replicon assay. FINDINGS Between June 2, 2019, and Dec 30, 2020, 148 individuals were screened for eligibility, of whom 100 were recruited prospectively to the study. Plasma samples from 79 (79%) of the 100 participants were positive for HCV by PCR. At the time of the study, 52 (66%) of 79 patients had completed treatment, with an SVR12 rate of 94% (49 of 52). 57 (72%) of 79 samples had a Ct value of 30 or fewer cycles and were suitable for whole-genome sequencing, from which we characterised 29 (51%) samples as genotype 1 and 28 (49%) as genotype 2. Three new genotype 1 subtypes (1q, 1r, and 1s) and one new genotype 2 subtype (2xa) were identified. The most commonly detected subtype was 2d (12 [21%] of 57 samples), followed by 1s (eight [14%]), 1r (five [9%]), 1b (four [7%]), 1q (three [5%]), 2xa (three [5%]), and 2b (two [3%]). 20 samples (11 genotype 2 and nine genotype 1) were unassigned new singleton lineages. 53 (93%) of 57 sequenced samples had at least two resistance-associated substitutions within the NS5A gene. Subtype 2d was associated with a lower-than-expected SVR12 rate (eight [80%] of ten patients). For one patient, with subtype 2b, treatment was not successful. INTERPRETATION This study revealed a high SVR rate in Benin among individuals treated for HCV with sofosbuvir-velpatasvir, including those with highly diverse viral genotypes. Further studies of treatment effectiveness in genotypes 2d and 2b are indicated. FUNDING Medical Research Council, Wellcome, Global Challenges Research Fund, Academy of Medical Sciences, and PHARMBIOTRAC.
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Affiliation(s)
- Lucrèce Ahovègbé
- Mbarara University of Science and Technology, Mbarara, Uganda; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK.
| | - Rajiv Shah
- MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
| | - Aboudou Raïmi Kpossou
- Clinique Universitaire d'Hépato-gastroentérologie, Centre National Hospitalier et Universitaire Hubert Koutoukou Maga, Cotonou, Benin
| | - Chris Davis
- MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
| | - Marc Niebel
- MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
| | - Ana Filipe
- MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
| | - Emily Goldstein
- West of Scotland Specialist Virology Centre, NHS Greater Glasgow and Clyde, Glasgow, UK
| | | | - René Keke
- Programme National de Lutte contre le SIDA, Cotonou, Benin
| | - Jean Sehonou
- Clinique Universitaire d'Hépato-gastroentérologie, Centre National Hospitalier et Universitaire Hubert Koutoukou Maga, Cotonou, Benin
| | - Nicolas Kodjoh
- Programme National de Lutte contre les Hépatites, Cotonou, Benin
| | | | - Surajit Ray
- School of Mathematics and Statistics, University of Glasgow, Glasgow, UK
| | - Craig Wilkie
- School of Mathematics and Statistics, University of Glasgow, Glasgow, UK
| | | | - Lily Tong
- MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
| | - Pakoyo F Kamba
- Department of Pharmacy, School of Health Sciences, Makerere University, Kampala, Uganda
| | - S Judith Gbenoudon
- Laboratory of Immunology, Infectious and Allergic Diseases, Institute of Applied Biomedical Sciences, Faculty of Sciences and Technology, University of Abomey-Calavi, Cotonou, Benin
| | - Rory Gunson
- West of Scotland Specialist Virology Centre, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Patrick Ogwang
- Mbarara University of Science and Technology, Mbarara, Uganda
| | - Emma C Thomson
- MRC-University of Glasgow Centre for Virus Research, Glasgow, UK; London School of Hygiene & Tropical Medicine, London, UK.
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Kumar N, Choudhary NS. Managing HBV and HCV Infection Pre- and Post-liver Transplant. J Clin Exp Hepatol 2024; 14:101287. [PMID: 38076445 PMCID: PMC10709521 DOI: 10.1016/j.jceh.2023.09.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Accepted: 09/19/2023] [Indexed: 03/03/2025] Open
Abstract
Hepatitis B and C are common causes of end-stage liver disease and etiologies of liver transplantation. It is important to prevent recurrence in cases of hepatitis B. Nucleos(t)ide analogs are the mainstay of HBV treatment before (in patients with decompensated cirrhosis) and after liver transplantation. After the introduction of direct-acting antivirals, the treatment of HCV has become considerably easy. In patients with advanced HCV-related cirrhosis, it is better to do transplantation first and treat them after liver transplantation. The sustained virological response rates have improved from 8 to 50% in the interferon era to 90% in the direct-acting antivirals era. In the current review, we discuss the treatment of HBV and HCV before and after liver transplantation.
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Affiliation(s)
- Naveen Kumar
- Hepatology and Gastroenterology, Narayana Hospital Delhi, India
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Graf C, D’Ambrosio R, Degasperi E, Paolucci S, Llaneras J, Vermehren J, Dultz G, Peiffer KH, Finkelmeier F, Herrmann E, Zeuzem S, Buti M, Lampertico P, Dietz J, Sarrazin C. Real-world effectiveness of voxilaprevir/velpatasvir/sofosbuvir in patients following DAA failure. JHEP Rep 2024; 6:100994. [PMID: 38357421 PMCID: PMC10865039 DOI: 10.1016/j.jhepr.2023.100994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 11/08/2023] [Accepted: 12/03/2023] [Indexed: 02/16/2024] Open
Abstract
Background & Aims Voxilaprevir/velpatasvir/sofosbuvir (VOX/VEL/SOF) is highly effective for re-treatment of direct-acting antiviral (DAA)-experienced patients with chronic HCV infection. In the present study, predictors of virologic treatment response were analyzed in an integrative analysis of three large real-world cohorts. Methods Consecutive patients re-treated with VOX/VEL/SOF after DAA failure were enrolled between 2016 and 2021 in Austria, Belgium, Germany, Italy, Spain and Switzerland. Results A total of 746 patients were included: median age was 56 (16-88) years and 77% were male. Most patients were infected with HCV genotype 1 (56%) and 3 (32%). 86% of patients carried resistance-associated substitutions in the NS3, NS5A or NS5B regions. Overall, 95.4% (683/716) of patients achieved a sustained virologic response. Treatment effectiveness was significantly affected by advanced liver disease (p <0.001), hepatocellular carcinoma (p <0.001), higher baseline ALT levels (p = 0.02), HCV genotype 3 (p <0.001), and prior VEL/SOF treatment (p = 0.01). In a multivariate analysis, only HCV genotype 3, hepatocellular carcinoma and cirrhosis turned out to be independent predictors of treatment failure. Resistance-associated substitutions, as well as the presence of rare genotypes, did not impact treatment outcome. The effectiveness of rescue therapy with glecaprevir/pibrentasvir and SOF, with or without ribavirin, for 12 to 24 weeks was found to be high (100%). Conclusions Infection with HCV genotype 3, the presence of liver cancer and cirrhosis are independently associated with failure of VOX/VEL/SOF re-treatment. It is unclear whether the addition of ribavirin and/or extension of treatment duration may be effective to avoid virologic relapse on VOX/VEL/SOF. However, rescue treatment with glecaprevir/pibrentasvir+SOF seems to be effective. Impact and implications Representative data on the effectiveness of voxilaprevir/velpatasvir/sofosbuvir (VOX/VEL/SOF) in clinical practice are still scarce and the collection of a larger number of patients with difficult-to-treat cofactors including the assessment of resistance-associated substitution profiles is required before more specific recommendations for optimal re-treatment in these patients can be given. Thus, we aimed to analyze treatment effectiveness and predictors of virologic response to VOX/VEL/SOF in an integrative analysis of three large real-word cohorts. The study results, derived from a multicenter cohort consisting of 746 patients, demonstrated that re-treatment with VOX/VEL/SOF is an effective salvage therapy associated with an overall per protocol sustained virologic response rate of 95%. Hepatocellular carcinoma onset, cirrhosis and HCV genotype 3 were identified as independent negative predictors of treatment response, whereas resistance-associated substitutions, as well as rare genotypes and chimera, did not impact sustained virologic response rates following re-treatment with VOX/VEL/SOF.
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Affiliation(s)
- Christiana Graf
- Department of Internal Medicine 1, University Hospital, Goethe University, Frankfurt, Germany
| | - Roberta D’Ambrosio
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Elisabetta Degasperi
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Stefania Paolucci
- Microbiology and Virology Department, Foundation IRCCS San Matteo, Pavia, Italy
| | - Jordi Llaneras
- Hospital Universitari Vall d’Hebron, Department of Medicine of the UAB (Universitat Autònoma de Barcelona), Spain
| | - Johannes Vermehren
- Department of Internal Medicine 1, University Hospital, Goethe University, Frankfurt, Germany
| | - Georg Dultz
- Department of Internal Medicine 1, University Hospital, Goethe University, Frankfurt, Germany
| | - Kai-Henrik Peiffer
- Department of Internal Medicine 1, University Hospital, Goethe University, Frankfurt, Germany
| | - Fabian Finkelmeier
- Department of Internal Medicine 1, University Hospital, Goethe University, Frankfurt, Germany
| | - Eva Herrmann
- Institute of Biostatistics and Mathematical Modeling, Goethe University, Frankfurt, Germany
| | - Stefan Zeuzem
- Department of Internal Medicine 1, University Hospital, Goethe University, Frankfurt, Germany
- German Center for Infection Research (DZIF), External Partner Site Frankfurt, Frankfurt, Germany
| | - Maria Buti
- Hospital Universitari Vall d’Hebron, Department of Medicine of the UAB (Universitat Autònoma de Barcelona), Spain
| | - Pietro Lampertico
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- CRC A.M. e A. Migliavacca Center of Liver Diseases, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Julia Dietz
- Department of Internal Medicine 1, University Hospital, Goethe University, Frankfurt, Germany
- German Center for Infection Research (DZIF), External Partner Site Frankfurt, Frankfurt, Germany
| | - Christoph Sarrazin
- Department of Internal Medicine 1, University Hospital, Goethe University, Frankfurt, Germany
- German Center for Infection Research (DZIF), External Partner Site Frankfurt, Frankfurt, Germany
- Medizinische Klinik II, St. Josefs-Hospital, Wiesbaden, Germany
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Alghamdi AS, Alghamdi H, Alserehi HA, Babatin MA, Alswat KA, Alghamdi M, AlQutub A, Abaalkhail F, Altraif I, Alfaleh FZ, Sanai FM. SASLT guidelines: Update in treatment of hepatitis C virus infection, 2024. Saudi J Gastroenterol 2024; 30:S1-S42. [PMID: 38167232 PMCID: PMC10856511 DOI: 10.4103/sjg.sjg_333_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 11/27/2023] [Accepted: 12/03/2023] [Indexed: 01/05/2024] Open
Abstract
ABSTRACT Hepatitis C virus (HCV) infection has been a major global health concern, with a significant impact on public health. In recent years, there have been remarkable advancements in our understanding of HCV and the development of novel therapeutic agents. The Saudi Society for the Study of Liver Disease and Transplantation formed a working group to develop HCV practice guidelines in Saudi Arabia. The methodology used to create these guidelines involved a comprehensive review of available evidence, local data, and major international practice guidelines regarding HCV management. This updated guideline encompasses critical aspects of HCV care, including screening and diagnosis, assessing the severity of liver disease, and treatment strategies. The aim of this updated guideline is to assist healthcare providers in the management of HCV in Saudi Arabia. It summarizes the latest local studies on HCV epidemiology, significant changes in virus prevalence, and the importance of universal screening, particularly among high-risk populations. Moreover, it discusses the promising potential for HCV elimination as a public health threat by 2030, driven by effective treatment and comprehensive prevention strategies. This guideline also highlights evolving recommendations for advancing disease management, including the treatment of HCV patients with decompensated cirrhosis, treatment of those who have previously failed treatment with the newer medications, management in the context of liver transplantation and hepatocellular carcinoma, and treatment for special populations.
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Affiliation(s)
- Abdullah S. Alghamdi
- Department of Medicine, Gastroenterology Unit, King Fahad Hospital, Jeddah, Saudi Arabia
| | - Hamdan Alghamdi
- Hepatology Section, Hepatobiliary Sciences and Organs Transplant Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Haleema A. Alserehi
- General Directorate of Communicable Diseases, Ministry of Health, Riyadh, Saudi Arabia
| | - Mohammed A. Babatin
- Department of Medicine, Gastroenterology Unit, King Fahad Hospital, Jeddah, Saudi Arabia
| | - Khalid A. Alswat
- Liver Disease Research Center, and Riyadh, Saudi Arabia
- College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed Alghamdi
- Department of Medicine, Division of Gastroenterology, King Fahd Military Complex, Dhahran, Saudi Arabia
| | - Adel AlQutub
- Department of Gastroenterology and Hepatology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Faisal Abaalkhail
- Department of Medicine, Section of Gastroenterology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- College of Medicine, Al Faisal University, Riyadh, Saudi Arabia
| | - Ibrahim Altraif
- Hepatology Section, Hepatobiliary Sciences and Organs Transplant Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | | | - Faisal M. Sanai
- Liver Disease Research Center, and Riyadh, Saudi Arabia
- Gastroenterology Section, Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia
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8
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Medina C, García AH, Crespo FI, Toro FI, Mayora SJ, De Sanctis JB. A Synopsis of Hepatitis C Virus Treatments and Future Perspectives. Curr Issues Mol Biol 2023; 45:8255-8276. [PMID: 37886964 PMCID: PMC10605161 DOI: 10.3390/cimb45100521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 10/10/2023] [Accepted: 10/10/2023] [Indexed: 10/28/2023] Open
Abstract
Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection with HCV can lead to liver cirrhosis or cancer. Although some immune-competent individuals can clear the virus, others develop chronic HCV disease due to viral mutations or an impaired immune response. IFNs type I and III and the signal transduction induced by them are essential for a proper antiviral effect. Research on the viral cycle and immune escape mechanisms has formed the basis of therapeutic strategies to achieve a sustained virological response (SVR). The first therapies were based on IFNα; then, IFNα plus ribavirin (IFN-RBV); and then, pegylated-IFNα-RBV (PEGIFNα-RIV) to improve cytokine pharmacokinetics. However, the maximum SVR was 60%, and several significant side effects were observed, decreasing patients' treatment adherence. The development of direct-acting antivirals (DAAs) significantly enhanced the SVR (>90%), and the compounds were able to inhibit HCV replication without significant side effects, even in paediatric populations. The management of coinfected HBV-HCV and HCV-HIV patients has also improved based on DAA and PEG-IFNα-RBV (HBV-HCV). CD4 cells are crucial for an effective antiviral response. The IFNλ3, IL28B, TNF-α, IL-10, TLR-3, and TLR-9 gene polymorphisms are involved in viral clearance, therapeutic responses, and hepatic pathologies. Future research should focus on searching for strategies to circumvent resistance-associated substitution (RAS) to DAAs, develop new therapeutic schemes for different medical conditions, including organ transplant, and develop vaccines for long-lasting cellular and humoral responses with cross-protection against different HCV genotypes. The goal is to minimise the probability of HCV infection, HCV chronicity and hepatic carcinoma.
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Affiliation(s)
- Christian Medina
- Institute of Immunology Dr. Nicolás E. Bianco C., Faculty of Medicine, Universidad Central de Venezuela, Caracas 1040, Venezuela; (C.M.); (F.I.C.); (F.I.T.); (S.J.M.)
| | - Alexis Hipólito García
- Institute of Immunology Dr. Nicolás E. Bianco C., Faculty of Medicine, Universidad Central de Venezuela, Caracas 1040, Venezuela; (C.M.); (F.I.C.); (F.I.T.); (S.J.M.)
| | - Francis Isamarg Crespo
- Institute of Immunology Dr. Nicolás E. Bianco C., Faculty of Medicine, Universidad Central de Venezuela, Caracas 1040, Venezuela; (C.M.); (F.I.C.); (F.I.T.); (S.J.M.)
| | - Félix Isidro Toro
- Institute of Immunology Dr. Nicolás E. Bianco C., Faculty of Medicine, Universidad Central de Venezuela, Caracas 1040, Venezuela; (C.M.); (F.I.C.); (F.I.T.); (S.J.M.)
| | - Soriuska José Mayora
- Institute of Immunology Dr. Nicolás E. Bianco C., Faculty of Medicine, Universidad Central de Venezuela, Caracas 1040, Venezuela; (C.M.); (F.I.C.); (F.I.T.); (S.J.M.)
| | - Juan Bautista De Sanctis
- Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, 779 00 Olomouc, Czech Republic
- The Czech Advanced Technology and Research Institute (Catrin), Palacky University, 779 00 Olomouc, Czech Republic
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Ivashkin VT, Chulanov VP, Mamonova NA, Maevskaya MV, Zharkova MS, Tikhonov IN, Bogomolov PO, Volchkova EV, Dmitriev AS, Znojko OO, Klimova EA, Kozlov KV, Kravchenko IE, Malinnikova EY, Maslennikov RV, Mikhailov MI, Novak KE, Nikitin IG, Syutkin VE, Esaulenko EV, Sheptulin AA, Shirokova EN, Yushchuk ND. Clinical Practice Guidelines of the Russian Society for the Study of the Liver, the Russian Gastroenterological Association, the National Scientific Society of Infectious Disease Specialists for the Diagnosis and Treatment of Chronic Hepatitis C. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2023; 33:84-124. [DOI: 10.22416/1382-4376-2023-33-1-84-124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/26/2024]
Abstract
Аim:diagnosis and treatment algorithms in the clinical recommendations intended for general practitioners, gastroenterologists, infectious disease specialists, hepatologists on the of chronic hepatitis C are presented.Summary.Chronic viral hepatitis C is a socially significant infection, the incidence of which in the Russian Federation remains significantly high. Over the past 10 years, great progress has been made in the treatment of hepatitis C — direct acting antiviral drugs have appeared. The spectrum of their effectiveness allows to achieve a sustained virological response in more than 90 % of cases, even in groups that were not previously considered even as candidates for therapy or were difficult to treat — patients receiving renal replacement therapy, after liver transplantation (or other organs), at the stage of decompensated liver cirrhosis, HIV co-infected, etc. Interferons are excluded from the recommendations due to their low effectiveness and a wide range of adverse events. The indications for the treatment have been expanded, namely, the fact of confirmation of viral replication. The terms of dispensary observation of patients without cirrhosis of the liver have been reduced (up to 12 weeks after the end of therapy). Also, these recommendations present approaches to active screening of hepatitis in risk groups, preventive and rehabilitation measures after the end of treatment.Conclusion.Great success has been achieved in the treatment of chronic hepatitis C. In most cases, eradication of viral HCV infection is a real task even in patients at the stage of cirrhosis of the liver, with impaired renal function, HIV co-infection, after solid organs transplantation.
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Affiliation(s)
- V. T. Ivashkin
- Sechenov First Moscow State Medical University (Sechenov University)
| | - V. P. Chulanov
- Center for Epidemiologically Significant Infectious Diseases, National Medical Research Center for Phthisiopulmonology and Infectious Diseases
| | - N. A. Mamonova
- Center for Epidemiologically Significant Infectious Diseases, National Medical Research Center for Phthisiopulmonology and Infectious Diseases
| | - M. V. Maevskaya
- Sechenov First Moscow State Medical University (Sechenov University)
| | - M. S. Zharkova
- Sechenov First Moscow State Medical University (Sechenov University)
| | - I. N. Tikhonov
- Sechenov First Moscow State Medical University (Sechenov University)
| | - P. O. Bogomolov
- M.F. Vladimirsky Moscow Regional Research Clinical Institute
| | - E. V. Volchkova
- Sechenov First Moscow State Medical University (Sechenov University)
| | - A. S. Dmitriev
- Sechenov First Moscow State Medical University (Sechenov University)
| | - O. O. Znojko
- Moscow State University of Medicine and Dentistry
| | | | | | | | - E. Yu. Malinnikova
- Department of Virology, Russian Medical Academy of Continuing Professional Education
| | - R. V. Maslennikov
- Sechenov First Moscow State Medical University (Sechenov University)
| | - M. I. Mikhailov
- North-Western State Medical University named after I.I. Mechnikov
| | | | | | - V. E. Syutkin
- Sklifosovsky Clinical and Research Institute for Emergency Medicine; Russian State Research Center — Burnazyan Federal Medical Biophysical Center
| | | | - A. A. Sheptulin
- Sechenov First Moscow State Medical University (Sechenov University)
| | - E. N. Shirokova
- Sechenov First Moscow State Medical University (Sechenov University)
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Sabry N, Kamel AM, Cordie A, Esmat G. Daclatasvir as a hepatitis C infection treatment option: an up-to-date evaluation. Expert Opin Pharmacother 2023; 24:159-170. [PMID: 36369914 DOI: 10.1080/14656566.2022.2145883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
INTRODUCTION Globally, it is estimated that 290,000 patients infected with hepatitis C virus (HCV) died from hepatitis C consequences, including cirrhosis and hepatocellular carcinoma in 2019. Although daclatasvir (DCV), combined with sofosbuvir (SOF), is effective in HCV patients, the new pan-genotypic combinations are considered by many as more cost-effective and successful in eradicating HCV infection. AREAS COVERED This review discusses the safety, efficacy, and cost-effectiveness of DCV as an HCV treatment option based on real-world studies and pharmacoeconomic evaluations. EXPERT OPINION Real-life studies suggest that SOF/DCV has acceptable sustained virological response and can be used successfully to manage HCV. Nonetheless, the use of SOF/DCV is limited by the longer treatment duration in genotype (GT)-3 patients and the need for ribavirin (RBV) in treatment-experienced patients which increases the likelihood of adverse effects. DCV is likely to remain as a therapeutic option for the management of GT-1, GT-2, and GT-4 patients in resource limited settings, while GT-3 patients are more likely to benefit from RBV-free direct-acting antiviral combinations such as SOF/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8 weeks. The introduction of generics for these new pan-genotypic drugs would likely eliminate the need for SOF/DCV in the near future.
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Affiliation(s)
- Nirmeen Sabry
- Clinical Pharmacy Department, College of Pharmacy, Cairo University, Cairo, 11562, Egypt
| | - Ahmed M Kamel
- Clinical Pharmacy Department, College of Pharmacy, Cairo University, Cairo, 11562, Egypt
| | - Ahmed Cordie
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, 11562, Egypt.,Kasr Alaini HIV and Viral Hepatitis Fighting Group, Faculty of Medicine, Cairo University, Cairo, 11562, Egypt
| | - Gamal Esmat
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, 11562, Egypt
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11
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Abulitifu Y, Lian J, Adilijiang M, Liu L, Zhao F, Qian W, Zhang Y. Effectiveness and Safety of Sofosbuvir-Velpatasvir in Patients with Cirrhosis Associated with Genotype 3 Hepatitis C Infection in Xinjiang, China. Infect Drug Resist 2022; 15:6463-6470. [PMID: 36353379 PMCID: PMC9639400 DOI: 10.2147/idr.s385071] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 10/20/2022] [Indexed: 01/24/2023] Open
Abstract
Purpose Patients with cirrhosis from genotype 3 (GT3) hepatitis C virus (HCV) infection are difficult to cure. This study investigated the effectiveness and safety of sofosbuvir-velpatasvir (SOF/VEL) with and without ribavirin (RBV) in patients with GT3 HCV-infection-related cirrhosis from Xinjiang, China. Patients and Methods This study included 33 patients with GT3 HCV infected cirrhosis, who were treated with either SOF/VEL+RBV for 12 weeks (n = 27) or SOF/VEL alone for 24 weeks (n = 6) between January 2019 and June 2021. The primary endpoint was a sustained virological response at 12 weeks (SVR12), post-treatment. Secondary endpoints included changes from baseline in Child-Pugh-Turcotte scores, clinical results, hepatic-encephalopathy status, ascites, and gastrointestinal bleeding at 12 weeks, post-treatment. Results Out of the 33 patients, 18 (54.6%) were diagnosed with GT3a, 15 (45.4%) with GT3b, 16 (48.5%) with compensated cirrhosis, and 17 (51.5%) with decompensated cirrhosis. SVR12 was 87.9% (compensated cirrhosis: 93.8%, decompensated cirrhosis: 82.4%). The Child-Pugh-Turcotte scores improved at 12 weeks (p < 0.05). Total bilirubin, albumin, and alanine transaminase levels, as well as hepatic-encephalopathy were significantly improved among patients with compensated and decompensated cirrhosis (p < 0.05). The blood cell count and serum creatinine levels did not deteriorate. Conclusion SOF/VEL, with and without RBV, was effective, safe, and well-tolerated as a treatment for GT3 HCV associated cirrhosis.
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Affiliation(s)
- Yilihamu Abulitifu
- Department of Infectious Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China
| | - Jiangshan Lian
- Department of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China
| | - Munire Adilijiang
- Department of Infectious Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China
| | - Lan Liu
- Department of Infectious Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China
| | - Fengcong Zhao
- Department of Infectious Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China
| | - Wen Qian
- Department of Infectious Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China
| | - Yongping Zhang
- Department of Infectious Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China
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12
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Rodrigues JPV, Campos GRF, Bittar C, Martinelli ADLC, Campos MSDA, Pereira LRL, Rahal P, Souza FF. Selection dynamics of HCV genotype 3 resistance-associated substitutions under direct-acting antiviral therapy pressure. Braz J Infect Dis 2022; 26:102717. [PMID: 36410397 PMCID: PMC9706524 DOI: 10.1016/j.bjid.2022.102717] [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] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 10/07/2022] [Accepted: 10/30/2022] [Indexed: 11/21/2022] Open
Abstract
The chronic hepatitis C (CHC) treatment is currently based on the use of direct-acting antivirals (DAAs), and patients infected with hepatitis C virus genotype 3 (GT3) have emerged as a more difficult-to-cure population. The NS5A inhibitor daclatasvir (DCV) and sofosbuvir (SOF), an NS5B viral polymerase inhibitor, are among the drugs that compose more effective and safer treatment regimens. The virus genetic variability is related to resistance-associated substitutions (RASs) that adversely impact DAAs effectiveness. The aims of this study were to analyze the association of NS5A and NS5B RASs and other clinical factors with DAAs regimens effectiveness in patients with GT3 CHC infection. This was a prospective cohort study performed in a Brazilian university hospital. Individuals older than 18 years with GT3 CHC treated with SOF + DCV ± ribavirin (RBV) or SOF + peginterferon (PEG) + RBV were included. Blood samples were collected at baseline and post-treatment. A total of 121 patients were included. Sustained virological response rates were 87.6% for the SOF + DCV ± RBV group and 80.0% for the SOF + PEG + RBV arm. Cirrhosis, prior treatment with interferon/PEG + RBV, and baseline NS5A RAS were associated with higher risk of treatment failure. The NS5A analysis suggested that A30K, Y93H, and RAS at site 62 were related to failure. Interestingly, a likely compensatory effect was shown between A30K and A62T. Emergence of Y93H was always associated with RAS at position 62. The RASs dynamics comprehension is an important tool to indicate more effective treatment for GT3 patients.
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Affiliation(s)
- João Paulo Vilela Rodrigues
- Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
| | | | - Cintia Bittar
- Instituto de Biociências, Letras e Ciências Exatas, Universidade Estadual Paulista, São José do Rio Preto, SP, Brasil
| | | | - Marília Silveira de Almeida Campos
- Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
| | - Leonardo Régis Leira Pereira
- Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
| | - Paula Rahal
- Instituto de Biociências, Letras e Ciências Exatas, Universidade Estadual Paulista, São José do Rio Preto, SP, Brasil
| | - Fernanda Fernandes Souza
- Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
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13
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Virus-Associated Nephropathies: A Narrative Review. Int J Mol Sci 2022; 23:ijms231912014. [PMID: 36233315 PMCID: PMC9569621 DOI: 10.3390/ijms231912014] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 09/23/2022] [Accepted: 10/06/2022] [Indexed: 12/13/2022] Open
Abstract
While most viral infections cause mild symptoms and a spontaneous favorable resolution, some can lead to severe or protracted manifestations, specifically in immunocompromised hosts. Kidney injuries related to viral infections may have multiple causes related to the infection severity, drug toxicity or direct or indirect viral-associated nephropathy. We review here the described virus-associated nephropathies in order to guide diagnosis strategies and treatments in cases of acute kidney injury (AKI) occurring concomitantly with a viral infection. The occurrence of virus-associated nephropathy depends on multiple factors: the local epidemiology of the virus, its ability to infect renal cells and the patient's underlying immune response, which varies with the state of immunosuppression. Clear comprehension of pathophysiological mechanisms associated with a summary of described direct and indirect injuries should help physicians to diagnose and treat viral associated nephropathies.
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14
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Zago D, Pozzetto I, Pacenti M, Brancaccio G, Ragolia S, Basso M, Parisi SG. Circulating Genotypes of Hepatitis C Virus in Italian Patients before and after the Application of Wider Access Criteria to HCV Treatment. Open Microbiol J 2022. [DOI: 10.2174/18742858-v16-e2205300] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Aims:
The aims of this study were to report a description of the HCV genotype distribution in adult Italians and non-Italians subjects tested in the Microbiology and Virology Unit of the Padova University Hospital from January 2016 (after about one year from the availability of DAAs) to December 2018 and to compare genotype frequencies in the 12-month period before and after the application of the wider access criteria to HCV treatment.
Background:
Hepatitis C virus (HCV) infection is a major health problem, but the availability of direct-acting antivirals (DAAs) has dramatically changed HCV disease natural history because these drugs have excellent tolerability and they can eliminate the virus in almost all treated patients.
Objective:
The objective was to describe the circulating HCV genotypes in high-income countries in order to help health authorities in the future organization of DAAs treatment strategies; this aspect is not limited to drug prescription, but it also includes the identification of infected individuals who are undiagnosed, which is the limiting step to achieve the HCV elimination goal.
Methods:
Adult patients who had HCV genotype performed from 01/01/16 to 31/12/18 in the Microbiology and Virology Unit of the Padova University Hospital were included in the study: the two 12-month periods were April 2016-March 2017 (before period, BEF) and April 2017-March 2018 (after period, AFT).
Results:
Italians were 2168 (91.2%) and non-Italians were 208 (8.8%). Italians median age was 55 years, and females were older. Italians had a lower genotype 1 (p=0.0012) and higher genotype 2 frequencies (p<0.0001) with respect to non-Italians. Most patients aged 38-67 years: Italians were more represented in class age 48-57 years (p=0.0138), 68-77 years (p=0.001) and ≥78 years (p<0.0001); subjects with genotype 3 were the youngest and those with genotype 2 the oldest. Italian patients typed in the AFT and BEF were comparable; only a lower frequency of genotype 1 males and younger age in genotype 3 were found in AFT.
Conclusion:
Italians were older with respect to non-Italians, which implies that a different age based screening program could be applied. Italian genotype 3 subjects represent a cohort to focus on for the risk of therapeutic failure. Patients tested after the extended criteria for HCV treatment were very similar to those tested before, suggesting that HCV burden in Italians is higher than expected.
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15
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Mushtaq S, Hashmi AH, Khan A, Asad Raza Kazmi SM, Manzoor S. Emergence and Persistence of Resistance-Associated Substitutions in HCV GT3 Patients Failing Direct-Acting Antivirals. Front Pharmacol 2022; 13:894460. [PMID: 35571102 PMCID: PMC9091354 DOI: 10.3389/fphar.2022.894460] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 03/28/2022] [Indexed: 11/16/2022] Open
Abstract
Background: The hepatitis C virus has a high mutation rate, which results in the emergence of resistance-associated substitutions (RASs). Despite direct-acting antivirals (DAAs) efforts to treat chronically infected HCV genotype 3 (GT3) patients, there are concerns about the emergence and persistence of RASs in DAA failures. The objective of this study was to determine the prevalence of clinically relevant RASs in HCV NS5A and NS5B regions before and after treatment to better understand the role of RASs in treatment failures. Methods: Viral RNA was extracted before and after treatment from serum samples. NS5A and NS5B regions of HCV were amplified by nested PCR, followed by Sanger sequencing. The nucleotide sequences were aligned against HCV GT3 reference sequences, and amino acid substitutions were analyzed using the geno2pheno [hcv] webserver. Results: A total of 76 patients failing DAA therapy were stratified from the cohort of 1388. RASs were detected at the baseline in 15/76 patients and at relapse in 20/76 patients with cirrhosis and previously treated with interferons. The most prevalent NS5A RAS was Y93H found in all treatment-failing patients (14/54 in DCV vs. 6/22 in VEL), followed by A62S/T and A30K. No RASs were identified in NS5B. RASs that were present at the baseline persisted through the 24-week follow-up period and were enriched with emerging RASs during the treatment. The presence of RASs may be one of the causes of treatment failures in 26.3% of patients. Amino acid substitutions were present at the baseline in most of the patients with RASs against NS5A inhibitors. Patients with the baseline Y93H and/or A30K relapse more frequently than patients harboring A62S/T. Conclusion: Treatment-failing patients harbored NS5A RASs, and the most frequent were A30K (5/20), A62S/T (20/20), and Y93H (20/20). Direct resistance testing is recommended for optimizing re-treatment strategies in treatment-failing patients.
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Affiliation(s)
- Saima Mushtaq
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan
| | | | - Amjad Khan
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan
| | | | - Sobia Manzoor
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan
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16
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Solomon SS, Wagner-Cardoso S, Smeaton L, Sowah LA, Wimbish C, Robbins G, Brates I, Scello C, Son A, Avihingsanon A, Linas B, Anthony D, Nunes EP, Kliemann DA, Supparatpinyo K, Kityo C, Tebas P, Bennet JA, Santana-Bagur J, Benson CA, Van Schalkwyk M, Cheinquer N, Naggie S, Wyles D, Sulkowski M. A minimal monitoring approach for the treatment of hepatitis C virus infection (ACTG A5360 [MINMON]): a phase 4, open-label, single-arm trial. Lancet Gastroenterol Hepatol 2022; 7:307-317. [PMID: 35026142 PMCID: PMC8920770 DOI: 10.1016/s2468-1253(21)00397-6] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 10/24/2021] [Accepted: 10/25/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Despite widespread availability of direct-acting antivirals including generic formulations, limited progress has been made in the global adoption of hepatitis C virus (HCV) treatment. Barriers to treatment scale-up include availability and access to diagnostic and monitoring tests, health-care infrastructure, and requirement for frequent visits during treatment. METHODS ACTG A5360 was a phase 4, open-label, single-arm trial across 38 sites in Brazil, South Africa, Thailand, Uganda, and the USA. Key inclusion criteria were age of 18 years or older, evidence of active HCV infection (HCV RNA >1000 IU/mL) and HCV treatment-naive; patients with compensated cirrhosis and HIV/HCV co-infection were included but their enrolment was capped. All participants received a fixed dose combination of oral sofosbuvir (400 mg) and velpatasvir (100 mg) once daily for 12 weeks. The minimal monitoring (MINMON) approach consisted of four components: (1) there was no pre-treatment genotyping; (2) the entire treatment course (84 tablets) was dispensed at entry; (3) there were no scheduled visits or laboratory monitoring; and (4) there were two points of remote contact, at week 4 for adherence and week 22, to schedule outcome assessment at week 24 (-2 weeks to +4 weeks). Participants who missed the week 24 window could return for a visit to assess treatment response any time before week 72. Unplanned visits for any reason were permissible before the week 24 visit. The primary efficacy outcome was sustained virological response (SVR), defined as HCV RNA less than the lower limit of quantification measured at least 22 weeks post-treatment initiation; the primary safety outcome was serious adverse events. The primary efficacy analysis included all participants who initiated treatment, using a missing=failure approach. The primary safety analysis included all participants who initiated treatment and had at least one post-treatment assessment. This trial is registered at ClinicalTrials.gov, NCT03512210. FINDINGS Between Oct 22, 2018, and July 19, 2019, 400 participants were enrolled across all 38 sites; 399 initiated treatment. At the SVR assessment visit, 355 (89%) of 397 participants reported taking 100% of the trial medication during the 12-week treatment period; two patients did not have any follow-up visits after the entry visit and were excluded from the safety analyses. Overall, 379 of the 399 who initiated treatment had an SVR (95·0%, 95% CI 92·4-96·7). 14 (4%) of 397 participants reported serious adverse events between treatment initiation and week 28; none were treatment related or led to treatment discontinuation or death. 15 (4%) of 399 participants had unplanned visits; none were related to treatment. INTERPRETATION In this diverse global population of people with HCV, the MINMON approach with sofosbuvir-velpatasvir treatment was safe and achieved SVR comparable to standard monitoring observed in real-world data. Coupled with innovative case finding strategies, this strategy could be crucial to the global HCV elimination agenda. FUNDING US National Institutes of Health and Gilead Sciences.
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Affiliation(s)
- Sunil S Solomon
- Johns Hopkins University School of Medicine, Baltimore, MD, USA.
| | | | - Laura Smeaton
- Harvard T H Chan School of Public Health, Boston, MA, USA
| | | | | | | | - Irena Brates
- Harvard T H Chan School of Public Health, Boston, MA, USA
| | - Christine Scello
- Frontier Science & Technology Research Foundation, Inc, Amherst, NY, USA
| | - Annie Son
- Gilead Sciences, Foster City, CA, USA
| | - Anchalee Avihingsanon
- HIV-NAT, Thai Red Cross AIDS Research Centre and TB RU, Chulalongkorn University, Bangkok, Thailand
| | | | | | | | | | | | - Cissy Kityo
- Joint Clinical Research Centre, Kampala, Uganda
| | - Pablo Tebas
- Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Jaclyn Ann Bennet
- Clinical HIV Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa
| | | | - Constance A Benson
- Department of Medicine, University of California San Diego, San Diego, CA, USA
| | - Marije Van Schalkwyk
- Family Centre for Research with Ubuntu, Stellenbosch University, Cape Town, South Africa
| | | | | | - David Wyles
- Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA
| | - Mark Sulkowski
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
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17
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The Novel Finding of Dynamic Change in eGFR Up to One Year after End of Treatment in HCV-Infected Patients Receiving Sofosbuvir and Velpatasvir. Viruses 2022; 14:v14020362. [PMID: 35215955 PMCID: PMC8880184 DOI: 10.3390/v14020362] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/03/2022] [Accepted: 02/08/2022] [Indexed: 02/06/2023] Open
Abstract
Background: The results of long-term renal evolution in HCV-infected patients using sofosbuvir and velpatasvir (SOF/VEL), with or without ribavirin (RBV), are lacking. Aims: We evaluated the renal safety for HCV-infected patients receiving SOF/VEL. Methods: Between 1 June 2019 and 6 July 2020, we included 594 HCV-infected patients receiving SOF/VEL +/− RBV for 12 weeks in Taiwan. Viral eradication rate (defined by sustained virological response at week 12 post-treatment; SVR12) and changes to renal function were considered. Results: SVR12 was achieved in 99.3% (590/594) upon per-protocol analysis. Patients saw improved hepatobiliary function and fibrosis after the start of SOF/VEL therapy. For renal function, those with baseline estimated glomerular filtration rate (eGFR) ≥ 60 (mL/min/1.73 m2) experienced transient on-treatment reduction in renal function that improved upon ending treatment, but recurrent eGFR degradation during one-year follow-up. The use of RBV (OR = 5.200, 95% CI: 1.983–13.634, p = 0.001) was a significant risk factor at SVR24, while diabetes mellitus (OR = 2.765, 95% CI: 1.104–6.922, p = 0.030) and the use of RBV (OR = 3.143, 95% CI: 1.047–9.435, p = 0.041) were identified as significant risk factors of worsening renal function at SVR48. SOF/VEL did not worsen renal function among those with stage 4–5 chronic kidney disease (CKD) who were not receiving dialysis. Conclusions: A trend of decline in eGFR at 1 year after SOF/VEL treatment was observed among diabetic patients with baseline eGFR ≥ 60 (mL/min/1.73 m2) and concomitant use of RBV. The close monitoring of renal function is warranted. Further study should be conducted in order to weigh the risks and benefit of RBV.
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18
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Cheng PN, Mo LR, Chen CT, Chen CY, Huang CF, Kuo HT, Lo CC, Tseng KC, Huang YH, Tai CM, Peng CY, Bair MJ, Chen CH, Yeh ML, Lin CL, Lin CY, Lee PL, Chong LW, Hung CH, Chang TS, Huang JF, Yang CC, Hu JT, Lin CW, Wang CC, Su WW, Hsieh TY, Lin CL, Tsai WL, Lee TH, Chen GY, Wang SJ, Chang CC, Yang SS, Wu WC, Huang CS, Chou KH, Kao CN, Tsai PC, Liu CH, Lee MH, Cheng CY, Tsai MC, Liu CJ, Dai CY, Lin HC, Kao JH, Chuang WL, Yu ML. Sofosbuvir/Velpatasvir for Hepatitis C Virus Infection: Real-World Effectiveness and Safety from a Nationwide Registry in Taiwan. Infect Dis Ther 2022; 11:485-500. [PMID: 34967920 PMCID: PMC8847492 DOI: 10.1007/s40121-021-00576-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Accepted: 11/29/2021] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Pangenotypic direct-acting antivirals are expected to cure hepatitis C virus (HCV) in more than 95% of treated patients. However, data on the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) in Taiwan are limited. This study aims to characterize the patient population in the nationwide Taiwan Association for the Study of the Liver (TASL) HCV Registry and evaluate treatment outcome in Taiwanese patients receiving SOF/VEL. METHODS This study was a retrospective-prospective, observational, multicenter, real-world analysis. Adults with chronic hepatitis C were treated with SOF/VEL 400/100 mg ± ribavirin for 12 weeks. The primary outcome was sustained virologic response 12 weeks after end of therapy (SVR12). Factors associated with not achieving SVR12 were evaluated using logistic regression and covariate analysis. Safety was also assessed. RESULTS In total, 3480 patients were included: 86.8% genotype 1/2, 2.8% genotype 3, 0.1% genotype 4/5, 9.6% genotype 6; unclassified, 0.8%; 12.2% compensated cirrhosis; 3.3% decompensated cirrhosis; and 15.8% chronic kidney disease. Overall SVR12 rate was 99.4% (genotype 1, 99.5%; genotype 2, 99.4%; genotype 3, 96.9%; genotype 4, 100%; genotype 6, 99.7%). SVR12 rates among patients with compensated cirrhosis, decompensated cirrhosis, and chronic kidney disease stages 4-5 were 99.5%, 100%, and 100%, respectively. There were 21 patients (0.6%) who did not achieve SVR12. Factors associated with failure were treatment adherence below 60%, high viral load, and genotype 3 (p < 0.001, p = 0.028, and p = 0.001, respectively). Adverse events occurred in 10% of patients; 0.6% were serious and one was related to treatment. Treatment discontinuation occurred in 0.3% of patients; none were treatment related. The estimated glomerular filtration rate remained stable throughout treatment and follow-up, regardless of baseline values and cirrhosis status. CONCLUSION SOF/VEL was highly effective and well tolerated in Taiwanese patients, irrespective of viral genotype, liver disease severity, and comorbidities.
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Affiliation(s)
- Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Lein-Ray Mo
- Division of Gastroenterology, Tainan Municipal Hospital, Tainan, Taiwan
| | - Chun-Ting Chen
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital Penghu Branch, National Defense Medical Center, Taipei, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsing-Tao Kuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan
| | - Ching-Chu Lo
- Division of Gastroenterology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chi-Ming Tai
- Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Mackay Medical College, New Taipei City, Taiwan
| | - Chien-Hung Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan City, Taiwan
| | - Ming-Lun Yeh
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chih-Lang Lin
- Department of Gastroenterology and Hepatology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan
- Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Pei-Lun Lee
- Liouying Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Lee-Won Chong
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
- School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan City, Taiwan
- Division of Hepatogastroenterology, Department of Internal Medicine, ChiaYi Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Te Sheng Chang
- Division of Hepatogastroenterology, Department of Internal Medicine, ChiaYi Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Jee-Fu Huang
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chi-Chieh Yang
- Department of Gastroenterology, Division of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan
| | - Jui-Ting Hu
- Liver Center, Cathay General Hospital, Taipei, Taiwan
| | - Chih-Wen Lin
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, and School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Chia-Chi Wang
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Wei-Wen Su
- Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua, Taiwan
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chih-Lin Lin
- Department of Gastroenterology, Taipei City Hospital, Renai Branch, Taipei, Taiwan
| | - Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Tzong-Hsi Lee
- Division of Gastroenterology and Hepatology, Far Eastern Memorial Hospital, New Taipei, Taiwan
| | - Guei-Ying Chen
- Penghu Hospital, Ministry of Health and Welfare, Penghu, Taiwan
| | - Szu-Jen Wang
- Division of Gastroenterology, Department of Internal Medicine, Yuan's General Hospital, Kaohsiung, Taiwan
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Wen-Chih Wu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | - Kwok-Hsiung Chou
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital Penghu Branch, National Defense Medical Center, Taipei, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chien-Neng Kao
- National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chen-Hua Liu
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
| | - Mei-Hsuan Lee
- Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Institute of Public Health, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chien-Yu Cheng
- Institute of Public Health, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan
| | - Ming-Chang Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Chun-Jen Liu
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
- Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Jia-Horng Kao
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Su PS, Wu SH, Chu CJ, Su CW, Lin CC, Lee SD, Wang YJ, Lee FY, Huang YH, Hou MC. Sofosbuvir-based antiviral therapy provided highly treatment efficacy, safety, and good tolerability for Taiwanese chronic hepatitis C patients with decompensated cirrhosis. J Chin Med Assoc 2022; 85:152-159. [PMID: 34759209 DOI: 10.1097/jcma.0000000000000653] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND For patients with hepatitis C virus (HCV)-related decompensated cirrhosis, poor prognosis was documented due to the development of portal hypertension-related complications and hepatocellular carcinoma. Sofosbuvir-based direct-acting antiviral agents (DAAs) has revolutionized the treatment landscape of HCV, particularly in this subpopulation. To date, real-world efficacy, tolerability, and safety profiles for Taiwanese HCV-related decompensated cirrhosis treated by DAAs have not been reported. METHODS Between December 2015 and June 2020, 50 consecutive HCV-related Child-Turcotte-Pugh (CTP) classes B or C cirrhotics treated by sofosbuvir-based DAAs (with daclatasvir: 7, with ledipasvir: 32, with velpatasvir: 10, with ledipasvir then shifted to velpatasvir: 1) were enrolled. Forty-seven (94%) patients used DAAs in combination with low-dose ribavirin. SVR12 was defined by undetectable HCV RNA (<15 IU/mL) at treatment end and 12 weeks after the completion of therapy. RESULTS The mean age of the enrolled patients was 68.1 ± 11.2 years, 18% of the patients were CTP class C, and the baseline HCV RNA level was 5.42 ± 1.2 log10 IU/mL. The genotype distribution was as follows: 1a: 3; 1b: 34; 2: 9; 6: 3; and one patient with an unclassified HCV genotype. After DAAs treatment, the rates of undetectable HCV RNA at week 4 and at the end of the treatment were 88.9% and 98.0%, respectively. Subjective adverse events were reported by 42.0% of the patients, but they were generally mild and could be relieved by medications. One patient did not finish therapy due to sepsis with multiple organ dysfunction. The overall SVR12 rate was 96.0% (CTP class B: 97.6%, CTP class C: 88.9%). A significant improvement in hepatic functional reserve was noted after successful antiviral therapy. CONCLUSION For patients with HCV-related decompensated cirrhosis, which has been considered a contraindication for interferon-based therapy, sofosbuvir-based all-oral DAAs provided high treatment efficacy, acceptable safety, and good tolerability.
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Affiliation(s)
- Pin-Shuo Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Sih-Hsien Wu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Chi-Jen Chu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Chung-Chi Lin
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Shou-Dong Lee
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan, ROC
| | - Yuan-Jen Wang
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Fa-Yauh Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
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Kouroumalis E, Voumvouraki A. Hepatitis C virus: A critical approach to who really needs treatment. World J Hepatol 2022; 14:1-44. [PMID: 35126838 PMCID: PMC8790391 DOI: 10.4254/wjh.v14.i1.1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/14/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
Introduction of effective drugs in the treatment of hepatitis C virus (HCV) infection has prompted the World Health Organization to declare a global eradication target by 2030. Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status. A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease. Huge financial resources were redirected, and the pandemic became the first priority in every country. In this review, we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection. We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination. Alcohol consumption, HIV coinfection and the presence of components of metabolic syndrome including obesity, hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liver-related morbidity and mortality of HCV. We also examined the significance of special subpopulations like people who inject drugs and males having sex with males. Finally, we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income. We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.
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Affiliation(s)
- Elias Kouroumalis
- Department of Gastroenterology, University of Crete Medical School, Heraklion 71500, Crete, Greece
| | - Argyro Voumvouraki
- First Department of Internal Medicine, AHEPA University Hospital, Thessaloniki 54621, Greece
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21
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Zhuang L, Li J, Zhang Y, Ji S, Li Y, Zhao Y, Li B, Li W, Quan M, Duan Y, Zhao H, Cheng D, Wang X, Ou W, Xing H. Real-World Effectiveness of Direct-Acting Antiviral Regimens against Hepatitis C Virus (HCV) Genotype 3 Infection: A Systematic Review and Meta-Analysis. Ann Hepatol 2022; 23:100268. [PMID: 33059055 DOI: 10.1016/j.aohep.2020.09.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 09/16/2020] [Accepted: 09/21/2020] [Indexed: 02/04/2023]
Abstract
Patients with hepatitis C virus (HCV) genotype 3 (GT3) infection are resistant to direct-acting antiviral (DAA) treatments. This study aimed to analyze the effectiveness of sofosbuvir (SOF)+daclatasvir (DCV) ± ribavirin (RBV); SOF+velpatasvir (VEL)±RBV; SOF+VEL+voxilaprevir (VOX); and glecaprevir (GLE)+pibrentasvir (PIB) in the treatment of HCV GT3-infected patients in real-world studies. Articles were identified by searching the PubMed, EMBASE, and Cochrane Library databases from January 1, 2016 to September 10, 2019. The meta-analysis was conducted to determine the sustained virologic response (SVR) rate, using R 3.6.2 software. Thirty-four studies, conducted on a total of 7328 patients from 22 countries, met the inclusion criteria. The pooled SVR rate after 12/24 weeks of treatment was 92.07% (95% CI: 90.39-93.61%) for the evaluated regimens. Also, the SVR rate was 91.17% (95% CI: 89.23-92.94%) in patients treated with SOF+DCV±RBV; 95.08% (95% CI: 90.88-98.13%) in patients treated with SOF+VEL±RBV; 84.97% (95% CI: 73.32-93.91%) in patients treated with SOF+VEL+VOX; and 98.54% (95% CI: 96.40-99.82%) in patients treated with GLE+PIB. The pooled SVR rate of the four regimens was 95.24% (95% CI: 93.50-96.75%) in non-cirrhotic patients and 89.39% (95% CI: 86.07-92.33%) in cirrhotic patients. The pooled SVR rate was 94.41% (95% CI: 92.02-96.42%) in treatment-naive patients and 87.98% (95% CI: 84.31-91.25%) in treatment-experienced patients. The SVR rate of GLE+PIB was higher than other regimens. SOF+VEL+VOX can be used as a treatment regimen following DAA treatment failure.
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Affiliation(s)
- Liwei Zhuang
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China; Peking University Ditan Teaching Hospital, Beijing, China
| | - Junnan Li
- Department of Science and Education, Beijing Ditan Hospital, Capital Medical University, Beijing, China; Peking University Ditan Teaching Hospital, Beijing, China
| | - Yu Zhang
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Shibo Ji
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yue Li
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yingying Zhao
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ben Li
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wei Li
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Min Quan
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ying Duan
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hong Zhao
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Danying Cheng
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaomei Wang
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China; Peking University Ditan Teaching Hospital, Beijing, China
| | - Weini Ou
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China; Peking University Ditan Teaching Hospital, Beijing, China
| | - Huichun Xing
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China; Peking University Ditan Teaching Hospital, Beijing, China.
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Abstract
In the 1970s, an unknown virus was suspected for documented cases of transfusion-associated hepatitis, a phenomenon called non-A, non-B hepatitis. In 1989, the infectious transmissible agent was identified and named hepatitis C virus (HCV) and, soon enough, the first diagnostic HCV antibody test was developed, which led to a dramatic decrease in new infections. Today, HCV infection remains a global health burden and a major cause of liver cirrhosis, hepatocellular carcinoma and liver transplantation. However, tremendous advances have been made over the decades, and HCV became the first curable, chronic viral infection. The introduction of direct antiviral agents revolutionized antiviral treatment, leading to viral eradication in more than 98% of all patients infected with HCV. This Perspective discusses the history of HCV research, which reads like a role model for successful translational research: starting from a clinical observation, specific therapeutic agents were developed, which finally were implemented in national and global elimination programmes.
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Affiliation(s)
- Michael P. Manns
- grid.10423.340000 0000 9529 9877Hannover Medical School, Hannover, Germany
| | - Benjamin Maasoumy
- grid.10423.340000 0000 9529 9877Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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Abstract
BACKGROUND Underdiagnosis of HCV infection may hinder the obtainment of 2030 elimination goal. OBJECTIVE To estimate the pre-DAA HCV diagnosis rate to inform future public health effort. METHODS Data were obtained from three nationwide databases (Truven Health MarketScan Research Database 2007-2014, US Census Bureau 2012-2016 and NHANES 2007-2014). HCV diagnosis was defined with either one inpatient or two outpatient HCV International Classification of Disease 9 codes, providing the number of patients with diagnosed HCV (Truven). US Census Bureau data were used for age- and sex-standardization. We derived the total (diagnosed and undiagnosed) HCV infection using the NHANES database. To determine the rate and number of undiagnosed HCV, we subtracted diagnosed HCV burden (Truven) from the total HCV burden (NHANES). RESULTS Of the 198 073 302 privately insured Americans, 1.49% (2 951 490 persons) had HCV infection. However, only 362 672 (12.29%) persons were diagnosed with HCV, leaving 2 588 818 (87.71%) undiagnosed. About two-third (68.04%) and one-third (33.04%) of diagnosed HCV patients had HCV RNA or genotype tests overall, with even lower rates for the ≥65 age group, respectively. CONCLUSION In the pre-DAA era, only 12% of insured Americans with HCV were diagnosed. While this grim statistic is expected to rise, much more effort is needed to enhance the HCV care cascade.
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Pérez-Hernández JL, Arce-Salinas CA, Lehmann-Mendoza R, Torre-Delgadillo A, Castro-Narro GE, Cerda-Reyes E, Ramos-Gómez MV, Juárez-Chavez L, Dehesa-Violante M, Muñoz-Espinoza LE, Cisneros-Garza LE, Aiza-Haddad I, Velarde-Ruiz-Velasco JA, Contreras-Omaña R, García-Casarreal N, Carmona-Castañeda A, Higuera-De la Tijera F. Sofosbuvir-velpatasvir in Mexican patients with hepatitis C: A retrospective review. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2021; 87:52-58. [PMID: 34774460 DOI: 10.1016/j.rgmxen.2021.10.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Accepted: 10/01/2020] [Indexed: 11/17/2022]
Abstract
INTRODUCTION The sofosbuvir-velpatasvir (SOF/VEL) combination is a direct-acting antiviral therapy that is authorized and available in Mexico, making the performance of a real-world multicenter study that evaluates the sustained virologic response at 12 weeks post-treatment a relevant undertaking. METHODS A retrospective review of the case records of 241 patients seen at 20 hospitals in Mexico was conducted to assess hepatitis C treatment with the SOF/VEL combination (n = 231) and the sofosbuvir/velpatasvir/ribavirin (SOF/VEL/RBV) combination (n = 10). The primary efficacy endpoint was the percentage of patients that achieved SVR at 12 weeks after the end of treatment. RESULTS Overall SVR was 98.8% (95% CI 97.35-100%). Only three patients did not achieve SVR, two of whom had cirrhosis and a history of previous treatment with peg-IFN. Of the subgroups analyzed, all the patients with HIV coinfection, three patients with genotype 3, and the patients treated with the SOF/VEL/RBV combination achieved SVR. The subgroups with the lower success rates were patients that were treatment-experienced (96.8%) and patients with F1 fibrosis (95.5%). The most frequent adverse events were fatigue, headache, and insomnia. No serious adverse events were reported. CONCLUSION Treatments with SOF/VEL and SOF/VEL/RBV were highly safe and effective, results coinciding with those of other international real-world studies.
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Affiliation(s)
- J L Pérez-Hernández
- Hospital central sur de alta Especialidad, Servicio Médico de Petróleos Mexicanos, Mexico City, Mexico.
| | - C A Arce-Salinas
- Hospital central sur de alta Especialidad, Servicio Médico de Petróleos Mexicanos, Mexico City, Mexico
| | - R Lehmann-Mendoza
- Hospital central sur de alta Especialidad, Servicio Médico de Petróleos Mexicanos, Mexico City, Mexico
| | - A Torre-Delgadillo
- Departamento de Hepatología y trasplante hepático, Instituto Nacional de Ciencias Médicas y Nutrición Salvado Zubirán, Mexico City, Mexico
| | - G E Castro-Narro
- Departamento de Hepatología y trasplante hepático, Instituto Nacional de Ciencias Médicas y Nutrición Salvado Zubirán, Mexico City, Mexico
| | - E Cerda-Reyes
- Servicio de Gastroenterología, Hospital Central Militar, Mexico City, Mexico
| | - M V Ramos-Gómez
- Servicio de Gastroenterología, Centro Médico 20 de Noviembre ISSSTE, Mexico City, Mexico
| | - L Juárez-Chavez
- Servicio de Gastroenterología, Clínica de Especialidades Churubusco ISSSTE, Mexico City, Mexico
| | - M Dehesa-Violante
- Comité científico Fundación Mexicana para la Salud Hepática Fundhepa, Mexico City, Mexico
| | - L E Muñoz-Espinoza
- Servicio de Gastroenterología, Hospital Ángeles Lomas, Mexico City, Mexico
| | - L E Cisneros-Garza
- Servicio de Gastroenterología, Hospital Civil de Guadalajara, Guadalajara, Mexico
| | - I Aiza-Haddad
- Centro de Investigación en Enfermedades Hepáticas y Gastroenterología (CIEHG), Pachuca, Mexico
| | | | - R Contreras-Omaña
- Servicio de Gastroenterología, Hospital General de México Dr. Eduardo Liceaga, Mexico City, Mexico
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Scotto R, Buonomo AR, De Pascalis S, Nerilli M, Pinchera B, Staiano L, Mercinelli S, Cattaneo L, Stanzione M, Stornaiuolo G, Martini S, Messina V, Coppola C, Coppola N, Gentile I. Changing epidemiology of patients treated with direct acting antivirals for HCV and persistently high SVR12 in an endemic area for HCV infection in Italy: real-life 'LIver Network Activity' (LINA) cohort update results. Expert Rev Gastroenterol Hepatol 2021; 15:1057-1063. [PMID: 33573411 DOI: 10.1080/17474124.2021.1890029] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
BACKGROUND Second generation direct acting antivirals (DAAs) drastically changed the landscape of chronic HCV (CHCV). Aim of this paper was to assess the effectiveness of DAAs, also looking at the demographic characteristics of subjects enrolled. RESEARCH DESIGN AND METHODS Ambispective multi-center real-life study conducted among patients with CHCV treated with DAAs in Campania Region (Southern Italy). Patient were enrolled in two cohorts according to time of enrolment. RESULTS 1,479 patients were enrolled. Patients aged ≥60 years were 74.7% in the historic cohort (953 patients) and 70.2% in the prospective cohort (526 patients. Patients aged ≥ 60 years showed a higher prevalence of genotype 1b (p<0.001) and 2 (p<0.001), while patients aged < 60 years showed a higher prevalence of genotype 1a (p<0.001), 3 (p<0.001) and 4 (p<0.05). SVR12 was 98.5% in both cohorts. SVR12 was similar among patients of the prospective cohort aged < and ≥ 60 years (99.4% vs 98.1%). SVR12 among patients with and without cirrhosis was 96.0% and 98.9%, respectively. CONCLUSIONS DAAs provide high efficacy also in harder to treat patients. The effectiveness of DAAs is leading to a shift in patients characteristics with a greater prevalence of younger subjects and persons with mild liver disease.
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Affiliation(s)
- Riccardo Scotto
- Department of Clinical Medicine and Surgery - Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
| | - Antonio Riccardo Buonomo
- Department of Clinical Medicine and Surgery - Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
| | | | - Mariagiovanna Nerilli
- Department of Clinical Medicine and Surgery - Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
| | - Biagio Pinchera
- Department of Clinical Medicine and Surgery - Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
| | - Laura Staiano
- Department of Internal Medicine - Unit of Hepatology and Interventional Ultrasonography, OORR Area Stabiese Plesso Nuovo Gragnano, Naples, Italy
| | - Simona Mercinelli
- Department of Clinical Medicine and Surgery - Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
| | - Letizia Cattaneo
- Department of Clinical Medicine and Surgery - Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
| | | | | | | | | | - Carmine Coppola
- Department of Internal Medicine - Unit of Hepatology and Interventional Ultrasonography, OORR Area Stabiese Plesso Nuovo Gragnano, Naples, Italy
| | | | - Ivan Gentile
- Department of Clinical Medicine and Surgery - Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
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Berkan-Kawińska A, Piekarska A, Janczewska E, Lorenc B, Tudrujek-Zdunek M, Tomasiewicz K, Berak H, Horban A, Zarębska-Michaluk D, Pabjan P, Buczyńska I, Pazgan-Simon M, Dybowska D, Halota W, Pawłowska M, Klapaczyński J, Mazur W, Czauż-Andrzejuk A, Socha Ł, Laurans Ł, Garlicki A, Sitko M, Jaroszewicz J, Citko J, Dobracka B, Krygier R, Białkowska-Warzecha J, Tronina O, Belica-Wdowik T, Baka-Ćwierz B, Flisiak R. Real-world effectiveness and safety of direct-acting antivirals in patients with cirrhosis and history of hepatic decompensation: Epi-Ter2 Study. Liver Int 2021; 41:1789-1801. [PMID: 33655628 DOI: 10.1111/liv.14858] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Revised: 01/30/2021] [Accepted: 02/18/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIMS The aim of this study was to assess the real-life effectiveness and safety of direct acting antivirals (DAAs) in patients with cirrhosis and history of hepatic decompensation compared to those with compensated cirrhosis. METHOD Data of patients treated with DAAs and included in the EpiTer-2 database (N = 10 152) were collected retrospectively. The primary endpoint was sustained viral response (SVR) at 12 weeks posttreatment. Patients were also evaluated in terms of liver-related adverse events and treatment modification/discontinuation. RESULTS The overall SVR rate was 91.4% in the intent to treat (ITT) analysis and 95.2% in the per-protocol (PP) analysis (P < .001). Patients with decompensated cirrhosis had lower SVR rates compared to those with compensated cirrhosis in ITT analysis (86.4% vs 92.0%, P < .001), while not in PP analysis (92.9% vs 95.5%, P > .05). Adverse events (AE) occurred 45.6% and 29.3% of patients with decompensated and compensated cirrhosis (P < .001). Patients with decompensated cirrhosis were at higher risk of death (5.4% vs 0.9%; P < .0001) or liver decompensation (21.5% vs 1.3%; P < .0001). Treatment with protease inhibitors was not associated with hepatic decompensation (P = .3). Only 82.6% of patients with decompensated cirrhosis completed DAA treatment (vs 92.8% in compensated cirrhotics; P < .0001). CONCLUSION Despite higher frequency of AE and treatment modifications, once completed, DAAs yield comparable results for patients with decompensated and compensated cirrhosis. High rate of serious adverse events in patients with advanced liver disease treated with PI may not be related to the detrimental effect of the medications, but rather to the disease itself.
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Affiliation(s)
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Lodz, Łódź, Poland
| | - Ewa Janczewska
- Medical University of Silesia, School of Public Health in Bytom, Department of Basic Medical Sciences, Bytom, Poland.,ID Clinic, Hepatology Outpatient Department, Mysłowice, Poland
| | - Beata Lorenc
- Department of Infectious Diseases, Pomeranian Center of Infectious Diseases, Medical University of Gdansk, Gdansk, Poland
| | | | | | - Hanna Berak
- Hospital for Infectious Diseases, Warsaw Medical University, Warszawa, Poland
| | - Andrzej Horban
- Hospital for Infectious Diseases, Warsaw Medical University, Warszawa, Poland
| | - Dorota Zarębska-Michaluk
- Department of Infectious Disease, Voivodeship Hospital, Jan Kochanowski University, Kielce, Poland
| | - Paweł Pabjan
- Department of Infectious Disease, Voivodeship Hospital, Jan Kochanowski University, Kielce, Poland
| | - Iwona Buczyńska
- Department of Infectious Diseases and Hepatology, Wroclaw Medical University, Wrocław, Poland
| | - Monika Pazgan-Simon
- Department of Infectious Diseases and Hepatology, Wroclaw Medical University, Wrocław, Poland
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Nicolaus Copernicus University, Bydgoszcz, Poland
| | - Waldemar Halota
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Nicolaus Copernicus University, Bydgoszcz, Poland
| | - Małgorzata Pawłowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Nicolaus Copernicus University, Bydgoszcz, Poland
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, Central Clinical Hospital of Internal Affairs and Administration, Warszawa, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Medical University of Silesia, Chorzów, Poland
| | - Agnieszka Czauż-Andrzejuk
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
| | - Łukasz Socha
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, Szczecin, Poland
| | - Łukasz Laurans
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, Szczecin, Poland.,Multidisciplinary Regional Hospital, Gorzów Wielkopolski, Poland
| | - Aleksander Garlicki
- Department of Infectious and Tropical Diseases, Collegium Medicum, Jagiellonian University, Kraków, Poland
| | - Marek Sitko
- Department of Infectious and Tropical Diseases, Collegium Medicum, Jagiellonian University, Kraków, Poland
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia in Katowice, Bytom, Poland
| | | | | | - Rafał Krygier
- NZOZ Gemini, Infectious Diseases and Hepatology Outpatient Clinic, Zychlin, Poland
| | | | - Olga Tronina
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warszawa, Poland
| | - Teresa Belica-Wdowik
- Regional Center for Diagnosis and Treatment of Viral Hepatitis and Hepatology, John Paul II Hospital, Kraków, Poland
| | - Barbara Baka-Ćwierz
- Regional Center for Diagnosis and Treatment of Viral Hepatitis and Hepatology, John Paul II Hospital, Kraków, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
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27
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Zarębska-Michaluk D, Jaroszewicz J, Parfieniuk-Kowerda A, Janczewska E, Dybowska D, Pawłowska M, Halota W, Mazur W, Lorenc B, Janocha-Litwin J, Simon K, Piekarska A, Berak H, Klapaczyński J, Stępień P, Sobala-Szczygieł B, Citko J, Socha Ł, Tudrujek-Zdunek M, Tomasiewicz K, Sitko M, Dobracka B, Krygier R, Białkowska-Warzecha J, Laurans Ł, Flisiak R. Effectiveness and Safety of Pangenotypic Regimens in the Most Difficult to Treat Population of Genotype 3 HCV Infected Cirrhotics. J Clin Med 2021; 10:jcm10153280. [PMID: 34362064 PMCID: PMC8347334 DOI: 10.3390/jcm10153280] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2021] [Revised: 07/20/2021] [Accepted: 07/22/2021] [Indexed: 12/14/2022] Open
Abstract
There is still limited data available from real-world experience studies on the pangenotypic regimens in patients with genotype (GT) 3 hepatitis C virus (HCV) infection and liver cirrhosis. The current study aimed to evaluate the efficacy and safety of pangenotypic regimens in this difficult-to-treat population. A total of 236 patients with mean age 52.3 ± 11.3 years and male predominance (72%) selected from EpiTer-2 database were included in the analysis; 72% of them were treatment-naïve. The majority of patients (55%) received the combination of sofosbuvir/velpatasvir (SOF/VEL), 71 without and 58 with ribavirin (RBV), whereas the remaining 107 individuals were assigned to glecaprevir/pibrentasvir (GLE/PIB). The effectiveness of the treatment following GLE/PIB and SOF/VEL regimens (96% and 93%) was higher compared to SOF/VEL + RBV option (79%). The univariate analysis demonstrated the significantly lower sustained virologic response in males, in patients with baseline HCV RNA ≥ 1,000,000 IU/mL, and among those who failed previous DAA-based therapy. The multivariate logistic regression analysis recognized only the male gender and presence of ascites at baseline as the independent factors of non-response to treatment. It should be emphasized that despite the availability of pangenotypic, strong therapeutic options, GT3 infected patients with cirrhosis still remain difficult-to-treat, especially those with hepatic impairment and DAA-experienced.
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Affiliation(s)
- Dorota Zarębska-Michaluk
- Department of Infectious Diseases, Jan Kochanowski University, 25-317 Kielce, Poland;
- Correspondence: ; Tel.: +48-66-244-1465; Fax: +48-41-368-2262
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia, 40-055 Katowice, Poland; (J.J.); (B.S.-S.)
| | - Anna Parfieniuk-Kowerda
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-540 Białystok, Poland; (A.P.-K.); (R.F.)
| | - Ewa Janczewska
- Department of Basic Medical Sciences, Faculty of Health Sciences in Bytom, Medical University of Silesia, 41-902 Bytom, Poland;
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Collegium Medicum, Nicolaus Copernicus University, 87-030 Bydgoszcz, Poland; (D.D.); (M.P.); (W.H.)
| | - Małgorzata Pawłowska
- Department of Infectious Diseases and Hepatology, Collegium Medicum, Nicolaus Copernicus University, 87-030 Bydgoszcz, Poland; (D.D.); (M.P.); (W.H.)
| | - Waldemar Halota
- Department of Infectious Diseases and Hepatology, Collegium Medicum, Nicolaus Copernicus University, 87-030 Bydgoszcz, Poland; (D.D.); (M.P.); (W.H.)
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Medical University of Silesia in Katowice, 41-500 Chorzów, Poland;
| | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Medical University Gdańsk, 80-214 Gdańsk, Poland;
| | - Justyna Janocha-Litwin
- Department of Infectious Diseases and Hepatology, Medical University Wrocław, 50-367 Wrocław, Poland; (J.J.-L.); (K.S.)
| | - Krzysztof Simon
- Department of Infectious Diseases and Hepatology, Medical University Wrocław, 50-367 Wrocław, Poland; (J.J.-L.); (K.S.)
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź, 90-419 Łódź, Poland;
| | - Hanna Berak
- Hospital for Infectious Diseases in Warszawa, 02-091 Warsaw, Poland;
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, 00-241 Warszawa, Poland;
| | - Piotr Stępień
- Department of Infectious Diseases, Jan Kochanowski University, 25-317 Kielce, Poland;
| | - Barbara Sobala-Szczygieł
- Department of Infectious Diseases and Hepatology, Medical University of Silesia, 40-055 Katowice, Poland; (J.J.); (B.S.-S.)
| | - Jolanta Citko
- Medical Practice of Infections, Regional Hospital, 10-561 Olsztyn, Poland;
| | - Łukasz Socha
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, 71-455 Szczecin, Poland; (Ł.S.); (Ł.L.)
| | - Magdalena Tudrujek-Zdunek
- Department of Infectious Diseases, Medical University of Lublin, 20-059 Lublin, Poland; (M.T.-Z.); (K.T.)
| | - Krzysztof Tomasiewicz
- Department of Infectious Diseases, Medical University of Lublin, 20-059 Lublin, Poland; (M.T.-Z.); (K.T.)
| | - Marek Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University, 31-088 Kraków, Poland;
| | | | - Rafał Krygier
- Outpatients Hepatology Department, State University of Applied Sciences, 62-510 Konin, Poland;
| | | | - Łukasz Laurans
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, 71-455 Szczecin, Poland; (Ł.S.); (Ł.L.)
- Multidisciplinary Regional Hospital, 66-418 Gorzów Wielkopolski, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-540 Białystok, Poland; (A.P.-K.); (R.F.)
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Is HSD17B13 Genetic Variant a Protector for Liver Dysfunction? Future Perspective as a Potential Therapeutic Target. J Pers Med 2021; 11:jpm11070619. [PMID: 34208839 PMCID: PMC8304981 DOI: 10.3390/jpm11070619] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 06/25/2021] [Accepted: 06/26/2021] [Indexed: 12/20/2022] Open
Abstract
As diet and lifestyle have changed, fatty liver disease (FLD) has become more and more prevalent. Many genetic risk factors, such as variants of PNPLA3, TM6SF2, GCKR, and MBOAT7, have previously been uncovered via genome wide association studies (GWAS) to be associated with FLD. In 2018, a genetic variant (rs72613567, T > TA) of hydroxysteroid 17-β dehydrogenase family 13 (HSD17B13) was first associated with a lower risk of developing alcoholic liver disease and non-alcoholic fatty liver disease (NAFLD) in minor allele carriers. Other HSD17B13 variants were also later linked with either lower inflammation scores among NAFLD patients or protection against NAFLD (rs6834314, A > G and rs9992651, G > A) respectively. HSD17B13 is a lipid droplet-associated protein, but its function is still ambiguous. Compared to the other genetic variants that increase risk for FLD, HSD17B13 variants serve a protective role, making this gene a potential therapeutic target. However, the mechanism by which these variants reduce the risk of developing FLD is still unclear. Because studies in cell lines and mouse models have produced conflicting results, human liver tissue modeling using induced pluripotent stem cells may be the best way to move forward and solve this mystery.
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Tang Q, Wei L, Liu X, Hu P. Sofosbuvir-Based Therapies Achieved Satisfactory Virological Response in Chinese Individuals with Genotypes 3 and 6 Infections: A Real-World Experience. Infect Drug Resist 2021; 14:2297-2307. [PMID: 34188496 PMCID: PMC8233542 DOI: 10.2147/idr.s312902] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 05/28/2021] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Previous studies have shown that sofosbuvir-based regimens yield high sustained virological response rates in patients with hepatitis C virus (HCV) infection except for genotype 3b complicated with cirrhosis. This real-world study aims to explore the efficacy and safety of sofosbuvir-based regimens in Chinese patients with genotypes 3 and 6 infections, especially the impact of ribavirin coadministration on sustained virological response in cirrhotic patients with genotype 3b infection. METHODS This is a retrospective cohort study that included 101 patients initiated on sofosbuvir-based regimens. The main endpoint of treatment was sustained virological response at posttreatment week 12 (SVR12). RESULTS Overall, the SVR12 rates were 95.0% (96/101); specifically, the rates were 100% in sofosbuvir, 88.2% in sofosbuvir+ribavirin, 100% in sofosbuvir+daclatasvir, 100% in sofosbuvir+daclatasvir+ribavirin, 95.0% in sofosbuvir/velpatasvir, and 97.1% in sofosbuvir/velpatasvir+ribavirin (p=0.534). The SVR12 rates were comparable in patients infected with genotypes 3 and 6 (93.2% versus 97.6%, p=0.339). The SVR12 rate was 93.9% in cirrhotic patients (31/33). Among those infected with genotype 3, the SVR12 rate was 91.7% (22/24); the rate was 95.0% in those with ribavirin coadministration regimens, which was numerically higher than the 75.0% in those without ribavirin. However, no statistical difference was found (p=0.312). In total, five patients failed to achieve SVR12, including 3 patients with genotype 3b infection treated with ribavirin coadministration regimens (one of them was cirrhotic), 1 cirrhotic patient with genotype 3k infection, and 1 noncirrhotic patient with genotype 6a infection. No severe adverse event occurred. CONCLUSION Real-world data show that sofosbuvir-based regimens are highly effective and safe for patients with HCV genotypes 3 and 6 infections.
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Affiliation(s)
- Qiao Tang
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Li Wei
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Xiaoqing Liu
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
| | - Peng Hu
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
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Pan S, Feng K, Huang P, Zeng Y, Ke L, Yang X, Liu J, Lin C. Efficacy and safety of danoprevir plus sofosbuvir in GT 1, 2, 3, or 6 chronic hepatitis C patients with or without cirrhosis in China. Medicine (Baltimore) 2021; 100:e26312. [PMID: 34128871 PMCID: PMC8213259 DOI: 10.1097/md.0000000000026312] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 05/08/2021] [Accepted: 05/24/2021] [Indexed: 01/04/2023] Open
Abstract
ABSTRACT All-oral direct-acting antiviral therapies are becoming the choice for hepatitis C (HCV) treatment. In this study, we aimed to evaluate the efficacy and safety of ritonavir-boosted danoprevir (DNVr) plus sofosbuvir±ribavirin on HCV genotype 1, 2, 3, or 6 in the real world in China.In this observational, prospective, multicenter cohort, we enrolled a total of 58 patients with HCV genotype 1, 2, 3, or 6 patients from July 2018 to December 2019. All patients were treated with DNVr plus sofosbuvir ± ribavirin for 12 weeks and then followed up for 12 weeks. The primary endpoint was the rate of sustained virologic response at week 12 after the end of treatment (SVR12). The secondary endpoint was virologic response rate at end-of-treatment and adverse event outcome.Of the 58 patients who were enrolled, 5.2% (n = 3) had genotype 1a; 43.1% (n = 25) had HCV genotype 1b; 17.2% (n = 10) had genotype 2a; 5.2% (n = 3) had genotype 3a; 8.6% (n = 5) had genotype 3b; and 20.7% (n = 12) had genotype 6a. The virologic response rate at end-of-treatment was 100% (58/58). The HCV-RNA results of 5 patients were absent at week 12 after treatment. Among the 53 patients, SVR12 rate achieved 100% (53/53) with DNVr plus sofosbuvir ± ribavirin treatment in patients with HCV genotype 1b, 2a, 3, and 6a. For compensated cirrhosis and noncirrhosis patients, SVR12 was 100% with DNVr plus sofosbuvir ± ribavirin treatment. No serious event was observed during the treatment and follow-up. Only 5 patients had mild adverse events.DNVr plus sofosbuvir ± ribavirin for 12 weeks provided 100% SVR12 in a broad patient population and were well tolerated, which may be a promising regimen for CHC treatment.
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Affiliation(s)
- Shufang Pan
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University
| | - Kai Feng
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University
| | - Ping Huang
- Department of Infectious Diseases, The People's Hospital of Lianjiang, Guangdong Province
| | - Yingfu Zeng
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University
| | - Liu Ke
- Liuzhou People's Hospital, Liuzhou, Guangxi
| | | | - Jing Liu
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University
| | - Chaoshuang Lin
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University
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Wong YJ, Thurairajah PH, Kumar R, Tan J, Fock KM, Law NM, Li W, Kwek A, Tan YB, Koh J, Lee ZC, Kumar LS, Teo EK, Ang TL. Efficacy and safety of sofosbuvir/velpatasvir in a real-world chronic hepatitis C genotype 3 cohort. J Gastroenterol Hepatol 2021; 36:1300-1308. [PMID: 33217040 DOI: 10.1111/jgh.15324] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Revised: 10/19/2020] [Accepted: 10/26/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIM Real-world data on sofosbuvir/velpatasvir with and without ribavirin (SOF/VEL ± RBV), particularly among patients with genotype 3 (GT3) decompensated cirrhosis, prior treatment, coinfection, and hepatocellular carcinoma (HCC), are scarce. We aimed to assess the efficacy and safety of SOF/VEL ± RBV in a real-world setting that included both community and incarcerated GT3 hepatitis C virus (HCV) patients. METHODS We included all GT3 HCV patients treated with SOF/VEL ± RBV in our institution. The primary outcome measure was the overall sustained virological response 12 weeks after treatment (SVR12), reported in both intention-to-treat (ITT) and per-protocol analyses. The secondary outcome measures were SVR12 stratified by the presence of decompensated cirrhosis, prior treatment, HCC, and HIV/hepatitis C virus coinfection and the occurrence rate of serious adverse events requiring treatment cessation or hospitalization. RESULTS A total of 779 HCV patients were treated with 12 weeks of SOF/VEL ± RBV, of which 85% were treated during incarceration. Among the 530 GT3 HCV patients, 31% had liver cirrhosis, and 6% were treatment-experienced. The overall SVR12 for GT3 was 98.7% (95% confidence interval: 97.3%, 99.5%) and 99.2% (95% confidence interval: 98.1%, 99.8%) in ITT and per-protocol analyses, respectively. High SVR12 was also seen in ITT analysis among GT3 HCV patients with decompensated cirrhosis (88%), prior treatment (100%), HCC (100%), and HIV/hepatitis B virus coinfection (100%). Apart from one patient who developed myositis, no other serious adverse events were observed. CONCLUSION The SOF/VEL ± RBV is a safe and efficacious treatment option for GT3 HCV patients in a real-world setting. SOF/VEL with RBV may be considered for decompensated GT3 HCV patients.
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Affiliation(s)
- Yu Jun Wong
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Prem Harichander Thurairajah
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, National University of Singapore, Singapore
| | - Rahul Kumar
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Jessica Tan
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Kwong Ming Fock
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Ngai Moh Law
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Weiquan Li
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Andrew Kwek
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Yu Bin Tan
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Jingyun Koh
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Zheng Cong Lee
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | | | - Eng Kiong Teo
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Tiing-Leong Ang
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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A Two-Year Outcome Evaluation of Government-Led Initiative to Upscale Hospital-based Hepatitis C Treatment Using a Standard Two-Drug Regimen in Malaysia. HEPATITIS MONTHLY 2021. [DOI: 10.5812/hepatmon.113226] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Background: Malaysia has been fully committed to the global endeavor to eliminate hepatitis C virus (HCV) infection by 2030. In early 2018, the Ministry of Health (MOH) embarked on a “one-size-fits-all strategy” by introducing generic versions of sofosbuvir and daclatasvir as the standard treatment for HCV infection in public hospitals nationwide. Objectives: To evaluate the outcomes of such an initiative in multiple aspects, including the number and characteristics of patients treated, the extent of evidence-based drug use, the treatment completion status, individual responses to treatment, common side effects of treatment, and its economic implications. Methods: The findings were generated from the data compiled by the MOH, capturing the information regarding the treatment provided to adult HCV-infected patients in 16 selected hospitals between April 2018 and March 2020, along with the drug costs incurred. Results: A total of 1,797 patients were treated, nearly four times more than the patients receiving interferon-based treatment across the country in the preceding two years. Approximately one-third of them had liver cirrhosis, and the main HCV genotypes were 3 (46.9%) and 1a (20.0%). Dosing, treatment duration and the addition of ribavirin to the treatment generally agreed with the recommendations of the MOH. More than 90% of the patients completed the treatment course, and a sustained virologic response (SVR) rate of 95.4% (95% CI: 94.2, 96.7%) was recorded in those with a known treatment outcome (n = 1,163). The SVR achievement did not vary across HCV genotypes and cirrhosis status, but those ≥ 50 years of age (adjusted OR: 2.13; 95% CI: 1.16, 3.92) were more likely to fail the treatment. Side effects were rare. Anemia and fatigue caused treatment discontinuation in only 0.3% of the patients. The total drug expenditure reached US$678,258.20, and the mean cost of a 12-week treatment course of sofosbuvir and daclatasvir (US$235.16) was lower than the cost expected by the MOH (US$300). Conclusions: The findings demonstrate a high degree of real-world effectiveness, safety, and affordability of the standard treatment, suggesting that such a government-led initiative was reasonable and timely and could be extended to include more public health institutions.
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Cheng TS, Liang PC, Huang CF, Yeh ML, Huang CI, Lin ZY, Chen SC, Huang JF, Dai CY, Hsieh PH, Chuang WL, Yu ML. Real-world effectiveness of direct-acting antiviral agents for chronic hepatitis C patients with genotype-2 infection after completed treatment. Kaohsiung J Med Sci 2021; 37:334-345. [PMID: 33151016 DOI: 10.1002/kjm2.12315] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 09/12/2020] [Accepted: 09/23/2020] [Indexed: 12/12/2022] Open
Abstract
Chronic hepatitis C (CHC) is a major cause of cirrhosis, hepatocellular carcinoma (HCC), and mortality. Eliminating hepatitis C virus (HCV) can greatly improve long-term outcomes. Several direct-acting antiviral agents (DAAs), including sofosbuvir (SOF) plus different NS5A inhibitors, as well as non-SOF-based DAAs, including glecaprevir/pibrentasvir (GLE/PIB), have been approved for treating CHC genotype-2 (GT-2) patients in Taiwan. However, there is limited real-world effectiveness data regarding these different regimens. Thus, we aimed to evaluate the real-world efficacy in CHC GT-2 patients who underwent these DAA regimens. We retrospectively enrolled CHC GT-2 patients who were treated with SOF-based DAAs or GLE/PIB at a single medical center. A total of 704 enrolled patients were treated with either SOF + ribavirin (RBV), SOF/daclatasvir (DCV) ± RBV, SOF/ledipasvir (LDV) ± RBV, SOF/velpatasvir (VEL) ± RBV, or with GLE/PIB. The overall sustained virological response (SVR) rate was 97.9%. The SVR rate was significantly lower in the SOF + RBV group (95.6%) than in the non-SOF + RBV (98.9%) group, especially compared to the SOF/DCV (100%) and GLE/PIB groups (99.5%). Among patients treated with SOF + RBV, cirrhotic patients had significantly lower SVR rates than noncirrhotic patients (89.4% vs 98.2%). Multivariate analysis showed that patients with a younger age, hepatitis B virus coinfection, baseline cirrhosis, or those who received SOF + RBV were less likely to achieve SVR. In conclusion, for CHC GT-2 patients, SOF in combination with DCV, LDV, or VEL, as well as GLE/PIB, achieved similar high efficacies, regardless of cirrhosis, treatment experience, or chronic kidney disease status. Therefore, the use of DAA therapy to eradicate HCV should not be delayed in these populations.
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Affiliation(s)
- Tzu-Sheng Cheng
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan
- Department of Chemistry, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Ping-Hsin Hsieh
- Department of Internal Medicine, Chi Mei Hospital, Liouying, Tainan, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan
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Zarębska-Michaluk D. Genotype 3-hepatitis C virus’ last line of defense. World J Gastroenterol 2021; 27:1006-1021. [PMID: 33776369 PMCID: PMC7985731 DOI: 10.3748/wjg.v27.i11.1006] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 01/24/2021] [Accepted: 03/01/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic infection with hepatitis C virus (HCV) is one of the leading causes of liver disease globally, affecting approximately 71 million people. The majority of them are infected with genotype (GT) 1 but infections with GT3 are second in frequency. For many years, GT3 was considered to be less pathogenic compared to other GTs in the HCV family due to its favorable response to interferon (IFN)-based regimen. However, the growing evidence of a higher rate of steatosis, more rapid progression of liver fibrosis, and lower efficacy of antiviral treatment compared to infection with other HCV GTs has changed this conviction. This review presents the specifics of the course of GT3 infection and the development of therapeutic options for GT3-infected patients in the era of direct-acting antivirals (DAA). The way from a standard of care therapy with pegylated IFN-alpha (pegIFNα) and ribavirin (RBV) through a triple combination of pegIFNα + RBV and DAA to the highly potent IFN-free pangenotypic DAA regimens is discussed along with some treatment options which appeared to be dead ends. Although the implementation of highly effective pangenotypic regimens is the most recent stage of revolution in the treatment of GT3 infection, there is still room for improvement, especially in patients with liver cirrhosis and those who fail to respond to DAA therapies, particularly those containing inhibitors of HCV nonstructural protein 5A.
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Affiliation(s)
- Dorota Zarębska-Michaluk
- Department of Infectious Diseases, Jan Kochanowski University, Kielce 25-369, Świętokrzyskie, Poland
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Goldberg D, Ross-Driscoll K, Lynch R. County Differences in Liver Mortality in the United States: Impact of Sociodemographics, Disease Risk Factors, and Access to Care. Gastroenterology 2021; 160:1140-1150.e1. [PMID: 33220253 PMCID: PMC8650724 DOI: 10.1053/j.gastro.2020.11.016] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 11/05/2020] [Accepted: 11/10/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Data have demonstrated state-wide variability in mortality rates from liver disease (cirrhosis + hepatocellular carcinoma), but data are lacking at the local level (eg, county) to identify factors associated with variability in liver disease-related mortality and hotspots of liver disease mortality. METHODS We used Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research data from 2009 to 2018 to calculate county-level, age-adjusted liver disease-related death rates. We fit multivariable linear regression models to adjust for county-level covariates related to demographics (ie, race and ethnicity), medical comorbidities (eg, obesity), access to care (eg, uninsured rate), and geographic (eg, distance to closest liver transplant center) variables. We used optimized hotspot analysis to identify clusters of liver disease mortality hotspots based on the final multivariable models. RESULTS In multivariable models, 61% of the variability in among-county mortality was explained by county-level race/ethnicity, poverty, uninsured rates, distance to the closest transplant center, and local rates of obesity, diabetes, and alcohol use. Despite adjustment, significant within-state variability in county-level mortality rates was found. Of counties in the top fifth percentile (ie, highest mortality) of fully adjusted mortality, 60% were located in 3 states: Oklahoma, Texas, and New Mexico. Adjusted mortality rates were highly spatially correlated, representing 5 clusters: South Florida; Appalachia and the eastern part of the Midwest; Texas and Oklahoma; New Mexico, Arizona, California, and southern Oregon; and parts of Washington and Montana. CONCLUSIONS Our data demonstrate significant intrastate differences in liver disease-related mortality, with more than 60% of the variability explained by patient demographics, clinical risk factors for liver disease, and access to specialty liver care.
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Affiliation(s)
- David Goldberg
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
| | - Katherine Ross-Driscoll
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia; Division of Transplantation, Department of Surgery, Emory University School of Medicine, Atlanta, Georgia
| | - Raymond Lynch
- Division of Transplantation, Department of Surgery, Emory University School of Medicine, Atlanta, Georgia
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Pérez-Hernández JL, Arce-Salinas CA, Lehmann-Mendoza R, Torre-Delgadillo A, Castro-Narro GE, Cerda-Reyes E, Ramos-Gómez MV, Juárez-Chavez L, Dehesa-Violante M, Muñoz-Espinosa LE, Cisneros-Garza LE, Aiza-Haddad I, Velarde-Ruiz-Velasco JA, Contreras-Omaña R, García-Casarreal N, Carmona-Castañeda A, Higuera-De la Tijera F. Sofosbuvir-velpatasvir in Mexican patients with hepatitis C: A retrospective review. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2021; 87:S0375-0906(20)30156-7. [PMID: 33531165 DOI: 10.1016/j.rgmx.2020.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 09/21/2020] [Accepted: 10/01/2020] [Indexed: 06/12/2023]
Abstract
INTRODUCTION The sofosbuvir-velpatasvir (SOF/VEL) combination is a direct-acting antiviral therapy that is authorized and available in Mexico, making the performance of a real-world multicenter study that evaluates the sustained virologic response at 12 weeks post-treatment a relevant undertaking. METHODS A retrospective review of the case records of 241 patients seen at 20 hospitals in Mexico was conducted to assess hepatitis C treatment with the SOF/VEL combination (n = 231) and the sofosbuvir/velpatasvir/ribavirin (SOF/VEL/RBV) combination (n = 10). The primary efficacy endpoint was the percentage of patients that achieved SVR at 12 weeks after the end of treatment. RESULTS Overall SVR was 98.8% (95% CI 97.35-100%). Only three patients did not achieve SVR, two of whom had cirrhosis and a history of previous treatment with peg-IFN. Of the subgroups analyzed, all the patients with HIV coinfection, three patients with genotype 3, and the patients treated with the SOF/VEL/RBV combination achieved SVR. The subgroups with the lower success rates were patients that were treatment-experienced (96.8%) and patients with F1 fibrosis (95.5%). The most frequent adverse events were fatigue, headache, and insomnia. No serious adverse events were reported. CONCLUSION Treatments with SOF/VEL and SOF/VEL/RBV were highly safe and effective, results coinciding with those of other international real-world studies.
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Affiliation(s)
- J L Pérez-Hernández
- Hospital central sur de alta Especialidad, Servicio Médico de Petróleos Mexicanos, Ciudad de México, México.
| | - C A Arce-Salinas
- Hospital central sur de alta Especialidad, Servicio Médico de Petróleos Mexicanos, Ciudad de México, México
| | - R Lehmann-Mendoza
- Hospital central sur de alta Especialidad, Servicio Médico de Petróleos Mexicanos, Ciudad de México, México
| | - A Torre-Delgadillo
- Departamento de Hepatología y trasplante hepático, Instituto Nacional de Ciencias Médicas y Nutrición Salvado Zubirán, Ciudad de México, México
| | - G E Castro-Narro
- Departamento de Hepatología y trasplante hepático, Instituto Nacional de Ciencias Médicas y Nutrición Salvado Zubirán, Ciudad de México, México
| | - E Cerda-Reyes
- Servicio de Gastroenterología, Hospital Central Militar, Ciudad de México, México
| | - M V Ramos-Gómez
- Servicio de Gastroenterología, Centro Médico 20 de Noviembre ISSSTE, Ciudad de México, México
| | - L Juárez-Chavez
- Servicio de Gastroenterología, Clínica de Especialidades Churubusco ISSSTE, Ciudad de México, México
| | - M Dehesa-Violante
- Comité científico Fundación Mexicana para la Salud Hepática Fundhepa, Ciudad de México, México
| | - L E Muñoz-Espinosa
- Hospital universitario José Eleuterio González de la UANL, Monterrey, NL, México
| | - L E Cisneros-Garza
- Centro de Enfermedades Hepáticas,Hospital San José Tec de Monterrey, Monterrey, NL, México
| | - I Aiza-Haddad
- Servicio de Gastroenterología, Hospital Ángeles Lomas, Ciudad de México, México
| | | | - R Contreras-Omaña
- Centro de Investigación en Enfermedades Hepáticas y Gastroenterología (CIEHG), Pachuca, México
| | | | | | - F Higuera-De la Tijera
- Servicio de Gastroenterología, Hospital General de México Dr. Eduardo Liceaga, Ciudad de México, México
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Mushtaq S, Mansoor A, Umar M, Khan A, Siddiqi S, Manzoor S. Direct-acting antiviral agents in the treatment of chronic hepatitis C-Real-life experience from clinical practices in Pakistan. J Med Virol 2020; 92:3475-3487. [PMID: 32129507 DOI: 10.1002/jmv.25745] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Accepted: 03/01/2020] [Indexed: 02/05/2023]
Abstract
This study aims to evaluate the clinical effectiveness in terms of sustained virological response (SVR), predictors of SVR and safety of available second-generation generic direct-acting antivirals in Pakistani chronic hepatitis C patients. This is a retrospective study conducted in multiple centers of Pakistan from January 2015 to January 2019. The samples include patients infected with chronic hepatitis C virus, regardless of virus genotype, cirrhosis, or prior treatment. A total of 993 patients were included in the present study, with the majority receiving sofosbuvir with daclatasvir (95%), sofosbuvir with daclatasvir and ribavirin (4%), and sofosbuvir with ribavirin (1%). There were 96% cases of chronic hepatitis, 3% cases compensated cirrhosis, and 1% cases of decompensated cirrhosis. Genotype 3 (99.6%) was the most common genotype. Overall SVR after 12 weeks was 98% for all treatment regimens. High SVR12 was observed with sofosbuvir in combination with daclatasvir (98.5%), then sofosbuvir in combination with daclatasvir and ribavirin (90.2%) and sofosbuvir in combination with ribavirin (75%). SVR rates were high in chronic hepatitis C patients (98.2%) as compared with cirrhotic patients (92.1%) and it was high in treatment-naive (98.8%) then interferon experienced patients (90.1%). In multivariate binary logistic regression analysis, patients' education status, treatment strategy, viral load, and alanine aminotransferase had a statistically significant association with SVR at 12 weeks. No major adverse events occurred which required treatment discontinuation. Generic oral direct acting antiviralss (sofosbuvir with daclatasvir) achieved higher SVR12 rates and were well tolerated in this large real-world cohort of genotype 3 infected patients.
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Affiliation(s)
- Saima Mushtaq
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan
| | - Atika Mansoor
- Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan
| | - Muhammad Umar
- Centre for Liver and Digestive Diseases, Holy Family Hospital, Rawalpindi Medical College and Allied Hospitals, Rawalpindi, Pakistan
| | - Amjad Khan
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan
| | - Saima Siddiqi
- Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan
| | - Sobia Manzoor
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan
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Sarrazin C, Zimmermann T, Berg T, Hinrichsen H, Mauss S, Wedemeyer H, Zeuzem S. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2020; 58:1110-1131. [PMID: 33197953 DOI: 10.1055/a-1226-0241] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- C Sarrazin
- Medizinische Klinik II Gastroenterologie, Hepatologie, Infektiologie, Diabetologie, St. Josefs-Hospital, Wiesbaden, Deutschland
- Medizinische Klinik I Gastroenterologie, Hepatologie, Pneumologie, Endokrinologie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - T Zimmermann
- Medizinische Klinik II, Klinikum Worms, Worms, Deutschland
- Medizinische Klinik und Poliklinik, Gastroenterologie und Hepatologie, Universitätsmedizin Mainz, Mainz, Deutschland
| | - T Berg
- Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | | | - S Mauss
- MVZ, Düsseldorf, Deutschland
| | - H Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover, Deutschland
| | - S Zeuzem
- Medizinische Klinik I Gastroenterologie, Hepatologie, Pneumologie, Endokrinologie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
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Chiu HC, Chiu YC, Yang EH, Chang TT, Chien SC, Wu IC, Wu CH, Cheng PN. Effectiveness and safety of ledipasvir/sofosbuvir for genotype 2 chronic hepatitis C infection: Real-world experience from Taiwan. J Formos Med Assoc 2020; 120:983-990. [PMID: 32891488 DOI: 10.1016/j.jfma.2020.08.033] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2019] [Revised: 05/27/2020] [Accepted: 08/20/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND/PURPOSE Genotype 2 (GT2) hepatitis C virus infection is the second common genotype in Taiwan. Real-world experience of ledipasvir/sofosbuvir (LDV/SOF) for GT2 infection is limited. The aim of this study is to evaluate the effectiveness and safety of LDV/SOF in patients with GT2 chronic hepatitis C (CHC) infection. METHODS CHC patients with GT2 infection receiving 12 weeks LDV/SOF from three hospitals were enrolled. HCV RNA was checked at baseline, end-of-treatment and 12 weeks after completing treatment. Demographic data, adverse events, renal function and metabolic profiles were recorded. RESULTS Among 392 enrolled patients, 33 patients (8.4%) were cirrhotic. Sustained virological response (SVR) rate was 96.7% (379/392) by intention-to-treat analysis and 97.2% (379/390) by per-protocol analysis. The SVR rate was lower in cirrhotic patients than in non-cirrhotic patients (90.6% vs 97.8%, p = 0.053). Two cirrhotic patients who took LDV/SOF plus ribavirin both achieved SVR. Neither drug-related severe adverse events nor discontinuation due to drug-related adverse event were reported. The estimated glomerular filtration rate (eGFR) remained stable in patients with chronic kidney disease 3a/3b. CONCLUSION Twelve weeks of LDV/SOF treatment provided an excellent and safe regimen for GT2 CHC infection, particularly in non-cirrhotic patients.
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Affiliation(s)
- Hung-Chih Chiu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yen-Cheng Chiu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Er-Hsiang Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ting-Tsung Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Shih-Chieh Chien
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - I-Chin Wu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chun-Hsien Wu
- Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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Mushtaq S, Akhter TS, Khan A, Sohail A, Khan A, Manzoor S. Efficacy and Safety of Generic Sofosbuvir Plus Daclatasvir and Sofosbuvir/Velpatasvir in HCV Genotype 3-Infected Patients: Real-World Outcomes From Pakistan. Front Pharmacol 2020; 11:550205. [PMID: 32982753 PMCID: PMC7493013 DOI: 10.3389/fphar.2020.550205] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 08/17/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Direct-acting antivirals (DAAs) therapeutic regimens are highly effective against chronic hepatitis C virus (HCV) infection. However, HCV patients with genotype 3 (GT3) respond in a suboptimal way. This study aims to identify which of the DAAs-based therapeutic regimens are the best option for GT3. METHODS Multiple governments and private tertiary care hospitals were involved in this real-life study of HCV-GT3 patients treated with DAAs. The efficacy and safety of generic sofosbuvir+daclatasvir±ribavirin (SOF+DCV±RBV) and sofosbuvir/velpatasvir±ribavirin (SOF/VEL±RBV) were assessed under the National Hepatitis C Program of Pakistan. RESULTS Out of 1,388 participants, 70% of patients received SOF+DCV in government tertiary care hospitals and 30% received SOF/VEL in private tertiary care hospitals. The overall sustained virological responses (SVR) was 95.5%. The SVR rates at 12 weeks were comparable between SOF+DCV (94.4%) and SOF/VEL (94.7%) in chronic HCV patients. However, The SVR rates at 24 weeks were high in cirrhotic patients treated with SOF/VEL+RBV (88%) then SOF+DCV+RBV (83%). Non-responders were high in SOF-DCV than SOF-VEL (4.1 vs 3.8%, P = 0.05) regimen. In multivariate models, the significant predictors of non-SVR were age >60 years (odds ratio [OR] 4.46; 95% CI, 2.35-8.46, P = <0.001) and cirrhosis (OR 53.91; 95% CI, 26.49-109.6, P = <0.001). Skin rash (51 vs 44%) and oral ulcers (45 vs 40%) were high in patients receiving SOF-DCV then SOF-VEL. CONCLUSIONS Overall, the generic SOF+DCV ±RBV and SOF/VEL ± RBV achieved equally high SVR12 rates. However, SOF/VEL+RBV achieved a high SVR rate in cirrhotic patients then SOF+DCV+RBV. Old age and cirrhosis were significant predictors of reduced odds of SVR regardless of the regimen. Furthermore, the regimens were well tolerated in chronic HCV patients.
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Affiliation(s)
- Saima Mushtaq
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan
| | - Tayyab Saeed Akhter
- Centre for Liver and Digestive Diseases, Holy Family Hospital, Rawalpindi Medical College and Allied Hospitals, Rawalpindi, Pakistan
| | - Amjad Khan
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan
| | - Aamir Sohail
- Department of Medicine, Karachi Institute of Medical Sciences, Combined Military Hospital, Karachi, Pakistan
| | - Arshad Khan
- Department of Neurosurgery, Medical Teaching Institution, Lady Reading Hospital, Peshawar, Pakistan
| | - Sobia Manzoor
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan
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Mangia A, Milligan S, Khalili M, Fagiuoli S, Shafran SD, Carrat F, Ouzan D, Papatheodoridis G, Ramji A, Borgia SM, Wedemeyer H, Losappio R, Pérez‐Hernandez F, Wick N, Brown RS, Lampertico P, Doucette K, Ntalla I, Ramroth H, Mertens M, Vanstraelen K, Turnes J. Global real-world evidence of sofosbuvir/velpatasvir as simple, effective HCV treatment: Analysis of 5552 patients from 12 cohorts. Liver Int 2020; 40:1841-1852. [PMID: 32449966 PMCID: PMC7496473 DOI: 10.1111/liv.14537] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Revised: 04/24/2020] [Accepted: 05/17/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND AIMS Achieving sustained virological response (SVR; cure) in hepatitis C patients using a simple regimen is key to making elimination by 2030 possible. In the largest real-world analysis to date, the effectiveness of pangenotypic, panfibrotic, single-tablet, sofosbuvir/velpatasvir (SOF/VEL) once-daily for 12 weeks was assessed in 12 clinical real-world cohorts from various geographical areas, settings and treatment practices. Factors affecting risk of not achieving SVR were assessed. METHODS Adults treated with SOF/VEL 400/100 mg, without ribavirin, were included. All HCV patients reaching Week 12 or 24 post-treatment were assessed for SVR12/24. Factors associated with not achieving SVR12/24 for virological reasons were evaluated using logistic regression analysis. RESULTS Overall, 5552 patients were included: 13.3% treatment-experienced; 20.7% compensated cirrhotic; 30.2% genotype 1; 29.5% genotype 2; 32.9% genotype 3; 4.7% genotype 4; 3.7% HIV coinfection; 13.4% current/former intravenous drug use. Of the 5196 patients evaluated for effectiveness, 98.9% achieved SVR12/24. High SVR12/24 rates occurred in all genotypes including genotype 3 (98.3%; 1649/1677) and in those with compensated cirrhosis (97.9; 1055/1078). Only 55 patients did not achieve SVR12/24 due to a virological reason; the only factor statistically significantly associated with an increased risk of not achieving SVR12/24 was compensated cirrhosis (P = .002). Overall, 6% (332/5552) of patients did not achieve SVR12/24 for non-virological reasons (67% lost to follow-up; 26.5% early treatment discontinuation). CONCLUSIONS In this large cohort, representative of clinical practice, a simple 12-week regimen of SOF/VEL without ribavirin resulted in high SVR12/24 rates in diverse patient populations, even among those with compensated cirrhosis.
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Affiliation(s)
| | | | | | | | | | - Fabrice Carrat
- Sorbonne UniversitéINSERMInstitut Pierre Louis Epidémiologie et Santé PubliqueAPHP.Sorbonne UniversitéParisFrance
| | - Denis Ouzan
- Institut Arnault TzanckSaint‐Laurent‐du‐VarFrance
| | | | | | | | | | | | | | | | - Robert S. Brown
- Weill Cornell MedicineDepartment of MedicineNew York CityUSA
| | - Pietro Lampertico
- Fondazione IRCCS Ca’ GrandaOspedale Maggiore PoliclinicoUniversity of MilanMilanItaly
| | | | - Ioanna Ntalla
- Gilead Sciences Europe LtdStockley ParkUnited Kingdom
| | | | | | | | - Juan Turnes
- Department of Gastroenterology and HepatologyC.H.U. Pontevedra and IIS Galicia SurPontevedraSpain
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Brain D, Mitchell J, O’Beirne J. Cost-effectiveness analysis of an outreach model of Hepatitis C Virus (HCV) assessment to facilitate HCV treatment in primary care. PLoS One 2020; 15:e0234577. [PMID: 32555696 PMCID: PMC7299404 DOI: 10.1371/journal.pone.0234577] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Accepted: 05/27/2020] [Indexed: 12/27/2022] Open
Abstract
The effects of hepatitis C virus (HCV), such as morbidity and mortality associated with cirrhosis and liver cancer, is a major public health issue in Australia. Highly effective treatment has recently been made available to all Australians living with HCV. A decision-analytic model was developed to evaluate the cost-effectiveness of the hepatology partnership, compared to usual care. A Markov model was chosen, as it is state-based and able to include recursive events, which accurately reflects the natural history of the chronic and repetitive nature of HCV. Cost-effectiveness of the new model of care is indicated by the incremental cost-effectiveness ratio (ICER), where the mean change to costs associated with the new model of care is divided by the mean change in quality adjusted life-years (QALYs). Ten thousand iterations of the model were run, with the majority (73%) of ICERs representing cost-savings. In comparison to usual care, the intervention improves health outcomes (22.38 QALYs gained) and reduces costs by $42,122 per patient. When compared to usual care, a partnership approach to management of HCV is cost-effective and good value for money, even when key model parameters are changed in scenario analyses. Reduction in costs is driven by improved efficiency of the new model of care, where more patients are treated in a timely manner, away from the expensive tertiary setting. From an economic perspective, a reduction in hospital-based care is a positive outcome and represents a good investment for decision-makers who wish to maximise health gain per dollar spent.
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Affiliation(s)
- David Brain
- Australian Centre for Health Services Innovation, Melbourne, Australia
- School of Public Health and Social Work, Queensland University of Technology, Brisbane, Australia
- * E-mail:
| | - Jonathan Mitchell
- Sunshine Coast University Hospital, Britinya, Australia
- Sunshine Coast Health Institute, University of the Sunshine Coast, Britinya, Australia
| | - James O’Beirne
- Sunshine Coast University Hospital, Britinya, Australia
- Sunshine Coast Health Institute, University of the Sunshine Coast, Britinya, Australia
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Tran AN, Lim JK. Hepatitis C: How Good Are Real-Life Data and Do Generics Work. Gastroenterol Clin North Am 2020; 49:279-299. [PMID: 32389363 DOI: 10.1016/j.gtc.2020.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Chronic hepatitis C virus infection remains a national and global public health burden and is associated with significant morbidity and mortality. Oral direct-acting antiviral combination regimens have excellent tolerability and efficacy with rates exceeding 90%. Sustained virologic response is associated with significant improvements in clinical outcomes. However, translation of sustained virologic response rates from trials to community settings has been poor with interferon-based regimens. We review and summarize key datasets from major real-world observational cohort studies. We review preliminary data from oral generic direct-acting antiviral formulations. Future real-world studies are needed to further clarify optimal treatment strategies for difficult-to-treat populations.
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Affiliation(s)
- Ashley N Tran
- Section of Digestive Diseases, Yale Liver Center, Yale University School of Medicine, New Haven, CT, USA
| | - Joseph K Lim
- Section of Digestive Diseases, Yale Liver Center, Yale University School of Medicine, New Haven, CT, USA; Yale Viral Hepatitis Program, Yale University School of Medicine, 333 Cedar Street, LMP 1080, New Haven, CT 06520-8019, USA.
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Yu ML, Chen PJ, Dai CY, Hu TH, Huang CF, Huang YH, Hung CH, Lin CY, Liu CH, Liu CJ, Peng CY, Lin HC, Kao JH, Chuang WL. 2020 Taiwan consensus statement on the management of hepatitis C: part (I) general population. J Formos Med Assoc 2020; 119:1019-1040. [PMID: 32359879 DOI: 10.1016/j.jfma.2020.04.003] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 03/19/2020] [Accepted: 04/05/2020] [Indexed: 12/16/2022] Open
Abstract
Hepatitis C virus (HCV) infection remains a major public health issue with high prevalence in Taiwan. Recently, the advent of direct-acting antiviral (DAA) agents, with higher efficacy, excellent safety profile, and truncated treatment duration, has revolutionized the paradigm of hepatitis C treatment and made HCV elimination possible. To provide timely guidance for optimal hepatitis C management, the Taiwan Association for the Study of the Liver (TASL) established an expert panel to publish a 2-part consensus statement on the management of hepatitis C in the DAA era. After comprehensive literature review and a consensus meeting, patient-oriented, genotype-guided recommendations on hepatitis C treatment for the general and special populations have been provided based on the latest indications and scientific evidence. In the first part of this consensus, we present the epidemiology and treatment situation of hepatitis C in Taiwan, the development of DAA, pre-treatment evaluation, post sustained virologic response (SVR) monitoring, and most importantly the treatment recommendations for the general population with compensated liver disease. The second part will focus on the treatment recommendations for the special populations.
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Affiliation(s)
- Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Pei-Jer Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
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Soria A, Fava M, Bernasconi DP, Lapadula G, Colella E, Valsecchi MG, Migliorino GM, D'Ambrosio R, Landonio S, Schiavini M, Spinetti A, Carriero C, Degasperi E, Cologni G, Gatti F, Viganò P, Hasson H, Uberti-Foppa C, Pasulo L, Baiguera C, Rossotti R, Vinci M, Puoti M, Giorgini A, Menzaghi B, Lombardi A, Pan A, Aghemo A, Grossi PA, Boldizzoni R, Colombo S, Viganò M, Rumi MG, Del Poggio P, Valenti L, Giglio O, De Bona A, d'Arminio Monforte A, Colombo A, Spinelli O, Pigozzi MG, Molteni C, Bonfanti P, Terreni N, Perini P, Capretti A, Bella D, Liani C, Polo S, Aimo G, Pagnucco L, Bhoori S, Centenaro R, Graffeo M, Ciaccio A, Dionigi E, Lazzaroni S, Carderi I, Di Marco M, Rizzardini G, Noventa F, Lampertico P, Fagiuoli S. Comparison of three therapeutic regimens for genotype-3 hepatitis C virus infection in a large real-life multicentre cohort. Liver Int 2020; 40:769-777. [PMID: 31970845 DOI: 10.1111/liv.14386] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Revised: 01/10/2020] [Accepted: 01/15/2020] [Indexed: 01/24/2023]
Abstract
BACKGROUND & AIMS In the direct-acting antiviral era, treatment of genotype-3 HCV (HCV-GT3) is still challenging. Real-life comparisons between recommended regimens, sofosbuvir (SOF)+daclatasvir (DAC), SOF/velpatasvir (VEL), glecaprevir/pibrentasvir (GLE/PIB), are scarce. We aimed at filling this data gap. METHODS Sustained virological response 12 weeks after treatment completion (SVR12) was assessed for all HCV-GT3 patients consecutively treated within the Lombardia web-based Navigatore HCV-Network; differences in SVR12 across regimens were evaluated by logistic regression. RESULTS Of the 2082 subjects with HCV-GT3, 1544 were evaluable for comparisons between regimens: SOF + DAC (1023, 66.2%), SOF/VEL (369, 23.9%), GLE/PIB (152, 9.8%). Patients treated with former regimens were more frequently male, cirrhotic, HIV-positive, pretreated, used ribavirin in their regimen, and had lower baseline HCV-RNA. SVR12 was similar across groups: 94.8% in SOF + DAC, 97.6% in SOF/VEL, 96.7% in GLE/PIB (P = .065). At univariate analysis, SVR12 was associated with female gender (97.9% vs 94.8%, P = .007) and lower median pretreatment Log10 HCV-RNA (5.87 vs 6.20, P = .001). At multivariate logistic regression analysis, treatment with SOF/VEL was associated with a higher likelihood of SVR12 than SOF + DAC, but only in the absence of ribavirin (98% vs 90.3%). Female gender and lower pretreatment HCV-RNA were independently associated with SVR12. CONCLUSIONS In a large real-life setting of HCV-GT3-infected patients with a high proportion of cirrhosis, the success rate was remarkable. The slight advantage of SOF/VEL on SOF + DAC was significant only without ribavirin. The current prescription shift towards novel regimens (ie SOF/VEL and GLE/PIB) in easier-to-treat patients allows ribavirin-free and shorter schedules without mining SVR12 in this <<difficult-to-treat>> genotype.
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Affiliation(s)
- Alessandro Soria
- Division of Infectious Diseases, San Gerardo Hospital - ASST Monza, Monza, Italy
| | - Marco Fava
- Division of Infectious Diseases, San Gerardo Hospital - ASST Monza, Monza, Italy.,Medical School, University of Milano-Bicocca, Milan, Italy
| | - Davide P Bernasconi
- Center of Biostatistics for Clinical Epidemiology, School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Giuseppe Lapadula
- Division of Infectious Diseases, San Gerardo Hospital - ASST Monza, Monza, Italy
| | - Elisa Colella
- Division of Infectious Diseases, San Gerardo Hospital - ASST Monza, Monza, Italy
| | - Maria G Valsecchi
- Center of Biostatistics for Clinical Epidemiology, School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | | | - Roberta D'Ambrosio
- Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milano, Italy
| | - Simona Landonio
- Infectious Diseases, Ospedale Luigi Sacco - ASST Fatebenefratelli Sacco, Milano, Italy
| | - Monica Schiavini
- Infectious Diseases, Ospedale Luigi Sacco - ASST Fatebenefratelli Sacco, Milano, Italy
| | - Angiola Spinetti
- Infectious Diseases, Spedali Civili - ASST Brescia, Brescia, Italy
| | - Canio Carriero
- Infectious Diseases, Spedali Civili - ASST Brescia, Brescia, Italy
| | - Elisabetta Degasperi
- Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milano, Italy
| | | | | | - Paolo Viganò
- Ospedale di Legnano - ASST Ovest Milano, Legnano, Italy
| | - Hamid Hasson
- Infectious Diseases, San Raffaele Scientific Institute IRCCS, Milano, Italy
| | | | - Luisa Pasulo
- ASST Papa Giovanni XXIII, Bergamo HCV Network, Bergamo, Italy
| | - Chiara Baiguera
- Hepatitis Center, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
| | - Roberto Rossotti
- Hepatitis Center, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
| | - Maria Vinci
- Hepatitis Center, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
| | - Massimo Puoti
- Hepatitis Center, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
| | | | - Barbara Menzaghi
- Division of Infectious Diseases, Ospedale di Busto Arsizio - ASST Valle Olona, Busto Arsizio, Italy
| | - Andrea Lombardi
- Infectious Diseases, Fondazione IRCCS Policlinico San Matteo di Pavia, Pavia, Italy
| | - Angelo Pan
- Division of Infectious Diseases, ASST Cremona, Cremona, Italy
| | - Alessio Aghemo
- Internal Medicine and Hepatology, Humanitas Research Hospital IRCCS and Humanitas University, Rozzano, Italy
| | - Paolo A Grossi
- Ospedale di Circolo e Fondazione Macchi Varese - ASST Sette Laghi, Infectious Diseases, Università dell'Insubria, Varese, Italy
| | | | | | - Mauro Viganò
- Ospedale San Giuseppe, University of Milan, Milano, Italy
| | - Maria G Rumi
- Ospedale San Giuseppe, University of Milan, Milano, Italy
| | | | - Luca Valenti
- Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milano, Italy
| | | | - Anna De Bona
- Ospedale San Paolo - ASST Santi Paolo e Carlo, Milano, Italy
| | | | | | | | - Marie G Pigozzi
- Infectious Diseases, Spedali Civili - ASST Brescia, Brescia, Italy
| | - Chiara Molteni
- Division of Infectious Diseases, ASST Lecco, Lecco, Italy
| | - Paolo Bonfanti
- Division of Infectious Diseases, ASST Lecco, Lecco, Italy
| | | | - Paolo Perini
- Policlinico San Pietro, Bergamo HCV Network, Ponte San Pietro, Italy
| | - Andrea Capretti
- San Carlo Hospital - ASST Santi Paolo e Carlo, Milano, Italy
| | | | | | | | | | - Layla Pagnucco
- Infectious Diseases, Fondazione IRCCS Policlinico San Matteo di Pavia, Pavia, Italy
| | - Sherrie Bhoori
- Gastro-Hepato-Pancreatic Surgery and Liver Transplant Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy
| | - Riccardo Centenaro
- Ospedale di Vizzolo Predabissi - ASST Melegnano e Martesana, Vizzolo Predabissi, Italy
| | - Massimo Graffeo
- UO Gastroenterologia ed Endoscopia Digestiva, Epatologia, Fondazione Ospedaliera Poliambulanza, Rete HCV Brescia, Brescia, Italy
| | - Antonio Ciaccio
- Division of Gastroenterology, San Gerardo Hospital - ASST Monza, Monza, Italy
| | - Elena Dionigi
- Ospedale di Cernusco sul Naviglio - ASST Melegnano e Martesana, Cernusco sul Naviglio, Italy
| | | | | | | | - Giuliano Rizzardini
- Infectious Diseases, Ospedale Luigi Sacco - ASST Fatebenefratelli Sacco, Milano, Italy
| | | | - Pietro Lampertico
- Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milano, Italy
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Charatcharoenwitthaya P, Wongpaitoon V, Komolmit P, Sukeepaisarnjaroen W, Tangkijvanich P, Piratvisuth T, Sanpajit T, Sutthivana C, Bunchorntavakul C, Sobhonslidsuk A, Chonprasertsuk S, Siripipattanamongkol C, Sethasine S, Tanwandee T. Real-world effectiveness and safety of sofosbuvir and nonstructural protein 5A inhibitors for chronic hepatitis C genotype 1, 2, 3, 4, or 6: a multicentre cohort study. BMC Gastroenterol 2020; 20:47. [PMID: 32138687 PMCID: PMC7057522 DOI: 10.1186/s12876-020-01196-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 02/17/2020] [Indexed: 02/07/2023] Open
Abstract
Background We investigated real-world effectiveness and safety of sofosbuvir and the nonstructural protein 5A inhibitors in the treatment of patients infected with hepatitis C virus (HCV) genotypes 1, 2, 3, 4, or 6. Methods We analyzed data from 1021 patients with HCV infection (506 with genotype 1; 16 with genotype 2; 314 with genotype 3; 13 with genotype 4; 166 with genotype 6) who received 12 to 24 weeks of daclatasvir plus sofosbuvir (n = 767), ledipasvir/sofosbuvir (n = 197), or sofosbuvir/velpatasvir (n = 57), with or without ribavirin in 12 centers across Thailand to estimate sustained virologic response at post-treatment week 12 (SVR12). Results Overall, SVR12 rate was 98.0% (95% confidence interval [CI], 96.7–98.8%) with daclatasvir plus sofosbuvir, 97.9% (95% CI, 94.8–99.2%) with ledipasvir/sofosbuvir, and 96.5% (95% CI, 88.1–99.0%) with sofosbuvir/velpatasvir. SVR12 was achieved by 99.2% (95% CI, 97.9–99.7%) of subjects with genotype 1 infection, 100% (95% CI, 78.5–100%) of those with genotype 2 infection, 96.7% (95% CI, 94.0–98.2%) of those with genotype 3 infection, 90.9% (95% CI, 62.3–98.4%) of those with genotype 4 infection, and 96.7% (95% CI 92.5–98.6%) of those with genotype 6 infection. Patients with advanced liver disease were at risk of treatment failure. Only four patients discontinued treatment before week 4 due to non-hepatic adverse events. Conclusions In this large cohort of patients with various HCV genotypes managed in the real-world practice setting, daclatasvir plus sofosbuvir, ledipasvir/sofosbuvir, and sofosbuvir/velpatasvir achieved high SVR rates with good safety profile, comparable to those observed in clinical trials.
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Affiliation(s)
| | | | - Piyawat Komolmit
- Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | | | | | | | | | | | | | | | | | | | | | - Tawesak Tanwandee
- Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Wilton J, Wong S, Yu A, Ramji A, Cook D, Butt ZA, Alvarez M, Binka M, Darvishian M, Jeong D, Bartlett SR, Pearce ME, Adu PA, Yoshida EM, Krajden M, Janjua NZ. Real-world Effectiveness of Sofosbuvir/Velpatasvir for Treatment of Chronic Hepatitis C in British Columbia, Canada: A Population-Based Cohort Study. Open Forum Infect Dis 2020; 7:ofaa055. [PMID: 32154326 PMCID: PMC7052750 DOI: 10.1093/ofid/ofaa055] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 02/12/2020] [Indexed: 12/12/2022] Open
Abstract
Background Clinical trials show high efficacy of sofosbuvir/velpatasvir (SOF/VEL), but there are limited data from “real-world” settings. We aimed to evaluate SOF/VEL effectiveness for all hepatitis C virus (HCV) genotypes (GTs) in British Columbia (BC), Canada. Methods We used the BC Hepatitis Testers Cohort, which includes all HCV cases in the province (1990–2015) linked to administrative databases, including prescriptions to end of 2018. We measured sustained virologic response (SVR; negative RNA ≥10 weeks after treatment end) and identified characteristics associated with non-SVR. Conservatively, we excluded individuals with no assessment for SVR if their last RNA test after treatment initiation was negative (but included if positive). Results Of 2821 eligible participants, most were infected with GT1 (1076, 38.1%) or GT3 (1072, 38.0%), and a minority (278, 9.9%) were treated with RBV. SVR was 94.6% (2670/2821) overall and 94.5% (1017/1076) for GT1, 96.4% (512/531) for GT2, and 93.7% (1004/1072) for GT3. When disaggregated by GT, treatment regimen, and cirrhosis/treatment experience, SVR was lowest (30/40, 75.0%) among treatment-experienced GT3 individuals treated with RBV. Characteristics associated with non-SVR in multivariable analysis included younger age, RBV addition, and being a person with HIV (PWH) or who injects/injected drugs (PWID). When treatment regimen (±RBV) was removed from multivariable model, treatment experience was associated with non-SVR for GT3. Of 151 non-SVR individuals, 56.3% were nonvirological failures (treatment incomplete/no assessment for SVR) and 43.7% were virological failures (nonresponse/relapse). A disproportionately high percentage of non-SVR among PWID was due to nonvirological failure. Conclusions SOF/VEL was highly effective in this “real-world” population-based cohort. Additional support is required for PWID/PWH to reach SVR.
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Affiliation(s)
- James Wilton
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Stanley Wong
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Amanda Yu
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Alnoor Ramji
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Darrel Cook
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Zahid A Butt
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Public Health and Health Systems, University of Waterloo, Waterloo, Ontario, Canada
| | - Maria Alvarez
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Mawuena Binka
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Maryam Darvishian
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,Cancer Control Research, BC Cancer Research Center, Vancouver, British Columbia, Canada.,Population Oncology, BC Cancer Research Center, Vancouver, British Columbia, Canada
| | - Dahn Jeong
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Sofia R Bartlett
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.,Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia
| | - Margo E Pearce
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Prince A Adu
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Eric M Yoshida
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Mel Krajden
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Naveed Z Janjua
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
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48
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Margusino-Framiñán L, Cid-Silva P, Rotea-Salvo S, Mena-de-Cea Á, Suárez-López F, Vázquez-Rodríguez P, Delgado-Blanco M, Sanclaudio-Luhia AI, Martín-Herranz I, Castro-Iglesias Á. Effectiveness and safety of sofosbuvir/velpatasvir ± ribavirin vs glecaprevir/pibrentasvir in genotype 3 hepatitis C virus infected patients. Eur J Hosp Pharm 2020; 27:e41-e47. [PMID: 32296504 DOI: 10.1136/ejhpharm-2019-002060] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Revised: 01/14/2020] [Accepted: 01/16/2020] [Indexed: 12/15/2022] Open
Abstract
Objectives Sofosbuvir/velpatasvir±ribavirin (SOF/VEL±RBV) and glecaprevir/pibrentasvir (GLE/PIB) are the drug combinations of choice for treating individuals with genotype 3 hepatitis C virus (G3-HCV) infection. The objective of this study was to evaluate the effectiveness and safety of SOF/VEL±RBV compared with GLE/PIB for treating G3-HCV infection under routine clinical practice conditions. Methods We conducted a prospective observational cohort study of individuals with G3-HCV infection who initiated treatment with SOF/VEL +/-RBV or GLE/PIB between April 2017 and July 2018. Prisoners and children were excluded. The outcome variable of effectiveness was sustained virological response 12 weeks after completing treatment (SVR12). The safety variable was withdrawal secondary to severe adverse events (SAEs). Covariates included sex, age, HIV co-infection, previous liver transplant, cirrhosis, hepatic fibrosis and previous antiviral treatment. Statistical significance was calculated using Fisher's exact test or the Mann-Whitney U-test. Results A total of 76 patients were included in the analysis, of whom 46 were treated with SOF/VEL±RBV and 30 were treated with GLE/PIB. No baseline differences were observed between treatment groups with respect to age, sex, HIV co-infection, fibrosis stage, cirrhosis and previous antiviral treatment. Of the patients treated with SOF/VEL±RBV and GLE/PIB, 95.7% and 96.7% reached SVR12, respectively (P=0.7). Of patients with and without cirrhosis, 83.3% and 98.4% reached SVR12, respectively (P=0.09). Of the patients with low-grade hepatic fibrosis (F0-2) and advanced fibrosis (F3-4), 100% and 85.7% reached SVR12, respectively (P=0.03). In treatment-naïve and treatment-experienced patients, 95.7% and 100% reached SVR12, respectively (P=0.57), without significant differences independent of the treatment group (P=0.28 for SOF/VEL±RBV; P=0.18 for GLE/PIB). The incidence of AEs was 21.1% (95% CI 11.3% to 30.9%). None of the patients developed an SAE or required antiviral treatment withdrawal. Conclusions SOF/VEL±RBV or GLE/PIB are safe and effective for treating G3-HCV-infections, with a lower effectiveness in patients with advanced fibrosis F3-4.
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Affiliation(s)
- Luis Margusino-Framiñán
- Pharmacy Service, Universitary Hospital of A Coruña, A Coruña, Spain.,Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), Universitary Hospital of A Coruña (CHUAC), Sergas, University of A Coruña (UDC), A Coruña, Spain
| | - Purificación Cid-Silva
- Pharmacy Service, Universitary Hospital of A Coruña, A Coruña, Spain.,Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), Universitary Hospital of A Coruña (CHUAC), Sergas, University of A Coruña (UDC), A Coruña, Spain
| | | | - Álvaro Mena-de-Cea
- Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), Universitary Hospital of A Coruña (CHUAC), Sergas, University of A Coruña (UDC), A Coruña, Spain.,Infectious Diseases Unit. Internal Medicine Service, Universitary Hospital of A Coruña (CHUAC), A Coruña, Spain
| | - Francisco Suárez-López
- Hepatology Unit, Digestive System Service, University Hospital of A Coruña (CHUAC), A Coruña, Spain
| | - Pilar Vázquez-Rodríguez
- Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), Universitary Hospital of A Coruña (CHUAC), Sergas, University of A Coruña (UDC), A Coruña, Spain.,Infectious Diseases Unit. Internal Medicine Service, Universitary Hospital of A Coruña (CHUAC), A Coruña, Spain
| | - Manuel Delgado-Blanco
- Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), Universitary Hospital of A Coruña (CHUAC), Sergas, University of A Coruña (UDC), A Coruña, Spain.,Hepatology Unit, Digestive System Service, University Hospital of A Coruña (CHUAC), A Coruña, Spain
| | | | | | - Ángeles Castro-Iglesias
- Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), Universitary Hospital of A Coruña (CHUAC), Sergas, University of A Coruña (UDC), A Coruña, Spain.,Infectious Diseases Unit. Internal Medicine Service, Universitary Hospital of A Coruña (CHUAC), A Coruña, Spain
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49
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Sustained Virologic Response Rates of Sofosbuvir and Velpatasvir in Patients with Hepatitis C Genotype 3: A Meta-Analysis. HEPATITIS MONTHLY 2020. [DOI: 10.5812/hepatmon.98798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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50
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AASLD-IDSA Hepatitis C Guidance Panel *, Morgan TR, AASLD‐IDSA Hepatitis C Guidance Panel. Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Hepatology 2020; 71:686-721. [PMID: 31816111 PMCID: PMC9710295 DOI: 10.1002/hep.31060] [Citation(s) in RCA: 523] [Impact Index Per Article: 104.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 11/21/2019] [Indexed: 02/06/2023]
Affiliation(s)
| | - Timothy R. Morgan
- Chief of Hepatology Veterans Affairs Long Beach Healthcare System Long Beach CA
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