|
1
|
Zhao L, Hall M, Giridhar P, Ghafari M, Kemp S, Chai H, Klenerman P, Barnes E, Ansari MA, Lythgoe K. Genetically distinct within-host subpopulations of hepatitis C virus persist after Direct-Acting Antiviral treatment failure. PLoS Pathog 2025; 21:e1012959. [PMID: 40168433 PMCID: PMC11981120 DOI: 10.1371/journal.ppat.1012959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 04/09/2025] [Accepted: 02/05/2025] [Indexed: 04/03/2025] Open
Abstract
Analysis of viral genetic data has previously revealed distinct within-host population structures in both untreated and interferon-treated chronic hepatitis C virus (HCV) infections. While multiple subpopulations persisted during the infection, each subpopulation was observed only intermittently. However, it was unknown whether similar patterns were also present after Direct-Acting Antiviral (DAA) treatment, where viral populations were often assumed to go through narrow bottlenecks. Here we tested for the maintenance of population structure after DAA treatment failure, and whether there were different evolutionary rates along distinct lineages where they were observed. We analysed whole-genome next-generation sequencing data generated from a randomised study using DAAs (the BOSON study). We focused on samples collected from patients (N=84) who did not achieve sustained virological response (i.e., treatment failure) and had sequenced virus from multiple timepoints. Given the short-read nature of the data, we used a number of methods to identify distinct within-host lineages including tracking concordance in intra-host nucleotide variant (iSNV) frequencies, applying sequenced-based and tree-based clustering algorithms to sliding windows along the genome, and haplotype reconstruction. Distinct viral subpopulations were maintained among a high proportion of individuals post DAA treatment failure. Using maximum likelihood modelling and model comparison, we found an overdispersion of viral evolutionary rates among individuals, and significant differences in evolutionary rates between lineages within individuals. These results suggest the virus is compartmentalised within individuals, with the varying evolutionary rates due to different viral replication rates and/or different selection pressures. We endorse lineage awareness in future analyses of HCV evolution and infections to avoid conflating patterns from distinct lineages, and to recognise the likely existence of unsampled subpopulations.
Collapse
Affiliation(s)
- Lele Zhao
- Nuffield Department of Medicine, Pandemic Sciences Institute, University of Oxford, Oxford, United Kingdom
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom
| | - Matthew Hall
- Nuffield Department of Medicine, Pandemic Sciences Institute, University of Oxford, Oxford, United Kingdom
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom
| | | | - Mahan Ghafari
- Nuffield Department of Medicine, Pandemic Sciences Institute, University of Oxford, Oxford, United Kingdom
| | - Steven Kemp
- Nuffield Department of Medicine, Pandemic Sciences Institute, University of Oxford, Oxford, United Kingdom
| | - Haiting Chai
- Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom
| | - Paul Klenerman
- Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom
| | - Eleanor Barnes
- Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom
| | - M. Azim Ansari
- Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom
| | - Katrina Lythgoe
- Nuffield Department of Medicine, Pandemic Sciences Institute, University of Oxford, Oxford, United Kingdom
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom
- Department of Biology, University of Oxford, Oxford, United Kingdom
| |
Collapse
|
|
2
|
Swannell M, Bradlow RCJ, Pham D, Gabriel J, Manahan Y, Arunogiri S. Pharmacological treatments for co-occurring PTSD and substance use disorders: A systematic review. JOURNAL OF SUBSTANCE USE AND ADDICTION TREATMENT 2025; 169:209601. [PMID: 39672336 DOI: 10.1016/j.josat.2024.209601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 11/11/2024] [Accepted: 11/29/2024] [Indexed: 12/15/2024]
Abstract
INTRODUCTION Post-traumatic stress disorder and substance use disorders commonly co-occur and are associated with worse health outcomes. Currently, only psychosocial therapies are specifically recommended for use in the co-occurring population, but these come with numerous barriers to access and engagement. This study aims to identify potential pharmacological treatments to enhance treatment options and outcomes for this population. METHODS This systematic review identified studies on pharmacological treatment of co-occurring PTSD and SUD in humans, using validated outcome measurements, with study design of RCT, observational study, case control study or cohort study. RESULTS 29 studies were identified for inclusion, looking at a range of 16 pharmacotherapies. A majority concentrated on alcohol use disorders and males, with many focused on the veteran population. CONCLUSIONS This is an area for further research, inclusive of more SUDs, genders and civilians. Future studies utilizing consistent dosing, populations and measurement outcomes will allow for future meta-analysis.
Collapse
Affiliation(s)
- Megan Swannell
- Eastern Health Mental Health Service, Victoria, Australia
| | | | - Daniel Pham
- Turning Point, Eastern Health, Victoria, Australia
| | | | - Yasmin Manahan
- Eastern Health Mental Health Service, Victoria, Australia
| | - Shalini Arunogiri
- Turning Point, Eastern Health, Victoria, Australia; Eastern Health Clinical School and Monash Addiction Research Centre, Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Australia.
| |
Collapse
|
|
3
|
Di Marco L, Cannova S, Ferrigno E, Landro G, Nonni R, Mantia CL, Cartabellotta F, Calvaruso V, Di Marco V. A Comprehensive Review of Antiviral Therapy for Hepatitis C: The Long Journey from Interferon to Pan-Genotypic Direct-Acting Antivirals (DAAs). Viruses 2025; 17:163. [PMID: 40006918 PMCID: PMC11860415 DOI: 10.3390/v17020163] [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] [Received: 12/30/2024] [Revised: 01/19/2025] [Accepted: 01/20/2025] [Indexed: 02/27/2025] Open
Abstract
The treatment landscape for hepatitis C virus (HCV) infection has transformed over the past few decades, evolving from the limited efficacy of interferon (IFN) monotherapy to the highly successful pan-genotypic direct-acting antivirals (DAAs) used today. Initially, alpha-interferon monotherapy, introduced in the 1990s, was the standard treatment, yet it provided low sustained virological response (SVR) rates and caused significant adverse effects, limiting its utility. The development of pegylated interferon (peg-IFN) improved the pharmacokinetic profile of IFN, allowing for less frequent dosing and modestly improved response rates. When combined with ribavirin, peg-IFN achieved higher SVR rates, especially in non-genotype 1 HCV infections, but the combination also brought additional side effects, such as anemia and depression. The advent of the first-generation DAAs, such as telaprevir and boceprevir, marked a significant milestone. Combined with peg-IFN and ribavirin, these protease inhibitors boosted response rates in patients with genotype 1 HCV. However, high rates of adverse effects and drug resistance remained challenges. Second-generation DAAs, like sofosbuvir and ledipasvir, introduced IFN-free regimens with improved safety profiles and efficacy. The most recent advances are pan-genotypic DAAs, including glecaprevir-pibrentasvir and sofosbuvir-velpatasvir, which offer high SVR rates across all genotypes, shorter treatment durations, and fewer side effects. Current pan-genotypic regimens represent a cornerstone in HCV therapy, providing an accessible and effective solution globally.
Collapse
Affiliation(s)
- Lorenza Di Marco
- SIcilian Network for Therapy, Epidemiology and Screening In Hepatology (SINTESI), 90127 Palermo, Italy; (L.D.M.); (F.C.); (V.C.)
- Department of Oncology and Hematology, Azienda Ospedaliero-University Hospital of Mod, 41124 Modena, Italy
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41100 Modena, Italy
| | - Simona Cannova
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy; (S.C.); (E.F.); (G.L.); (R.N.); (C.L.M.)
| | - Emanuele Ferrigno
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy; (S.C.); (E.F.); (G.L.); (R.N.); (C.L.M.)
| | - Giuseppe Landro
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy; (S.C.); (E.F.); (G.L.); (R.N.); (C.L.M.)
| | - Rosario Nonni
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy; (S.C.); (E.F.); (G.L.); (R.N.); (C.L.M.)
| | - Claudia La Mantia
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy; (S.C.); (E.F.); (G.L.); (R.N.); (C.L.M.)
| | - Fabio Cartabellotta
- SIcilian Network for Therapy, Epidemiology and Screening In Hepatology (SINTESI), 90127 Palermo, Italy; (L.D.M.); (F.C.); (V.C.)
- Department of Medicine, Buccheri-La Ferla Hospital, 90123 Palermo, Italy
| | - Vincenza Calvaruso
- SIcilian Network for Therapy, Epidemiology and Screening In Hepatology (SINTESI), 90127 Palermo, Italy; (L.D.M.); (F.C.); (V.C.)
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy; (S.C.); (E.F.); (G.L.); (R.N.); (C.L.M.)
| | - Vito Di Marco
- SIcilian Network for Therapy, Epidemiology and Screening In Hepatology (SINTESI), 90127 Palermo, Italy; (L.D.M.); (F.C.); (V.C.)
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy; (S.C.); (E.F.); (G.L.); (R.N.); (C.L.M.)
| |
Collapse
|
|
4
|
Hiew TN, Solomos MA, Kafle P, Polyzois H, Zemlyanov DY, Punia A, Smith D, Schenck L, Taylor LS. The importance of surface composition and wettability on the dissolution performance of high drug loading amorphous dispersion formulations. J Pharm Sci 2025; 114:289-303. [PMID: 39349295 DOI: 10.1016/j.xphs.2024.09.020] [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] [Received: 06/27/2024] [Revised: 09/19/2024] [Accepted: 09/19/2024] [Indexed: 10/02/2024]
Abstract
One of the limitations with an amorphous solid dispersion (ASD) formulation strategy is low drug loading. Hydrophobic drugs have poor wettability and require a substantial amount of polymer to stabilize the amorphous drug and facilitate release. Using grazoprevir and hypromellose acetate succinate as model drug and polymer, respectively, the interplay between particle surface composition, particle wettability, and release performance was investigated. A hierarchical particle approach was used where the surfaces of high drug loading ASDs generated by either solvent evaporation or co-precipitation were further modified with a secondary excipient (i.e., polymer or wetting agent). The surface-modified particles were characterized for drug release, wettability, morphology, and surface composition using two-stage dissolution studies, contact angle measurements, scanning electron microscopy, and X-ray photoelectron spectroscopy, respectively. Despite surface modification with hydrophilic polymers, the hierarchical particles did not consistently exhibit good release performance. Contact angle measurements showed that the secondary excipient had a profound impact on particle wettability. Particles with good wettability showed improved drug release relative to particles that did not wet well, even with similar drug loadings. These observations underscore the intricate interplay between particle wettability and performance in amorphous dispersion formulations and illustrate a promising hierarchical particle approach to formulate high drug loading amorphous dispersions with improved dissolution performance.
Collapse
Affiliation(s)
- Tze Ning Hiew
- Department of Industrial and Molecular Pharmaceutics, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907, United States
| | - Marina A Solomos
- Oral Formulation Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States
| | - Prapti Kafle
- Oral Formulation Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States
| | - Hector Polyzois
- Department of Industrial and Molecular Pharmaceutics, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907, United States
| | - Dmitry Y Zemlyanov
- Birck Nanotechnology Center, Purdue University, West Lafayette, Indiana 47907, United States
| | - Ashish Punia
- Analytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States
| | - Daniel Smith
- Analytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States
| | - Luke Schenck
- Oral Formulation Sciences, Merck & Co., Inc., Rahway, New Jersey 07065, United States
| | - Lynne S Taylor
- Department of Industrial and Molecular Pharmaceutics, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907, United States.
| |
Collapse
|
|
5
|
O'Brien TR, Witt DJ, Saxena V, Morrissey KG, Chen S, Baker FS, Prokunina-Olsson L, Pfeiffer RM, Lai JB. IFNL4 genotype and other personal characteristics to predict response to 8-week sofosbuvir-based treatment for chronic hepatitis C. J Infect 2024; 89:106258. [PMID: 39216831 PMCID: PMC11490369 DOI: 10.1016/j.jinf.2024.106258] [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: 05/17/2024] [Revised: 08/15/2024] [Accepted: 08/23/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Shorter duration therapy for hepatitis C virus (HCV) infection might reduce treatment costs and increase the number of patients treated and cured. We determined factors associated with treatment response after an 8-week sofosbuvir-based therapy and developed a simple model to predict an individual's likelihood of treatment success. METHODS Among 2907 patients who received ledipasvir/sofosbuvir for 8 weeks, we determined failure rates by demographic and clinical characteristics, and IFNL4-∆G/TT genotype. We estimated the average IFNL4 genotype-related treatment failure rate in major ancestry groups by applying our IFNL4 genotype results to genotype distributions from reference populations. We created a treatment response model based on three personal characteristics. RESULTS Overall, 4.4% of the patients failed treatment. We observed significantly lower failure rates for persons <50 years (1.6%), females (2.6%), those carrying the IFNL4-TT/TT genotype (1.8%), those with HCV RNA <5.8 log10 copies/mL (2.0%) or HCV genotype-1B infection (2.6%). In a model based on ancestry, age and sex, the predicted probability of treatment failure ranged from 0.5% among females of East Asian ancestry <50 years of age to 8.5% among males of African ancestry age ≥65 years. CONCLUSION Applying this algorithm at the point-of-care might facilitate HCV elimination, especially in low- and middle-income countries.
Collapse
Affiliation(s)
- Thomas R O'Brien
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, United States.
| | - David J Witt
- Kaiser Permanente San Rafael Medical Center, San Rafael, CA, United States.
| | - Varun Saxena
- Kaiser Permanente South San Francisco Medical Center, South San Francisco, CA, United States; University of California San Francisco, San Francisco, CA, United States.
| | | | - Sabrina Chen
- Information Management Services, Inc, Calverton, MD, United States.
| | - Francine S Baker
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, United States; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, United States.
| | - Ludmila Prokunina-Olsson
- Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, United States.
| | - Ruth M Pfeiffer
- Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, United States.
| | - Jennifer B Lai
- Kaiser Permanente San Rafael Medical Center, San Rafael, CA, United States.
| |
Collapse
|
|
6
|
Smirne C, Crobu MG, Gerevini C, Berton AM, Rapetti R, Pasini B, Ravanini P, Pirisi M. The Impact of the G6PD Gene Mutations in Patients with Chronic Hepatitis C Infection Treated with Direct-Acting Antivirals: A Multicenter Observational Study. Genes (Basel) 2024; 15:1116. [PMID: 39336707 PMCID: PMC11431558 DOI: 10.3390/genes15091116] [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] [Received: 07/22/2024] [Revised: 08/20/2024] [Accepted: 08/22/2024] [Indexed: 09/30/2024] Open
Abstract
Following the advent of direct-acting antivirals (DAAs), the treatment of hepatitis C virus (HCV) infection is now rarely challenging. However, data are still limited concerning DAA use in patients affected by glucose-6-phosphate dehydrogenase deficiency (G6PDd). Based on these considerations, the goal of this study was to evaluate the effectiveness and safety of DAAs in this subpopulation. A retrospective multicenter observational study (2015-2023) was conducted on all 2754 consecutive HCV-positive patients treated with first- and second-generation all-oral DAAs, and with a G6PDd diagnosis confirmed by quantitative testing (n = 38). At the treating clinician's discretion, an enhanced clinical and laboratory follow-up was performed, generally on a monthly basis both during treatment and up to six months after the end of it. Concerning hematochemical parameters, no significant differences were found between any considered time point. In all cases, no treatment-related adverse events were reported, and virologic response rates were as expected without G6PDd. In conclusion, in a large experience which, to the best of our knowledge, is unprecedented in the literature, the treatment of HCV hepatitis with nearly all available DAAs in patients with G6PDd as a comorbidity-a common occurrence in countries such as Italy-proved to be highly effective and safe.
Collapse
Affiliation(s)
- Carlo Smirne
- Internal Medicine Unit, Maggiore della Carità Hospital, 28100 Novara, Italy; (C.G.); (R.R.); (M.P.)
- Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy
| | - Maria Grazia Crobu
- Laboratory of Molecular Virology, Maggiore della Carità Hospital, 28100 Novara, Italy; (M.G.C.); (P.R.)
- Clinical Biochemistry Laboratory, City of Health and Science University Hospital, 10126 Turin, Italy
| | - Chiara Gerevini
- Internal Medicine Unit, Maggiore della Carità Hospital, 28100 Novara, Italy; (C.G.); (R.R.); (M.P.)
| | - Alessandro Maria Berton
- Division of Endocrinology, Diabetes and Metabolism, City of Health and Science University Hospital, 10126 Turin, Italy;
| | - Rachele Rapetti
- Internal Medicine Unit, Maggiore della Carità Hospital, 28100 Novara, Italy; (C.G.); (R.R.); (M.P.)
| | - Barbara Pasini
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy;
- Division of Medical Genetics, City of Health and Science University Hospital, 10126 Turin, Italy
| | - Paolo Ravanini
- Laboratory of Molecular Virology, Maggiore della Carità Hospital, 28100 Novara, Italy; (M.G.C.); (P.R.)
| | - Mario Pirisi
- Internal Medicine Unit, Maggiore della Carità Hospital, 28100 Novara, Italy; (C.G.); (R.R.); (M.P.)
- Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy
| |
Collapse
|
|
7
|
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.
Collapse
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
| |
Collapse
|
|
8
|
Alshoaibi IA, Al-Gamli A, Abdullah M, Abdo B, Alzanen KH, Alhakamy M, Al-Namer M, Ahmed F, Tamesh M, Mahdi W, Abdo Z, Mohammed M. Effectiveness of Ledipasvir-Sofosbuvir 12 Weeks After Hepatitis C Virus Genotype 1 Infection and the Factors Associated With Sustained Virologic Response: A Retrospective Study. Cureus 2024; 16:e68249. [PMID: 39350869 PMCID: PMC11439843 DOI: 10.7759/cureus.68249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/30/2024] [Indexed: 10/04/2024] Open
Abstract
BACKGROUND The combination of ledipasvir and sofosbuvir (LDV/SOF) has been licensed to treat genotype 1 hepatitis C virus infection (HCV) with a 12-week regimen. However, there is scant data from Yemen regarding this combination regimen. Here, we investigate sustained virologic responses (SVR) 12 weeks after HCV treatment with LDV/SOF regimens and the factors that contribute to SVR failure. MATERIAL AND METHOD A retrospective cross-sectional study was conducted at Althora General Hospital in Ibb, Yemen, from June 1, 2019, to October 31, 2022, on 53 cases with HCV genotype 1 infection who received combined therapy of LDV/SOF and completed treatment for 12 weeks. The clinical characteristics and treatment follow-up were obtained from patient medical records. Factors associated with SVR failure were investigated in univariate analysis with odds ratio (OR) and 95% confidence interval (CI). RESULT The mean age was 50 ± 15.3 years, and most cases were female (n=36, 67.9%). Comorbidities were diabetes, hypertension, and fatty liver, which were represented in 12 (22.6%), nine (17.0%), and eight (15.1%) cases, respectively. A total of 13 (24.5%) patients had compensated liver cirrhosis, while the remaining 40 patients (75.5%) were non-cirrhotic healthy individuals. The baseline viral load (HCV RNA) was more than 800000 IU/mL in 21 patients (39.6%). Early virological response (ERV) was achieved in 51 patients (96.2%). After treatment, 46 of the patients (86.8%) achieved SVR at Week 12, while failure occurred in two patients (3.8%) and relapse occurred in five patients (9.4%). Blood liver enzymes, including alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, returned to normal, with statistically significant improvements in non-cirrhotic healthy persons than compensated liver cirrhosis individuals (p= 0.006, 0.006, and 0.010; respectively). Factors associated with SVR failure were older age (OR:1.13; 95% CI: 1.03-1.30, p=0.009), presence of liver cirrhosis (OR: 5.48; 95% CI: 1.04-28.98, p=0.031), having diabetes (OR: 6.33; 95% CI: 1.19-37.93, p= 0.019), baseline higher viral load (OR: 2.27; 95% CI: 0.45-12.73, p<0.001), and not achieving EVR (OR:7.63; 95% CI: 3.77- 17.78, p= 0.009). CONCLUSION In this study, we found that LDV/SOF regimens are effective against HCV genotype one infection, allowing for the expansion of 12-week treatment for suitable patients in clinical settings. Additionally, older age, liver cirrhosis, diabetes, higher pretreatment viral load, and non-completion of EVR were associated with SVR failure. However, due to the small number of HCV genotype 1 infected individuals in this study, more corporate data is required to get a clear conclusion.
Collapse
Affiliation(s)
| | | | | | - Basheer Abdo
- Internal Medicine, School of Medicine, Ibb University, Ibb, YEM
| | | | | | - Mamoon Al-Namer
- Internal Medicine, School of Medicine, Ibb University, Ibb, YEM
| | - Faisal Ahmed
- Urology, School of Medicine, Ibb University, Ibb, YEM
| | - Munther Tamesh
- Pharmacy, University of Science and Technology, Ibb, YEM
| | - Wadhah Mahdi
- Pharmacy, University of Science and Technology, Ibb, YEM
| | - Zeyad Abdo
- Pharmacy, University of Science and Technology, Ibb, YEM
| | - Marwa Mohammed
- General Practice, School of Medicine, Ibb University, Ibb, YEM
| |
Collapse
|
|
9
|
Park Y, Na SK, Yoon JH, Kim SE, Park JW, Kim GA, Lee HY, Lee YS, Kim JH. Prognosis Following Sustained Virologic Response in Korean Chronic Hepatitis C Patients Treated with Sofosbuvir-Based Treatment: Data from a Multicenter Prospective Observational Study up to 7 Years. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1132. [PMID: 39064561 PMCID: PMC11279039 DOI: 10.3390/medicina60071132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 07/08/2024] [Accepted: 07/12/2024] [Indexed: 07/28/2024]
Abstract
Background and Objectives: Chronic hepatitis C (CHC) can be cured with direct-acting antiviral (DAA) therapy. In Korea, sofosbuvir (SOF) and ledipasvir (LDV)/SOF were launched in 2016. Patients who achieve a sustained virologic response (SVR) following DAA treatment are predicted to have a favorable prognosis. Nevertheless, little is known regarding the prognosis of Korean CHC patients who receive SOF-based treatment and achieve SVR. Therefore, the purpose of this study was to look into the long-term outcomes for these patients. Materials and Methods: This was a prospective, multicenter observational study. CHC patients were enrolled who, following SOF or LDV/SOF treatment, had achieved SVR. The last day for follow-up was December 2023. The primary endpoint was HCC occurrence, which was checked at least once per year. Results: A total of 516 patients were included in this analysis, with a median follow-up duration of 39.0 months. Among them, 231 were male patients (44.8%), with a median age of 62.0 years. Genotypes were 1 (90, 17.4%), 2 (423, 82.0%), and 3 (3, 0.6%). The combination of SOF plus ribavirin was the most common treatment (394, 76.4%). In total, 160 patients were cirrhotic (31.0%), and the mean Child-Pugh score was 5.1. Within a maximum of 7 years, 21 patients (4.1%) developed HCC. Patients with HCC were older (69 vs. 61 years, p = 0.013) and had a higher cirrhosis incidence (81.0 vs. 28.9%, p < 0.001), higher AFP (6.0 vs. 3.3, p = 0.003) and higher APRI (0.8 vs. 0.5, p = 0.005). Age over 65 (p = 0.016) and cirrhosis (p = 0.005) were found to be significant risk factors for HCC by Cox regression analysis. Conclusions: Patients who achieved SVR with SOF-based treatment had a relatively favorable prognosis. However, the risk of HCC was not eliminated, especially in older and cirrhotic patients. Therefore, routine follow-up, surveillance, and early treatment are required.
Collapse
Affiliation(s)
- Yewan Park
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul 02447, Republic of Korea; (Y.P.); (G.-A.K.)
| | - Seong-Kyun Na
- Department of Internal Medicine, Inje University Sanggye Paik Hospital, Seoul 01757, Republic of Korea; (S.-K.N.); (H.-Y.L.)
| | - Jae-Hyun Yoon
- Department of Internal Medicine, School of Medicine, Chonnam National University Hospital, Gwangju 61469, Republic of Korea;
| | - Sung-Eun Kim
- Department of Internal Medicine, Hallym University College of Medicine, Anyang 14068, Republic of Korea; (S.-E.K.); (J.-W.P.)
| | - Ji-Won Park
- Department of Internal Medicine, Hallym University College of Medicine, Anyang 14068, Republic of Korea; (S.-E.K.); (J.-W.P.)
| | - Gi-Ae Kim
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul 02447, Republic of Korea; (Y.P.); (G.-A.K.)
| | - Hyo-Young Lee
- Department of Internal Medicine, Inje University Sanggye Paik Hospital, Seoul 01757, Republic of Korea; (S.-K.N.); (H.-Y.L.)
| | - Young-Sun Lee
- Department of Internal Medicine, Korea University Medical Center, Seoul 08308, Republic of Korea;
| | - Jeong-Han Kim
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul 05030, Republic of Korea
- Research Institute of Medical Science, Konkuk University School of Medicine, Seoul 05029, Republic of Korea
| |
Collapse
|
|
10
|
Sallam M, Khalil R. Contemporary Insights into Hepatitis C Virus: A Comprehensive Review. Microorganisms 2024; 12:1035. [PMID: 38930417 PMCID: PMC11205832 DOI: 10.3390/microorganisms12061035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 05/15/2024] [Accepted: 05/20/2024] [Indexed: 06/28/2024] Open
Abstract
Hepatitis C virus (HCV) remains a significant global health challenge. Approximately 50 million people were living with chronic hepatitis C based on the World Health Organization as of 2024, contributing extensively to global morbidity and mortality. The advent and approval of several direct-acting antiviral (DAA) regimens significantly improved HCV treatment, offering potentially high rates of cure for chronic hepatitis C. However, the promising aim of eventual HCV eradication remains challenging. Key challenges include the variability in DAA access across different regions, slightly variable response rates to DAAs across diverse patient populations and HCV genotypes/subtypes, and the emergence of resistance-associated substitutions (RASs), potentially conferring resistance to DAAs. Therefore, periodic reassessment of current HCV knowledge is needed. An up-to-date review on HCV is also necessitated based on the observed shifts in HCV epidemiological trends, continuous development and approval of therapeutic strategies, and changes in public health policies. Thus, the current comprehensive review aimed to integrate the latest knowledge on the epidemiology, pathophysiology, diagnostic approaches, treatment options and preventive strategies for HCV, with a particular focus on the current challenges associated with RASs and ongoing efforts in vaccine development. This review sought to provide healthcare professionals, researchers, and policymakers with the necessary insights to address the HCV burden more effectively. We aimed to highlight the progress made in managing and preventing HCV infection and to highlight the persistent barriers challenging the prevention of HCV infection. The overarching goal was to align with global health objectives towards reducing the burden of chronic hepatitis, aiming for its eventual elimination as a public health threat by 2030.
Collapse
Affiliation(s)
- Malik Sallam
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan
- Department of Clinical Laboratories and Forensic Medicine, Jordan University Hospital, Amman 11942, Jordan
| | - Roaa Khalil
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan
| |
Collapse
|
|
11
|
Basyte-Bacevice V, Kupcinskas L. Viral Hepatitis C: From Unraveling the Nature of Disease to Cure and Global Elimination. Dig Dis 2024; 42:486-495. [PMID: 38718765 DOI: 10.1159/000539210] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 04/23/2024] [Indexed: 06/13/2024]
Abstract
BACKGROUND The discovery of the hepatitis C virus (HCV) and direct-acting antiviral (DAA) drugs is one of the major milestones in the last 3 decades of medicine. These discoveries encouraged the World Health Organization (WHO) to set an ambitious goal to eliminate HCV by 2030, meaning "a 90% reduction in new cases of chronic HCV, a 65% reduction in HCV deaths, and treatment of 80% of eligible people with HCV infections." SUMMARY This review summarizes the key achievements from the discovery of HCV to the development of effective treatment and global elimination strategies. A better understanding of HCV structure, enzymes, and lifecycle led to the introduction of new drug targets and the discovery of DAA. Massive public health interventions are required, such as screening, access to care, treatment, and post-care follow-up, to make the most of DAA's potential. Screening must be supported by fast, accessible, sensitive, specific HCV diagnostic tests and noninvasive methods to determine the stage of liver disease. Linkage to care and treatment access are critical components of a comprehensive HCV elimination program, and decentralization plays a key role in ensuring their effectiveness. KEY MESSAGES Effective and simple screening strategies, rapid diagnostic tools, linkage to health care, and accessible treatment are key elements to achieving the WHO's goal. Incorporating treatment as prevention strategies into elimination programs together with preventive education and harm reduction interventions can have a profound and lasting impact on reducing both the incidence and prevalence of HCV. However, WHO's goal can be challenging to implement because of the need for high financial resources and strong political commitment.
Collapse
Affiliation(s)
| | - Limas Kupcinskas
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| |
Collapse
|
|
12
|
Dobrowolska K, Brzdęk M, Rzymski P, Flisiak R, Pawłowska M, Janczura J, Brzdęk K, Zarębska-Michaluk D. Revolutionizing hepatitis C treatment: next-gen direct-acting antivirals. Expert Opin Pharmacother 2024; 25:833-852. [PMID: 38768013 DOI: 10.1080/14656566.2024.2358139] [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] [Received: 04/11/2024] [Accepted: 05/17/2024] [Indexed: 05/22/2024]
Abstract
INTRODUCTION With the introduction of highly effective and safe therapies with next-generation direct-acting antivirals (DAAs), that act without interferon, hepatitis C virus (HCV) infection remains the only treatable chronic infectious disease. AREAS COVERED The review aims to provide an overview of the therapy revolution with a description of specific DAAs, their mechanisms of action, a summary of the safety and efficacy of specific regimens, and a discussion of populations requiring special therapeutic approaches. EXPERT OPINION DAAs are highly effective, safe, and easy to use. However, challenges such as access to health services and loss of patients from the cascade of care, especially in groups disproportionately affected by HCV infection, such as substance abusers, make it difficult to achieve the WHO's goal of HCV elimination. The proposed strategy to combat these difficulties involves a one-step approach to diagnosing and treating the infection, the availability of long-lasting forms of medication, and the development of an effective vaccine. The aforementioned opportunities are all the more important as the world is facing an opioid epidemic that is translating into an increase in HCV prevalence. This phenomenon is of greatest concern in women of childbearing age and in those already pregnant due to treatment limitations.
Collapse
Affiliation(s)
| | - Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
| | - Piotr Rzymski
- Department of Environmental Medicine, Poznan University of Medical Sciences, Poznan, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
| | - Małgorzata Pawłowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland
| | - Jakub Janczura
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
| | - Kinga Brzdęk
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
| | | |
Collapse
|
|
13
|
Indolfi G, Gonzalez-Peralta RP, Jonas MM, Sayed MHE, Fischler B, Sokal E, Wirth S, Nicastro E. ESPGHAN recommendations on treatment of chronic hepatitis C virus infection in adolescents and children including those living in resource-limited settings. J Pediatr Gastroenterol Nutr 2024; 78:957-972. [PMID: 38369891 DOI: 10.1002/jpn3.12160] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 08/29/2023] [Accepted: 10/25/2023] [Indexed: 02/20/2024]
Abstract
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide, with more than three million viraemic adolescents and children. Treatment of adults with HCV infection and HCV-related liver disease has advanced considerably thanks to development and improvements in therapy. Direct-acting antiviral regimens are safe and effective. Three regimens with pangenotypic activity (glecaprevir/pibrentasvir, sofosbuvir/velpatasvir and sofosbuvir/velpatasvir/voxilaprevir) and three regimens with genotype-specific activity (sofosbuvir/ribavirin, sofosbuvir/ledipasvir and elbasvir/grazoprevir) have been approved with age-specific limitation for treatment of children with chronic hepatitis C by the European Medicines Agency and the United States Food and Drug Administration. The World Health Organization has set the ambitious target to eliminate hepatitis C as a major public health threat by 2030 and based its actions against HCV on the large use of direct acting antivirals. These updated European Society for Pediatric Gastroenterology, Hepatology and Nutrition recommendations on treatment of hepatitis C describe the optimal therapeutic management of adolescents and children with HCV infection including specific indications for those living in resource-limited settings.
Collapse
Affiliation(s)
- Giuseppe Indolfi
- Department NEUROFARBA University of Florence, Florence, Italy
- Paediatric and Liver Unit, Meyer Children's Hospital IRCCS, Firenze, Italy
| | - Regino P Gonzalez-Peralta
- Pediatric Gastroenterology, Hepatology and Liver Transplant, AdventHealth for Children, AdventHealth Transplant Institute, Orlando, Florida, USA
| | | | - Manal Hamdy-El Sayed
- Department of Paediatrics, Children's Hospital, Ain Shams University, Cairo, Egypt
| | - Björn Fischler
- Department of Paediatrics, Karolinska University Hospital, CLINTEC, Karolinska Institutet, Stockholm, Sweden
| | - Etienne Sokal
- UCLouvain, Cliniques Universitaires St Luc, Pediatric Hepatology, Brussels, Belgium
| | - Stefan Wirth
- Department of Paediatrics, Helios University Hospital Wuppertal, Witten-Herdecke University, Germany
| | - Emanuele Nicastro
- Pediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy
| |
Collapse
|
|
14
|
Tuan J, Okoli A, Ogbuagu O. Pharmacokinetic evaluation of sofosbuvir/velpatasvir for the treatment of Chronic Hepatitis C in pediatrics aged 3 and older. Expert Opin Drug Metab Toxicol 2023; 19:881-888. [PMID: 38058292 DOI: 10.1080/17425255.2023.2292736] [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] [Received: 05/12/2023] [Accepted: 12/05/2023] [Indexed: 12/08/2023]
Abstract
INTRODUCTION The World Health Organization proposed targets to eliminate hepatitis C virus (HCV) by 2030, aiming to treat ≥80% of people with HCV, decreasing new chronic infections by 90% and liver-related mortality by 65%. While children/adolescents represent a minority of cases, the true burden is underestimated. Advances in drug development have resulted in simplified treatments that are well-tolerated, effective, and pangenotypic in activity. Sofosbuvir/velpatasvir, a combined nucleotide analog NS5B polymerase inhibitor and NS5A inhibitor, respectively, is approved for HCV treatment for individuals ≥3 years, supported by safety data using lower-dose, novel formulations. AREAS COVERED This review discusses chemistry, pharmacokinetics/pharmacodynamics, dosing, efficacy, and safety of sofosbuvir/velpatasvir highlighting pediatric data. Literature review included publications/conference abstracts from PubMed, Google, and Google Scholar. Information from key clinical trials/regulatory approvals is reviewed. EXPERT OPINION Sofosbuvir/velpatasvir is a safe and effective therapy for the treatment of pangenotypic chronic HCV infection with limited cases of virologic relapse and adverse events among pediatric populations aged 3 years and older. However, the tolerability among children less than 6 years could be improved by alternative formulations, if not, shorter treatment durations. An aspirational role of direct-acting antivirals (DAAs) that should be explored is for the prevention of infection in exposed and at-risk pediatric populations.
Collapse
Affiliation(s)
- Jessica Tuan
- Yale School of Medicine, Department of Internal Medicine, Section of Infectious Diseases, New Haven, CT, USA
- Yale AIDS Program, 135 College St, New Haven, CT, USA
| | - Adaora Okoli
- Yale School of Medicine, Department of Internal Medicine, Section of Infectious Diseases, New Haven, CT, USA
| | - Onyema Ogbuagu
- Yale School of Medicine, Department of Internal Medicine, Section of Infectious Diseases, New Haven, CT, USA
- Yale AIDS Program, 135 College St, New Haven, CT, USA
| |
Collapse
|
|
15
|
Bi W, Kraft A, Engelskircher S, Mischke J, Witte M, Klawonn F, van Ham M, Cornberg M, Wedemeyer H, Hengst J, Jänsch L. Proteomics reveals a global phenotypic shift of NK cells in HCV patients treated with direct-acting antivirals. Eur J Immunol 2023; 53:e2250291. [PMID: 37515498 DOI: 10.1002/eji.202250291] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 07/28/2023] [Accepted: 07/28/2023] [Indexed: 07/31/2023]
Abstract
Chronic hepatitis C virus (HCV) infections compromise natural killer (NK)-cell immunity. Direct-acting antivirals (DAA) effectively eliminate HCV, but the long-term effects on NK cells in cured patients are debated. We conducted a proteomic study on CD56+ NK cells of chronic HCV-infected patients before and 1 year after DAA therapy. Donor-variation was observed in NK-cell proteomes of HCV-infected patients, with 46 dysregulated proteins restored after DAA therapy. However, 30% of the CD56+ NK-cell proteome remained altered 1 year post-therapy, indicating a phenotypic shift with low donor-variation. NK cells from virus-negative cured patients exhibited global regulation of RNA-processing and pathways related to "stimuli response", "chemokine signaling", and "cytotoxicity regulation". Proteomics identified downregulation of vesicle transport components (CD107a, COPI/II complexes) and altered receptor expression profiles, indicating an inhibited NK-cell phenotype. Yet, activated NK cells from HCV patients before and after therapy effectively upregulated IFN-γ and recruited CD107a. Conversely, reduced surface expression levels of Tim-3 and 2B4 were observed before and after therapy. In conclusion, this study reveals long-term effects on the CD56+ NK-cell compartment in convalescent HCV patients 1 year after therapy, with limited abundance of vesicle transport complexes and surface receptors, associated with a responsive NK-cell phenotype.
Collapse
Affiliation(s)
- Wenjie Bi
- Key Laboratory of Infection and Immunity of Shandong Province & Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, P. R. China
- Cellular Proteome Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany
| | - Anke Kraft
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School (MHH), Hannover, Germany
- Centre for Individualised Infection Medicine (CiiM), A Joint Venture Between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany
- German Centre for Infection Research (DZIF), Partner site Hannover-Braunschweig, Hannover, Germany
- TWINCORE, A Joint Venture Between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany
| | - Sophie Engelskircher
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School (MHH), Hannover, Germany
- Centre for Individualised Infection Medicine (CiiM), A Joint Venture Between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany
| | - Jasmin Mischke
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School (MHH), Hannover, Germany
- Centre for Individualised Infection Medicine (CiiM), A Joint Venture Between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany
- German Centre for Infection Research (DZIF), Partner site Hannover-Braunschweig, Hannover, Germany
- TWINCORE, A Joint Venture Between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany
| | - Moana Witte
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School (MHH), Hannover, Germany
- Centre for Individualised Infection Medicine (CiiM), A Joint Venture Between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany
| | - Frank Klawonn
- Cellular Proteome Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany
- Department of Computer Science, Ostfalia University, Wolfenbüttel, Germany
| | - Marco van Ham
- Cellular Proteome Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School (MHH), Hannover, Germany
- Centre for Individualised Infection Medicine (CiiM), A Joint Venture Between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany
- German Centre for Infection Research (DZIF), Partner site Hannover-Braunschweig, Hannover, Germany
- TWINCORE, A Joint Venture Between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany
| | - Heiner Wedemeyer
- Centre for Individualised Infection Medicine (CiiM), A Joint Venture Between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany
- German Centre for Infection Research (DZIF), Partner site Hannover-Braunschweig, Hannover, Germany
- Cluster of Excellence Resolving Infection Susceptibility (RESIST; EXC 2155), Hannover Medical School, Hannover, Germany
| | - Julia Hengst
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School (MHH), Hannover, Germany
| | - Lothar Jänsch
- Cellular Proteome Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany
| |
Collapse
|
|
16
|
Wang W, Chen C, Re VL, Chang SH, Wilson DL, Park H. Association between treatment of hepatitis C virus and risk of cardiovascular disease among insured patients with the virus in the United States. Pharmacoepidemiol Drug Saf 2023; 32:1142-1151. [PMID: 37278688 PMCID: PMC10655016 DOI: 10.1002/pds.5651] [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: 10/03/2022] [Revised: 05/03/2023] [Accepted: 05/25/2023] [Indexed: 06/07/2023]
Abstract
PURPOSE Hepatitis C virus (HCV) infection has been associated with increased risk of cardiovascular disease (CVD). It is unclear whether HCV treatment affects risk of CVD among patients infected with HCV. We assessed the incidence and risk of CVD among insured patients with HCV infection and evaluated if HCV treatment was associated with reduced CVD risk. METHODS This retrospective cohort study used MarketScan Commercial and Medicare Supplement databases. Patients newly diagnosed with HCV (vs. patients without HCV) between January 2008 and August 2015 were categorized by treatment (none, insufficient, or minimum effective) based on receipt and duration of anti-HCV treatments. After propensity score matching, time-dependent Cox proportional hazards models were used to compare CVD risk between patients with HCV versus without and between patients with HCV by treatment type and duration. RESULTS HCV was associated with 13% increased risk of developing CVD overall (adjusted hazard ratio [aHR] 95% CI 1.26-1.35) and with 13% (aHR 1.07-1,18), 9% (aHR 1.03-1.15), and 32% (aHR 1.24-1.40) significantly increased risks of developing coronary artery disease, cerebrovascular disease, and peripheral vascular disease, respectively. Among patients with HCV, compared with no treatment, receipt of minimum effective treatment was associated with 24% decreased risk of CVD, and receipt of insufficient treatment was associated with 14% decreased risk of CVD. CONCLUSIONS Individuals chronically infected with HCV had a higher incidence of CVD. Among patients with HCV, receipt of antiviral treatment for HCV was associated with decreased risk of CVD.
Collapse
Affiliation(s)
- Wei Wang
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida
- Merck & Co., Inc., Rahway, New Jersey, USA
| | - Chao Chen
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida
- Regeneron, NY, USA
| | - Vincent Lo Re
- Division of Infectious Diseases, Department of Medicine; Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania
| | - Shao-Hsuan Chang
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida
| | - Debbie L. Wilson
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida
| | - Haesuk Park
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida
| |
Collapse
|
|
17
|
Odenwald MA, Roth HF, Reticker A, Segovia M, Pillai A. Evolving challenges with long-term care of liver transplant recipients. Clin Transplant 2023; 37:e15085. [PMID: 37545440 DOI: 10.1111/ctr.15085] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 07/17/2023] [Accepted: 07/23/2023] [Indexed: 08/08/2023]
Abstract
The number of liver transplants (LT) performed worldwide continues to rise, and LT recipients are living longer post-transplant. This has led to an increasing number of LT recipients requiring lifelong care. Optimal care post-LT requires careful attention to both the allograft and systemic issues that are more common after organ transplantation. Common causes of allograft dysfunction include rejection, biliary complications, and primary disease recurrence. While immunosuppression prevents rejection and reduces incidences of some primary disease recurrence, it has detrimental systemic effects. Most commonly, these include increased incidences of metabolic syndrome, various malignancies, and infections. Therefore, it is of utmost importance to optimize immunosuppression regimens to prevent allograft dysfunction while also decreasing the risk of systemic complications. Institutional protocols to screen for systemic disease and heightened clinical suspicion also play an important role in providing optimal long-term post-LT care. In this review, we discuss these common complications of LT as well as unique considerations when caring for LT recipients in the years after transplant.
Collapse
Affiliation(s)
- Matthew A Odenwald
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, USA
| | - Hannah F Roth
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, USA
| | - Anesia Reticker
- Department of Pharmacy, University of Chicago Medicine, Chicago, USA
| | - Maria Segovia
- Department of Medicine, Section of Gastroenterology, Duke University School of Medicine, Durham, USA
| | - Anjana Pillai
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, USA
| |
Collapse
|
|
18
|
Cartwright EJ, Pierret C, Minassian C, Esserman DA, Tate JP, Goetz MB, Bhattacharya D, Fiellin DA, Justice AC, Lo Re V, Rentsch CT. Alcohol Use and Sustained Virologic Response to Hepatitis C Virus Direct-Acting Antiviral Therapy. JAMA Netw Open 2023; 6:e2335715. [PMID: 37751206 PMCID: PMC10523171 DOI: 10.1001/jamanetworkopen.2023.35715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Accepted: 08/21/2023] [Indexed: 09/27/2023] Open
Abstract
Importance Some payers and clinicians require alcohol abstinence to receive direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection. Objective To evaluate whether alcohol use at DAA treatment initiation is associated with decreased likelihood of sustained virologic response (SVR). Design, Setting, and Participants This retrospective cohort study used electronic health records from the US Department of Veterans Affairs (VA), the largest integrated national health care system that provides unrestricted access to HCV treatment. Participants included all patients born between 1945 and 1965 who were dispensed DAA therapy between January 1, 2014, and June 30, 2018. Data analysis was completed in November 2020 with updated sensitivity analyses performed in 2023. Exposure Alcohol use categories were generated using responses to the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses for alcohol use disorder (AUD): abstinent without history of AUD, abstinent with history of AUD, lower-risk consumption, moderate-risk consumption, and high-risk consumption or AUD. Main Outcomes and Measures The primary outcome was SVR, which was defined as undetectable HCV RNA for 12 weeks or longer after completion of DAA therapy. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% CIs of SVR associated with alcohol category. Results Among 69 229 patients who initiated DAA therapy (mean [SD] age, 62.6 [4.5] years; 67 150 men [97.0%]; 34 655 non-Hispanic White individuals [50.1%]; 28 094 non-Hispanic Black individuals [40.6%]; 58 477 individuals [84.5%] with HCV genotype 1), 65 355 (94.4%) achieved SVR. A total of 32 290 individuals (46.6%) were abstinent without AUD, 9192 (13.3%) were abstinent with AUD, 13 415 (19.4%) had lower-risk consumption, 3117 (4.5%) had moderate-risk consumption, and 11 215 (16.2%) had high-risk consumption or AUD. After adjustment for potential confounding variables, there was no difference in SVR across alcohol use categories, even for patients with high-risk consumption or AUD (OR, 0.95; 95% CI, 0.85-1.07). There was no evidence of interaction by stage of hepatic fibrosis measured by fibrosis-4 score (P for interaction = .30). Conclusions and Relevance In this cohort study, alcohol use and AUD were not associated with lower odds of SVR. Restricting access to DAA therapy according to alcohol use creates an unnecessary barrier to patients and challenges HCV elimination goals.
Collapse
Affiliation(s)
- Emily J. Cartwright
- Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia
- Atlanta Veterans Affairs Medical Center, Decatur, Georgia
| | - Chloe Pierret
- Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom
| | - Caroline Minassian
- Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom
| | - Denise A. Esserman
- Veterans Affairs Connecticut Healthcare System, US Department of Veterans Affairs, West Haven
| | - Janet P. Tate
- Veterans Affairs Connecticut Healthcare System, US Department of Veterans Affairs, West Haven
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
| | - Matthew B. Goetz
- Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles
- Veterans Affairs Greater Los Angeles Health Care System, US Department of Veterans Affairs, Los Angeles, California
| | - Debika Bhattacharya
- Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles
- Veterans Affairs Greater Los Angeles Health Care System, US Department of Veterans Affairs, Los Angeles, California
| | - David A. Fiellin
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- Yale Program in Addiction Medicine, Yale School of Medicine, New Haven, Connecticut
- Yale School of Public Health, New Haven, Connecticut
| | - Amy C. Justice
- Veterans Affairs Connecticut Healthcare System, US Department of Veterans Affairs, West Haven
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- Yale Program in Addiction Medicine, Yale School of Medicine, New Haven, Connecticut
- Yale School of Public Health, New Haven, Connecticut
| | - Vincent Lo Re
- Division of Infectious Diseases, Department of Medicine and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia
| | - Christopher T. Rentsch
- Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom
- Veterans Affairs Connecticut Healthcare System, US Department of Veterans Affairs, West Haven
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
| |
Collapse
|
|
19
|
O'Brien TR, Lee MH, Wilson E, Kottilil S. IFNL4 Genotype Frequencies in Asian Populations Support Shorter Duration Therapy with Sofosbuvir-Based Hepatitis C Virus Regimens to Increase the Number Cured. J Interferon Cytokine Res 2023; 43:435-438. [PMID: 37347978 PMCID: PMC10517314 DOI: 10.1089/jir.2023.0022] [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] [Received: 02/16/2023] [Accepted: 03/25/2023] [Indexed: 06/24/2023] Open
Abstract
Globally, ∼56.8 million people are chronically infected with hepatitis C virus (HCV), with about half residing in Asia. The cost and efficiency of delivering regimens based on direct-acting antiviral agents for HCV are important considerations in implementing these curative treatments. For sofosbuvir-based regimens, most patients are treated for 12 weeks; however, treatment for 8 weeks has been shown to cure HCV infection in 95% of patients without cirrhosis. Furthermore, virological failure after 8-week treatment occurs in only 1%-2% of individuals without cirrhosis, who have a favorable IFNL4 genotype, which is present in >50% of South Asians and >80% of East Asians. We propose that sofosbuvir-based treatment for 8 weeks, or perhaps shorter, would yield high response rate regimens in Asian countries and markedly increase the number of patients who could be cured for a given cost of the medication. We propose that a noninferiority trial in an East Asian population be conducted to test this hypothesis.
Collapse
Affiliation(s)
- Thomas R. O'Brien
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
| | - Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
| | - Eleanor Wilson
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Shyam Kottilil
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| |
Collapse
|
|
20
|
Aponte-Meléndez Y, Mateu-Gelabert P, Eckhardt B, Fong C, Padilla A, Trinidad-Martínez W, Maldonado-Rodríguez E, Agront N. Hepatitis C virus care cascade among people who inject drugs in puerto rico: Minimal HCV treatment and substantial barriers to HCV care. DRUG AND ALCOHOL DEPENDENCE REPORTS 2023; 8:100178. [PMID: 37555192 PMCID: PMC10404601 DOI: 10.1016/j.dadr.2023.100178] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Revised: 07/06/2023] [Accepted: 07/07/2023] [Indexed: 08/10/2023]
Abstract
Background People who inject drugs (PWID) in Puerto Rico are disproportionately affected by the hepatitis C virus (HCV) epidemic. However, there is a scarcity of data on the HCV care cascade among PWID in Puerto Rico. This study aims to describe the HCV cascade of care among PWID in Puerto Rico, identify gaps, and explore barriers to HCV care. Methods Participants were recruited using respondent-driven sampling and tested for both HCV antibodies (Ab) and RNA (ribonucleic acid) using rapid testing and dried blood spot samples (DBS). The cascade of care was estimated based on the DBS HCV Ab and RNA results, as well as self-reported data on HCV screening, linkage to care, treatment uptake and sustained virologic response collected through a questionnaire. The cascade was constructed sequentially, with each step using the number of people from the preceding step as the base denominator. The survey also assessed participants' perceived barriers to HCV care. Results Out of 150 participants, 126 (84%) had previously been HCV screened, 87% (109/126) were HCV Ab positive, 72% (79/109) were RNA positive,48% (38/79) were linked to care, 32% (12/38) initiated treatment, 58% (7/12) finished treatment, and 71% (5/7) achieved SVR. Barriers to HCV care included concerns about drug abstinence requirements, access to transportation, stigma in healthcare settings, and lack of knowledge about HCV treatment sites. Conclusion This study provides insights into the HCV cascade of care among PWID in Puerto Rico for the first time and highlights limited diagnosis, treatment uptake, and barriers to care.
Collapse
Affiliation(s)
- Yesenia Aponte-Meléndez
- CUNY Graduate School of Public Health and Health Policy, Institute for Implementation Science in Population Health(ISPH) 55 West 125th street, New York, NY 10027,USA
- NYU Rory Meyers College of Nursing 433 1st Ave., New York, NY 10010
| | - Pedro Mateu-Gelabert
- CUNY Graduate School of Public Health and Health Policy, Institute for Implementation Science in Population Health(ISPH) 55 West 125th street, New York, NY 10027,USA
| | - Benjamin Eckhardt
- New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA
| | - Chunki Fong
- CUNY Graduate School of Public Health and Health Policy, Institute for Implementation Science in Population Health(ISPH) 55 West 125th street, New York, NY 10027,USA
| | - Adriana Padilla
- CUNY Graduate School of Public Health and Health Policy, Institute for Implementation Science in Population Health(ISPH) 55 West 125th street, New York, NY 10027,USA
| | - Wanda Trinidad-Martínez
- CUNY Graduate School of Public Health and Health Policy, Institute for Implementation Science in Population Health(ISPH) 55 West 125th street, New York, NY 10027,USA
| | - Eric Maldonado-Rodríguez
- CUNY Graduate School of Public Health and Health Policy, Institute for Implementation Science in Population Health(ISPH) 55 West 125th street, New York, NY 10027,USA
| | - Nancy Agront
- AbbVie Corp., Paseo Caribe Building Suite 22415 Ave Munoz Rivera San Juan, 00901, Puerto Rico
| |
Collapse
|
|
21
|
Sachithanandham J, Balagopal A, Leep-Lazar J, Quinn J, Bowden K, Ward K, Ribeiro RM, Sulkowski MS. Second-Phase Hepatitis C Plasma Viral Kinetics Directly Reflects Reduced Intrahepatic Burden of Hepatitis C Virus. J Infect Dis 2023; 228:311-320. [PMID: 36722133 PMCID: PMC10420397 DOI: 10.1093/infdis/jiad025] [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: 10/04/2022] [Revised: 01/20/2023] [Accepted: 01/26/2023] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Mathematical models explain how antivirals control viral infections. Hepatitis C virus (HCV) treatment results in at least 2 phases of decline in viremia. The first phase reflects clearance of rapidly produced virions. The second phase is hypothesized to derive from loss of infected cells but has been challenging to prove. METHODS Using single-cell methods, we quantified the number of hepatitis C virus (HCV)-infected hepatocytes in liver biopsies taken before and within 7 days of initiating direct-acting antivirals (DAAs) in a double-blinded randomized controlled trial testing 2 (sofosbuvir-velpatasvir) versus 3 (sofosbuvir-velpatasvir-voxilaprevir) DAAs. RESULTS We employed thousands of intrahepatic measurements in 10 persons with chronic genotype 1a HCV infection: median proportion of infected hepatocytes declined from 11.3% (range, 1.3%-59%) to 0.6% (range, <0.3%-5.8%), a loss of 75%-95% infected hepatocytes. Plasma viremia correlated with numbers of HCV-infected hepatocytes (r = 0.77; P < .0001). Second-phase plasma dynamics and changes in infected hepatocytes were indistinct (P = .16), demonstrating that second-phase viral dynamics derive from loss of infected cells. DAAs led to a decline in intracellular HCV RNA and interferon-stimulated gene expression (P < .05 for both). CONCLUSIONS We proved that second-phase viral dynamics reflect decay of intrahepatic burden of HCV, partly due to clearance of HCV RNA from hepatocytes. CLINICAL TRIALS REGISTRATION NCT02938013.
Collapse
Affiliation(s)
- Jaiprasath Sachithanandham
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University School of Public Health, Baltimore, Maryland, USA
| | - Ashwin Balagopal
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Julia Leep-Lazar
- Lewis Katz School of Medicine, Temple University,Philadelphia, Pennsylvania, USA
| | - Jeffrey Quinn
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Kenneth Bowden
- Applied Physics Laboratory, Johns Hopkins University, Laurel, Maryland, USA
| | - Kathleen Ward
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Ruy M Ribeiro
- Los Alamos National Laboratory, Los Alamos, New Mexico, USA
| | - Mark S Sulkowski
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| |
Collapse
|
|
22
|
Sharma P, Sawtell R, Wang Q, Sise ME. Management of Hepatitis C Virus and Hepatitis B Virus Infection in the Setting of Kidney Disease. ADVANCES IN KIDNEY DISEASE AND HEALTH 2023; 30:343-355. [PMID: 37657881 PMCID: PMC10479952 DOI: 10.1053/j.akdh.2023.04.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 04/04/2023] [Accepted: 04/19/2023] [Indexed: 09/03/2023]
Abstract
Treatment of chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection poses unique challenges in patients with kidney disease. Direct-acting antivirals have been a major breakthrough in eradicating HCV infection, and several pangenotypic regimens are available for patients with chronic kidney disease or end-stage kidney disease requiring dialysis with high cure rates and no need for dose adjustment. Direct-acting antiviral therapy alone can treat HCV-associated cryoglobulinemic glomerulonephritis; concurrent antiviral and immunosuppressive therapy is needed for cases of severe, organ-threatening manifestations of cryoglobulinemia. Immunosuppression may be needed for HBV-associated kidney disease (polyarteritis nodosa or membranous nephropathy) when there is evidence of severe immune-mediated injury while weighing the risk of potential viral activation. Most HBV antiviral agents need to be dose-adjusted in patients with chronic kidney disease or end-stage kidney disease requiring dialysis, and drug-drug interactions need to be carefully evaluated in patients with kidney transplants. Considerations for accepting HCV- and HBV-infected donors for kidney transplantation are discussed.
Collapse
Affiliation(s)
- Purva Sharma
- Department of Medicine, Division of Nephrology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell; Glomerular Disease Center at Northwell Health, Hempstead, NY
| | - Rani Sawtell
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA
| | - Qiyu Wang
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA
| | - Meghan E Sise
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA.
| |
Collapse
|
|
23
|
Brzdęk M, Zarębska-Michaluk D, Invernizzi F, Cilla M, Dobrowolska K, Flisiak R. Decade of optimizing therapy with direct-acting antiviral drugs and the changing profile of patients with chronic hepatitis C. World J Gastroenterol 2023; 29:949-966. [PMID: 36844142 PMCID: PMC9950869 DOI: 10.3748/wjg.v29.i6.949] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/22/2022] [Accepted: 01/09/2023] [Indexed: 02/10/2023] Open
Abstract
Chronic infection with the hepatitis C virus (HCV) remains a major health problem affecting approximately 58 million people worldwide. In the era of interferon (IFN)-based regimens, patients particularly infected with genotypes 1 and 4 achieved a low response rate. The implementation of direct-acting antivirals changed the landscape of HCV treatment. The increase in effectiveness provided us with the hope of eliminating HCV as a significant public threat by 2030. In the following years, there was an observed improvement in the treatment of HCV with genotype-specific regimens and highly effective pangenotypic options that are the most recent stage of the revolution. The optimization of therapy was accompanied by changes in the patient profile from the beginning of the IFN-free era over time. Patients treated with antiviral therapies were younger in successive periods, less burdened with comorbidities and comedications, more frequently treatment-naïve and had less advanced liver disease. Before the IFN-free era, specific subpopulations such as patients with HCV/HIV coinfection, those with a history of previous treatment, patients with renal impairment or with cirrhosis had lower chances for a virologic response. Currently, these populations should no longer be considered difficult to treat. Despite the high effectiveness of HCV therapy, there is a small percentage of patients with treatment failure. However, they can be effectively retreated with pangenotypic rescue regimens.
Collapse
Affiliation(s)
- Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, Kielce 25-516, Poland
| | | | - Federica Invernizzi
- Center for Liver Disease, Division of Internal Medicine and Hepatology, IRCCS Ospedale San Raffaele, Milan 20-132, Italy
| | - Marta Cilla
- Center for Liver Disease, Division of Internal Medicine and Hepatology, IRCCS Ospedale San Raffaele, Milan 20-132, Italy
| | | | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-540, Poland
| |
Collapse
|
|
24
|
Awasthi A, Katiyar H, Rungta S, Deep A, Kumar V, Kumar A, Tiwari P, Goel A. Eight versus twelve weeks of sofosbuvir-velpatasvir in treatment-naïve non-cirrhotic patients with chronic hepatitis C virus infection: Study protocol for a multicentric, open labelled, randomized, non-inferiority trial (RESOLVE trial). PLoS One 2023; 18:e0285725. [PMID: 37200346 DOI: 10.1371/journal.pone.0285725] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 04/25/2023] [Indexed: 05/20/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) is a common cause of liver cirrhosis and hepatocellular carcinoma. Globally, nearly 71 million people have chronic HCV infection, and approximately 399,000 dies annually. In patients without cirrhosis, HCV infection is treated with 12 weeks of sofosbuvir/velpatasvir combination. Results from available small, single-centre observational studies suggest that the sofosbuvir/velpatasvir combination given for 8 weeks may be as effective as the standard 12 weeks of treatment. We propose to compare the treatment response of 12 weeks versus 8 weeks of sofosbuvir/velpatasvir in non-cirrhotic people with chronic HCV infection. METHODS This multicentric, randomized, open-label, non-inferiority trial will include 880 (2 arms x 440) treatment naïve, viraemic (HCV RNA >10,000 IU/mL), non-cirrhotic adults (age >18 years) with chronic hepatitis C. People who are at high-risk for HCV reinfection such as haemophiliacs, people who inject drugs, those on maintenance hemodialysis or having HIV will be excluded. The presence or absence of cirrhosis will be determined with a combination of history, examination, ultrasound, liver stiffness measured with transient elastography, APRI, FIB-4, and esophagogastroduodenoscopy. Participants will be randomized to receive either 8- or 12-week sofosbuvir/velpatasvir treatment. A blood specimen will be collected before starting the treatment (to determine the HCV genotype), after 4 weeks of treatment (for early virological response), and at 12 weeks after treatment discontinuation for SVR12. DISCUSSION The study will provide data on the efficacy of 8 weeks of treatment as compared to the standard of care (12 weeks) in non-cirrhotic patients with chronic HCV infection. Treatment for a shorter duration may improve treatment compliance, reduce the cost of treatment, and ease the treatment implementation from a public health perspective. TRIAL REGISTRATION Registered with Clinical Trial Registry of India (http://ctri.nic.in) Registration No. CTRI/2022/03/041368 [Registered on: 24/03/2022]-Trial Registered Prospectively.
Collapse
Affiliation(s)
- Ashish Awasthi
- Centre for Chronic Disease Control, New Delhi, India
- Centre for Chronic Conditions and, Injuries, Public Health Foundation of India, Gurgaon, India
| | - Harshita Katiyar
- Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Sumit Rungta
- Department of Gastroenterology, King George Medical University, Lucknow, India
| | - Amar Deep
- Department of Gastroenterology, King George Medical University, Lucknow, India
| | - Vinod Kumar
- Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Lucknow, India
| | - Ajay Kumar
- Department of Gastroenterology, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
| | - Prachi Tiwari
- Department of Gastroenterology, King George Medical University, Lucknow, India
| | - Amit Goel
- Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| |
Collapse
|
|
25
|
Merli M, Rattotti S, Spina M, Re F, Motta M, Piazza F, Orsucci L, Ferreri AJ, Perbellini O, Dodero A, Vallisa D, Pulsoni A, Santoro A, Sacchi P, Zuccaro V, Chimienti E, Russo F, Visco C, Zignego AL, Marcheselli L, Passamonti F, Luminari S, Paulli M, Bruno R, Arcaini L. Direct-Acting Antivirals as Primary Treatment for Hepatitis C Virus-Associated Indolent Non-Hodgkin Lymphomas: The BArT Study of the Fondazione Italiana Linfomi. J Clin Oncol 2022; 40:4060-4070. [PMID: 35714311 PMCID: PMC9746784 DOI: 10.1200/jco.22.00668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
PURPOSE We prospectively treated patients with hepatitis C virus (HCV)-associated indolent lymphomas with genotype-appropriate direct-acting antivirals (DAAs) with the aim to evaluate virologic and hematologic outcomes. No prospective studies in this setting have been published so far. METHODS FIL_BArT is a prospective, multicenter, phase II trial that evaluated genotype-appropriate DAAs in untreated HCV-positive patients with indolent lymphomas without criteria for immediate conventional antilymphoma treatment. The primary objective was sustained virologic response, whereas the main secondary objectives were overall response rate of lymphoma and progression-free survival. RESULTS Forty patients were enrolled, including 27 with marginal zone lymphoma. Median age was 68 years. Extranodal sites were involved in 14 cases (35%). Main genotypes were 1 in 16 patients and 2 in 21 patients. All patients received genotype-guided DAAs: 17 ledipasvir/sofosbuvir, eight sofosbuvir plus ribavirin, and 15 sofosbuvir/velpatasvir. All patients achieved sustained virologic response (100%). DAAs were well tolerated, with only two grade 3-4 adverse events. Overall response rate of lymphoma was 45%, including eight patients (20%) achieving complete response and 10 (25%) partial response, whereas 16 exhibited stable disease and six progressed. With a median follow-up of 37 months, two patients died (3-year overall survival 93%; 95% CI, 74 to 98) and three additional patients progressed, with a 3-year progression-free survival of 76% (95% CI, 57 to 87). CONCLUSION HCV eradication by DAAs was achieved in 100% of HCV-positive patients with indolent lymphomas not requiring immediate conventional treatment and resulted in non-negligible rate of lymphoma responses. Treatment with DAAs should be considered as the first-line therapy in this setting.
Collapse
Affiliation(s)
- Michele Merli
- Division of Hematology, University Hospital Ospedale di Circolo e Fondazione Macchi, ASST Sette Laghi, University of Insubria, Varese, Italy
| | - Sara Rattotti
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Michele Spina
- Division of Medical Oncology and Immune-related Tumors, Centro di Riferimento Oncologico IRCCS, Aviano, Italy
| | - Francesca Re
- Division of Hematology and BMT Center, Azienda Ospedaliera Universitaria, Parma, Italy
| | - Marina Motta
- Division of Hematology, ASST Spedali Civili, Brescia, Italy
| | - Francesco Piazza
- Hematology and Clinical Immunology Unit, Department of Medicine—DIMED, University of Padova, Padova, Italy
| | - Lorella Orsucci
- Division of Hematology, Città della Salute e della Scienza di Torino, Torino, Italy
| | | | - Omar Perbellini
- Division of Hematology, San Bortolo Hospital, Vicenza, Italy
| | - Anna Dodero
- Division of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Daniele Vallisa
- Division of Hematology, Ospedale Guglielmo da Saliceto, Piacenza, Italy
| | - Alessandro Pulsoni
- Department of Translational and Precision Medicine, Sapienza University of Roma, Roma, Italy
| | - Armando Santoro
- Department of Biomedical Sciences, Humanitas University, IRCCS Humanitas Research Hospital-Humanitas Cancer Center, Milano, Italy
| | - Paolo Sacchi
- Division of Infectious and Tropical Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Valentina Zuccaro
- Division of Infectious and Tropical Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Emanuela Chimienti
- Division of Medical Oncology and Immune-related Tumors, Centro di Riferimento Oncologico IRCCS, Aviano, Italy
| | - Filomena Russo
- Division of Hematology and BMT Center, Azienda Ospedaliera Universitaria, Parma, Italy
| | - Carlo Visco
- Department of Medicine, Section of Hematology, University of Verona, Verona, Italy
| | - Anna Linda Zignego
- Department of Clinical and Experimental Medicine, Interdepartmental Hepatology Center MASVE, University of Firenze, Firenze, Italy
| | | | - Francesco Passamonti
- Division of Hematology, University Hospital Ospedale di Circolo e Fondazione Macchi, ASST Sette Laghi, University of Insubria, Varese, Italy,Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Stefano Luminari
- Surgical, Medical and Dental Department of Morphological Sciences related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy,Division of Hematology, Azienda Unità Sanitaria Locale-IRCCS, Reggio Emilia, Italy
| | - Marco Paulli
- Unit of Anatomic Pathology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy,Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Raffaele Bruno
- Division of Infectious and Tropical Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy,Department of Clinical, Surgical, Diagnostic, and Paediatric Sciences, University of Pavia, Pavia, Italy
| | - Luca Arcaini
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy,Department of Molecular Medicine, University of Pavia, Pavia, Italy,Luca Arcaini, MD, Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, 27100 Pavia, Italy; e-mail:
| | | |
Collapse
|
|
26
|
Yee LM, Shah SK, Grobman WA, Labellarte PZ, Barrera L, Jhaveri R. Identifying barriers and facilitators of the inclusion of pregnant individuals in hepatitis C treatment programs in the United States. PLoS One 2022; 17:e0277987. [PMID: 36399489 PMCID: PMC9674123 DOI: 10.1371/journal.pone.0277987] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 11/07/2022] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The rising prevalence of hepatitis C virus (HCV) infection and the availability of direct acting antivirals for HCV treatment has prompted a public health goal of HCV eradication. Despite the availability of treatment for HCV, treatment programs have generally excluded pregnant individuals. Our objective was to query patients and clinicians to identify barriers to including pregnant individuals in HCV treatment programs. METHODS AND FINDINGS This qualitative investigation included obstetricians and previously/currently pregnant individuals with HCV. Participants completed interviews regarding knowledge of and attitudes towards HCV treatment and perceived barriers to treatment during pregnancy. Data were analyzed using the constant comparative method. Obstetricians (N = 18) and patients (N = 21) described concerns about equity, access, and cost. Both expressed uncertainty about safety and confirmed a need for clinician education. Obstetricians emphasized the lack of professional guidelines. Although some clinicians expressed concern about patient adherence and engagement, patients were largely desirous of treatment; both groups identified potential benefits of antenatal treatment. CONCLUSIONS Both patients and obstetricians were generally receptive to HCV treatment in pregnancy and recognized pregnancy as an important window of opportunity for treatment. Our findings suggest the need for further research on maternal-fetal safety of HCV treatment as well as on interventions to ensure fair and appropriate access to HCV treatment for pregnant individuals.
Collapse
Affiliation(s)
- Lynn M. Yee
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America
- * E-mail:
| | - Seema K. Shah
- Division of Advanced General Pediatrics, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America
- Smith Child Health Outcomes Research and Evaluation Center, Ann and Robert H. Lurie Children’s Hospital, Chicago, Illinois, United States of America
| | - William A. Grobman
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, The Ohio State University School of Medicine, Columbus, Ohio, United States of America
| | - Patricia Z. Labellarte
- Smith Child Health Outcomes Research and Evaluation Center, Ann and Robert H. Lurie Children’s Hospital, Chicago, Illinois, United States of America
| | - Leonardo Barrera
- Smith Child Health Outcomes Research and Evaluation Center, Ann and Robert H. Lurie Children’s Hospital, Chicago, Illinois, United States of America
| | - Ravi Jhaveri
- Division of Infectious Diseases, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America
| |
Collapse
|
|
27
|
Lee SK, Lee SW, Lee HL, Kim HY, Kim CW, Song DS, Chang UI, Yang JM, Yoo SH, Kwon JH, Nam SW, Kim SH, Song MJ, Lee J, Yang H, Bae SH, Han JW, Nam H, Sung PS, Jang JW, Choi JY, Yoon SK. Real-life experience of ledipasvir and sofosbuvir for HCV infected Korean patients: a multicenter cohort study. Korean J Intern Med 2022; 37:1167-1175. [PMID: 35618302 PMCID: PMC9666263 DOI: 10.3904/kjim.2022.013] [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: 01/06/2022] [Revised: 04/07/2022] [Accepted: 04/20/2022] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND/AIMS To evaluate the efficacy and safety of ledipasvir/sofosbuvir (LDV/SOF) therapy in hepatitis C virus (HCV)-infected Korean patients in a real clinical setting. METHODS A total of 273 patients who received LDV/SOF therapy between May 2016 and February 2021 were consecutively enrolled and analyzed. A per-protocol analysis was performed to evaluate the virologic response. RESULTS Seventy-five percent were infected with genotype 1, and 25% were infected with genotype 2. A hundred eightyone (66.3%) patients had chronic hepatitis, 74 (27.1%) had compensated cirrhosis, eight (2.9%) had decompensated cirrhosis, and 10 (3.7%) had undergone liver transplantation. Undetectable HCV RNA at week 4 was achieved in 90.2% (231/256) of patients, 99.2% (250/252) achieved the end of treatment response, and 98.1% (202/206) achieved sustained virologic response at 12 weeks post-treatment (SVR12). According to liver function, the SVR12 rates were 99.3% (135/136) in chronic hepatitis, 96.4% (53/55) in compensated cirrhosis, and 100% (6/6) in decompensated cirrhosis. The SVR12 rates according to the genotype were 98.2% (167/170) for genotype 1 and 97.2% (35/36) for genotype 2. An 8-week LDV/SOF treatment in treatment-naïve chronic hepatitis patients with HCV RNA < 6,000,000 IU/mL at baseline resulted in 100% (23/23) SVR12 rates. Overall, LDV/SOF was tolerated well, with a 0.7% (2/273) discontinuation rate due to adverse events that were unrelated to LDV/SOF. CONCLUSION LDV/SOF is effective and safe for treating HCV-infected Korean patients with high SVR12 rates.
Collapse
Affiliation(s)
- Soon Kyu Lee
- Division of Hepatology, Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Sung Won Lee
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon,
Korea
| | - Hae Lim Lee
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon,
Korea
| | - Hee Yeon Kim
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon,
Korea
| | - Chang Wook Kim
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu,
Korea
| | - Do Seon Song
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon,
Korea
| | - U Im Chang
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon,
Korea
| | - Jin Mo Yang
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon,
Korea
| | - Sun Hong Yoo
- Division of Hepatology, Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Jung Hyun Kwon
- Division of Hepatology, Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Soon Woo Nam
- Division of Hepatology, Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Seok-Hwan Kim
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon,
Korea
| | - Myeong Jun Song
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon,
Korea
| | - Jaejun Lee
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Hyun Yang
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Si Hyun Bae
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Ji Won Han
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Heechul Nam
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu,
Korea
| | - Pil Soo Sung
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Jeong Won Jang
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Jong Young Choi
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Seung Kew Yoon
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| |
Collapse
|
|
28
|
Hoyt JE, Teja N, Jiang T, Rozema L, Gui J, Watts BV, Shiner B, Gradus JL. Changes in Alcohol Consumption following Direct-Acting Antiviral Treatment for Hepatitis C in VA Patients with Comorbid Alcohol Use Disorder and PTSD. J Dual Diagn 2022; 18:185-198. [PMID: 36151743 PMCID: PMC9719291 DOI: 10.1080/15504263.2022.2123119] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
OBJECTIVE To investigate whether direct-acting antivirals (DAA) for hepatitis C viral infection (HCV): glecaprevir/pibrentasvir (GLE/PIB), ledipasvir/sofosbuvir (LDV/SOF), and sofosbuvir/velpatasvir (SOF/VEL) are associated with reduced alcohol consumption among veterans with alcohol use disorder (AUD) and co-occurring post-traumatic stress disorder (PTSD). METHODS We measured change in Alcohol Use Disorder Identification Test-Consumption Module (AUDIT-C) scores in a retrospective cohort of veterans with PTSD and AUD receiving DAAs for HCV. RESULTS One thousand two hundred and eleven patients were included (GLE/PIB n = 174, LDV/SOF n = 808, SOF/VEL n = 229). Adjusted frequencies of clinically meaningful improvement were 30.5% for GLE/PIB, 45.5% for LDV/SOF, and 40.5% for SOF/VEL. The frequency was lower for GLE/PIB than for LDV/SOF (OR = 0.59; 95% CI [0.40, 0.87]) or SOF/VEL (OR = 0.66; 95% CI [0.42, 1.04]). CONCLUSIONS DAA treatment for HCV was associated with a substantial reduction in alcohol use in patients with AUD and co-occurring PTSD. Further exploration of the role of DAAs in AUD treatment is warranted.
Collapse
Affiliation(s)
- Jessica E Hoyt
- White River Junction Veterans Affairs Medical Center, White River Junction, Vermont, USA
| | - Nikhil Teja
- White River Junction Veterans Affairs Medical Center, White River Junction, Vermont, USA
| | - Tammy Jiang
- Boston University School of Public Health, Boston, Massachusetts, USA
| | - Luke Rozema
- White River Junction Veterans Affairs Medical Center, White River Junction, Vermont, USA
| | - Jiang Gui
- White River Junction Veterans Affairs Medical Center, White River Junction, Vermont, USA
- Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA
| | - Bradley V Watts
- White River Junction Veterans Affairs Medical Center, White River Junction, Vermont, USA
- Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA
| | - Brian Shiner
- White River Junction Veterans Affairs Medical Center, White River Junction, Vermont, USA
- Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA
- Veterans Administration National Center for PTSD, White River Junction, Vermont, USA
| | - Jaimie L Gradus
- Boston University School of Public Health, Boston, Massachusetts, USA
| |
Collapse
|
|
29
|
Long-Term Follow-Up of Thalassemia Major Patients with Hepatitis C Virus Treated with Sofosbuvir and Daclatasvir: A Cohort Study. Arch Med Res 2022; 53:666-672. [DOI: 10.1016/j.arcmed.2022.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 09/01/2022] [Accepted: 09/22/2022] [Indexed: 11/17/2022]
|
|
30
|
Gan PL, Huang S, Pan X, Xia HF, Zeng XY, Ren WS, Zhou X, Lv MH, Tang XW. Global research trends in the field of liver cirrhosis from 2011 to 2020: A visualised and bibliometric study. World J Gastroenterol 2022; 28:4909-4919. [PMID: 36156929 PMCID: PMC9476861 DOI: 10.3748/wjg.v28.i33.4909] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 06/17/2022] [Accepted: 08/06/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Liver cirrhosis is the leading cause of liver-related mortality worldwide. It is currently a global health challenge.
AIM This research intended to explore and analyse research trends and frontiers in this field during the last 10 years, providing new inspiration for clinical decision-making and scientific research.
METHODS Publications on hepatic cirrhosis research were retrieved from the Web of Science Core Collection on April 4, 2021. Bibliometric visualisation was conducted through VOSviewer and CiteSpace.
RESULTS The analytic research was based on original articles and reviews. A total of 7775 records of hepatic cirrhosis published from 2011 to 2020 were retrieved. In the past ten years, the number of related annual publications has increased significantly, especially in the United States and China. All publications were distributed among 109 countries. The United States contributed the most (21.95%) and was consistently the leading driving force, with a solid academic reputation in this area. The University of Barcelona distributed the most related articles (177 articles) and was cited the most frequently. The Journal of Hepatology ranked third in the top 10 journals, which has the highest impact factor (impact factor 2019 = 20.582). Jasmohan S. Bajaj was the most productive author (72 articles). Burst keywords (e.g., sofosbuvir, burden, care, sarcopenia, chronic liver failure, human gut microbiome, and nonalcoholic fatty liver disease) and a succession of reference citation bursts have provided clues about research frontiers in recent years.
CONCLUSION This study identified developing trends in the evolution of liver cirrhosis to provide new inspiration for researchers.
Collapse
Affiliation(s)
- Pei-Ling Gan
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China
- Department of Gastroenterology, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, Sichuan Province, China
| | - Shu Huang
- Department of Gastroenterology, The People’s Hospital of Lianshui, Huaian 223400, Jiangsu Province, China
| | - Xiao Pan
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China
- Department of Gastroenterology, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, Sichuan Province, China
| | - Hui-Fang Xia
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China
- Department of Gastroenterology, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, Sichuan Province, China
| | - Xin-Yi Zeng
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China
- Department of Gastroenterology, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, Sichuan Province, China
| | - Wen-Sen Ren
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China
- Department of Gastroenterology, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, Sichuan Province, China
| | - Xian Zhou
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China
- Department of Gastroenterology, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, Sichuan Province, China
| | - Mu-Han Lv
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China
- Department of Gastroenterology, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, Sichuan Province, China
| | - Xiao-Wei Tang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China
- Department of Gastroenterology, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, Sichuan Province, China
| |
Collapse
|
|
31
|
Elshafie S, Trivedi‐Kapoor R, Ebell M. Safety and efficacy of sofosbuvir-based medication regimens with and without ribavirin in hepatitis C patients: A systematic review and meta-analysis. J Clin Pharm Ther 2022; 47:1149-1158. [PMID: 35678040 PMCID: PMC9545628 DOI: 10.1111/jcpt.13698] [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: 03/24/2022] [Revised: 04/03/2022] [Accepted: 04/25/2022] [Indexed: 12/09/2022]
Abstract
WHAT IS KNOWN AND OBJECTIVE Sofosbuvir (SOF) is a new and highly effective medication that dramatically improved hepatitis C virus (HCV) management. However, ribavirin (RBV) is still added to SOF-based medication regimens in several clinical scenarios, despite its well-known toxicities. The aim of our study is to systematically review and analyse the impact of adding RBV to SOF-based medication regimens on clinical outcomes among HCV patients. METHODS Included studies were randomized trials comparing the same SOF-based medication regimens with and without RBV in HCV patients and measuring serious adverse events (SAEs) and/or sustained virologic response at 12 weeks post-treatment (SVR-12). Two investigators independently searched PubMed and Cochrane Library through September 2021. The Cochrane Risk of Bias tool was used to assess trials quality. Clinical outcomes were analysed as risk ratios (RR) using a random effects model using R version 4.1.2. RESULTS AND DISCUSSION Our study included a total of 26 trials with 5058 HCV patients. Quality assessment showed moderate risk of bias for most trials. Upon adding RBV, there was no significant difference in SAEs (RR 1.07, 95% CI: 0.77-1.48, I2 = 10%), nor an impact on SVR-12 (RR 1.00, 95% CI: 0.98-1.01, I2 = 41%). There was no evidence of publication bias for either outcome. Subgroup analysis consistently showed lack of benefit among HCV subgroups. Additionally, NCT01826981 was identified as the main source of heterogeneity in the SVR-12 outcome. WHAT IS NEW AND CONCLUSION Our findings suggest nonsignificant differences in safety and efficacy between SOF-based medication regimens with and without RBV which should be considered in clinical practice.
Collapse
Affiliation(s)
- Shaimaa Elshafie
- Department of Clinical and Administrative Pharmacy, College of PharmacyUniversity of GeorgiaGeorgiaUSA
- Central Administration for Drug ControlEgyptian Drug AuthorityCairoEgypt
| | - Rupal Trivedi‐Kapoor
- Department of Clinical and Administrative Pharmacy, College of PharmacyUniversity of GeorgiaGeorgiaUSA
| | - Mark Ebell
- Department of Epidemiology, College of Public HealthUniversity of GeorgiaAthensGeorgiaUSA
| |
Collapse
|
|
32
|
Lo CC, Huang CF, Cheng PN, Tseng KC, Chen CY, Kuo HT, 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, Chen CT, Wang CC, Su WW, Hsieh TY, Lin CL, Tsai WL, Lee TH, Chen GY, Wang SJ, Chang CC, Mo LR, Yang SS, Wu WC, Huang CS, Hsiung CK, Kao CN, Tsai PC, Liu CH, Lee MH, Liu CJ, Dai CY, Chuang WL, Lin HC, Kao JH, Yu ML. Ledipasvir/sofosbuvir for HCV genotype 1, 2, 4-6 infection: Real-world evidence from a nationwide registry in Taiwan. J Formos Med Assoc 2022; 121:1567-1578. [PMID: 35123849 DOI: 10.1016/j.jfma.2022.01.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 12/08/2021] [Accepted: 01/11/2022] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND/PURPOSE The Taiwan Association for the Study of the Liver (TASL) HCV Registry (TACR) is a nationwide registry of chronic hepatitis C patients in Taiwan. This study evaluated antiviral effectiveness of ledipasvir (LDV)/sofosbuvir (SOF) in patients in the TACR. METHODS Patients enrolled in TACR from 2017-2020 treated with LDV/SOF were eligible. The primary outcome was the proportion of patients with sustained virologic response 12 weeks after end of treatment (SVR12). RESULTS 5644 LDV/SOF ± ribavirin-treated patients were included (mean age: 61.4 years; 54.4% female). Dominant viral genotypes were GT1 (50.8%) and GT2 (39.3%). 1529 (27.1%) patients had liver cirrhosis, including 201 (3.6%) with liver decompensation; 686 (12.2%) had chronic kidney disease. SVR12 was achieved in 98.6% of the overall population and in 98.2% and 98.7% of patients with and without cirrhosis, respectively. SVR12 rates in patients with compensated cirrhosis treated with LDV/SOF without RBV were >98%, regardless of prior treatment experience. SVR12 was 98.6%, 98.4%, 100%, 100%, and 98.7% among those with GT1, GT2, GT4, GT5, and GT6 infections, respectively. Although patient numbers were relatively small, SVR12 rates of 100% were reported in patients infected with HCV GT2, GT5, and GT6 with decompensated cirrhosis and 98% in patients with severely compromised renal function. LDV/SOF adherence ≤60% (P < 0.001) was the most important factor associated with treatment failure. Incidence of adverse events was 15.8%, with fatigue being the most common. CONCLUSION LDV/SOF is effective and well tolerated in routine clinical practice in Taiwan. Cure rates were high across patient populations.
Collapse
Affiliation(s)
- Ching-Chu Lo
- Division of Gastroenterology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan; Chung-Jen Junior College of Nursing, Health Sciences and Management, 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, Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, 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
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi; School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Taiwan
| | - Hsing-Tao Kuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, 710, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 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, School of Medicine, China Medical University, Taichung, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, 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, Taiwan
| | - Ming-Lun Yeh
- School of Medicine and Hepatitis Research Center, College of Medicine, 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, 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
- Chi Mei Medical Center, Liouying Division of Gastroenterology and Hepatology, Department of Internal Medicine, 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, 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, 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, Taiwan
| | - Jui-Ting Hu
- Liver Center, Cathay General Hospital, Taiwan
| | - Chih-Wen Lin
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 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
| | - Chia-Chi Wang
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Taiwan
| | - Wei-Wen Su
- Department of Gastroenterology and Hepatology, Changhua Christian Hospital, 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, Renai Branch, Taipei City Hospital, Taipei, Taiwan
| | - Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Taiwan
| | - Tzong-Hsi Lee
- Division of Gastroenterology and Hepatology, Far Eastern Memorial Hospital, Taiwan
| | | | - Szu-Jen Wang
- Division of Gastroenterology, Department of Internal Medicine, Yuan's General Hospital, Taiwan
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taiwan
| | - Lein-Ray Mo
- Division of Gastroenterology, Tainan Municipal Hospital, Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | | | | | | | - Chien-Neng Kao
- National Taiwan University Hospital Hsin-Chu Branch, 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, Taiwan
| | - Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taiwan
| | - Chun-Jen Liu
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, 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 and Cohort Research, Kaohsiung Medical University, Kaohsiung, 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 and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taiwan
| | - Jia-Horng Kao
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, 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, Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
| |
Collapse
|
|
33
|
Tsai WL, Cheng JS, Liu PF, Chang TH, Sun WC, Chen WC, Shu CW. Sofosbuvir induces gene expression for promoting cell proliferation and migration of hepatocellular carcinoma cells. Aging (Albany NY) 2022; 14:5710-5726. [PMID: 35833210 PMCID: PMC9365546 DOI: 10.18632/aging.204170] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Accepted: 05/13/2022] [Indexed: 11/29/2022]
Abstract
Direct-acting antivirals (DAAs) have achieved a sustained virological response (SVR) rate of 95–99% in treating HCV. Several studies suggested that treatment with sofosbuvir (SOF), one type of DAAs, may be associated with increased risk of developing HCC. The aim of this study is to investigate the potential mechanisms of SOF on the development of HCC. OR-6 (harboring full-length genotype 1b HCV) and Huh 7.5.1 cells were used to examine the effects of SOF on cell proliferation and migration of HCC cells. SOF-upregulated genes in OR-6 cells were inspected using next generation sequencing (NGS)and the clinical significance of these candidate genes was analyzed using The Cancer Genome Atlas (TCGA) database. We found that SOF increased cell proliferation and cell migration in OR-6 and Huh 7.5.1 cells. Several SOF-upregulated genes screened from NGS were confirmed by real-time PCR in OR-6 cells. Among these genes, PHOSPHO2, KLHL23, TRIM39, TSNAX-DISC1 and RPP21 expression were significantly elevated in the tumor tissues compared with the non-tumor tissues of HCC according to TCGA database. High expression of PHOSPHO2 and RPP21 was associated with poor overall survival of HCC patients. Moreover, knockdown of PHOSPHO2-KLHL23, TSNAX-DISC1, TRIM39 and RPP21 diminished cell proliferation and migration increased by SOF in OR-6 and Huh 7.5.1 cells. In conclusion, SOF-upregulated genes promoted HCC cell proliferation and migration, which might be associated with the development of HCC.
Collapse
Affiliation(s)
- Wei-Lun Tsai
- Division of General Internal Medicine, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,School of Nursing, Fooyin University, Kaohsiung, Taiwan
| | - Jin-Shiung Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Pei-Feng Liu
- Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Tsung-Hsien Chang
- Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan
| | - Wei-Chih Sun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Wen-Chi Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Chih-Wen Shu
- Institute of BioPharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan
| |
Collapse
|
|
34
|
Lee J, Ahn SB, Yim SY, An J, Jun DW, Ko MJ, Park DA, Yoo JJ. Efficacy and safety of direct-acting antiviral therapy for hepatitis C virus in elderly patients (≥65 years old): A systematic review and meta-analysis. J Viral Hepat 2022; 29:496-517. [PMID: 35357774 DOI: 10.1111/jvh.13679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 02/07/2022] [Accepted: 03/11/2022] [Indexed: 12/09/2022]
Abstract
Direct-acting agents (DAAs) have launched a new era of hepatitis C virus (HCV) treatment. As aged individuals comprise a large percentage of HCV-infected patients, the effectiveness and safety of DAAs in the elderly have come under scrutiny. This meta-analysis aimed to evaluate the efficacy and safety of DAAs in elderly patients. After a systematic search in PubMed (MEDLINE), Embase, OVID MEDLINE, the Cochrane Library and other databases, two investigators reviewed relevant abstracts and selected manuscripts for examination. The sustained virologic response (SVR) and adverse event (AE) rates were calculated with a random-effects model. Ninety studies evaluating SVR rates of elderly patients (≥65 years old) receiving DAAs were selected. DAAs in elderly patients exhibited a notable SVR rate of 96% (95% confidence interval [CI]: 95%-97%), accompanied by comparable rates in subgroup analyses. The comparison of SVR rates in elderly and non-elderly patients indicated no significant discrepancy (odds ratio [OR] 1.01, 95% CI: 1.00-1.01). The overall event rate of AEs was 45% (95% CI: 31%-60%), though AE rates varied by subgroups. Furthermore, AEs were comparatively more frequent (OR 1.15, 95% CI: 1.04-1.28) in the elderly than non-elderly, especially in subgroups such as SAE (OR 1.89, 95% CI: 1.52-2.36) and dose reduction in ribavirin (OR 1.90, 95% CI: 1.53-2.36). However, in the ribavirin (RBV)-free regimen, there was no significant difference in the incidence of AEs between the elderly and non-elderly groups. DAAs have high efficacy in elderly patients. Considering the possibility of AE, the RBV-free regimen should be given prior consideration for the treatment of elderly patients with HCV.
Collapse
Affiliation(s)
- Jieun Lee
- College of Medicine, Soonchunhyang University, Cheonan, Korea
| | - Sang Bong Ahn
- Nowon Eulji Medical Center, Department of Internal Medicine, Eulji University College of Medicine, Seoul, Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University Hospital, Seoul, Korea
| | - Jihyun An
- Gastroenterology and Hepatology, Hanyang University College of Medicine, Guri, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Min Jung Ko
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency (NECA), Seoul, Korea
| | - Dong Ah Park
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency (NECA), Seoul, Korea
| | - Jeong-Ju Yoo
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| |
Collapse
|
|
35
|
Vernuccio F, Cannella R, Cabibbo G, Greco S, Celsa C, Matteini F, Giuffrida P, Midiri M, Di Marco V, Cammà C, Brancatelli G. Role of LI-RADS Indeterminate Observations in the Risk of Hepatocellular Carcinoma after HCV Eradication with Direct-Acting Antivirals. Diagnostics (Basel) 2022; 12:diagnostics12051187. [PMID: 35626341 PMCID: PMC9140370 DOI: 10.3390/diagnostics12051187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/29/2022] [Accepted: 05/05/2022] [Indexed: 11/16/2022] Open
Abstract
Purpose: To assess whether HCC (LR-5) occurrence may be associated with the presence of Liver Imaging Reporting and Data System (LI-RADS) indeterminate observations in patients with hepatitis C virus infection treated with direct acting antiviral (DAA) therapy. Materials and methods: This retrospective study included patients with HCV-related cirrhosis who achieved sustained virologic response (SVR) after DAA therapy between 2015 and 2019 and submitted to CT/MRI follow-ups with a minimum interval time of six months before and after DAA. Two blinded readers reviewed CT/MRI to categorize observations according to LI-RADS version 2018. Differences in rate of LI-RADS 5 observations (i.e., LR-5) before and after SVR were assessed. Time to LR-5 occurrence and risk factors for HCC after DAAs were evaluated by using Kaplan-Meier method and Cox proportional hazard model, respectively. Results: Our final study population comprised 115 patients (median age 72 years) with a median CT/MRI follow-up of 47 months (IQR 26–77 months). Twenty-nine (25.2%) patients were diagnosed with LR-5 after DAA. The incidence of LR-5 after DAAs was 10.4% (12/115) at one year and 17.4% (20/115) at two years. LR-5 occurrence after DAA was significantly higher in patients with Child Pugh class B (log-rank p = 0.048) and with LR-3 or LR-4 observations (log-rank p = 0.024). At multivariate analysis, Child-Pugh class B (hazard ratio 2.62, p = 0.023) and presence of LR-3 or LR-4 observations (hazard ratio 2.40, p = 0.048) were independent risk factors for LR-5 occurrence after DAA therapy. Conclusions: The presence of LR-3 and LR-4 observations significantly increases HCC risk following the eradication of HCV infection.
Collapse
Affiliation(s)
- Federica Vernuccio
- Department of Radiology, University Hospital of Padova, Via Nicolò Giustiniani 2, 35128 Padova, Italy
- Section of Radiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University Hospital “Paolo Giaccone”, Via del Vespro 129, 90127 Palermo, Italy; (R.C.); (S.G.); (F.M.); (M.M.); (G.B.)
- Correspondence: ; Tel.: +39-388-6332212
| | - Roberto Cannella
- Section of Radiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University Hospital “Paolo Giaccone”, Via del Vespro 129, 90127 Palermo, Italy; (R.C.); (S.G.); (F.M.); (M.M.); (G.B.)
- Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy; (G.C.); (C.C.); (P.G.); (V.D.M.); (C.C.)
| | - Giuseppe Cabibbo
- Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy; (G.C.); (C.C.); (P.G.); (V.D.M.); (C.C.)
| | - Silvia Greco
- Section of Radiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University Hospital “Paolo Giaccone”, Via del Vespro 129, 90127 Palermo, Italy; (R.C.); (S.G.); (F.M.); (M.M.); (G.B.)
| | - Ciro Celsa
- Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy; (G.C.); (C.C.); (P.G.); (V.D.M.); (C.C.)
- Department of Surgical, Oncological and Oral Sciences (Di.Chir.On.S.), University of Palermo, 90127 Palermo, Italy
| | - Francesco Matteini
- Section of Radiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University Hospital “Paolo Giaccone”, Via del Vespro 129, 90127 Palermo, Italy; (R.C.); (S.G.); (F.M.); (M.M.); (G.B.)
| | - Paolo Giuffrida
- Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy; (G.C.); (C.C.); (P.G.); (V.D.M.); (C.C.)
| | - Massimo Midiri
- Section of Radiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University Hospital “Paolo Giaccone”, Via del Vespro 129, 90127 Palermo, Italy; (R.C.); (S.G.); (F.M.); (M.M.); (G.B.)
| | - Vito Di Marco
- Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy; (G.C.); (C.C.); (P.G.); (V.D.M.); (C.C.)
| | - Calogero Cammà
- Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy; (G.C.); (C.C.); (P.G.); (V.D.M.); (C.C.)
| | - Giuseppe Brancatelli
- Section of Radiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University Hospital “Paolo Giaccone”, Via del Vespro 129, 90127 Palermo, Italy; (R.C.); (S.G.); (F.M.); (M.M.); (G.B.)
| |
Collapse
|
|
36
|
Jindal A. Letter to the editor: Oral antivirals in treatment-naïve chronic hepatitis C infection. Hepatology 2022; 75:1339. [PMID: 34984728 DOI: 10.1002/hep.32311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 07/22/2021] [Accepted: 07/24/2021] [Indexed: 12/08/2022]
Affiliation(s)
- Ankur Jindal
- Department of HepatologyInstitute of Liver and Biliary SciencesNew DelhiIndia
| |
Collapse
|
|
37
|
Odenwald MA, Paul S. Viral hepatitis: Past, present, and future. World J Gastroenterol 2022; 28:1405-1429. [PMID: 35582678 PMCID: PMC9048475 DOI: 10.3748/wjg.v28.i14.1405] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Revised: 03/04/2022] [Accepted: 03/06/2022] [Indexed: 02/06/2023] Open
Abstract
Each hepatitis virus-Hepatitis A, B, C, D, E, and G-poses a distinct scenario to the patient and clinician alike. Since the discovery of each virus, extensive knowledge regarding epidemiology, virologic properties, and the natural clinical and immunologic history of acute and chronic infections has been generated. Basic discoveries about host immunologic responses to acute and chronic viral infections, combined with virologic data, has led to vaccines to prevent Hepatitis A, B, and E and highly efficacious antivirals for Hepatitis B and C. These therapeutic breakthroughs are transforming the fields of hepatology, transplant medicine in general, and public and global health. Most notably, there is even an ambitious global effort to eliminate chronic viral hepatitis within the next decade. While attainable, there are many barriers to this goal that are being actively investigated in basic and clinical labs on the local, national, and international scales. Herein, we discuss pertinent clinical information and recent organizational guidelines for each of the individual hepatitis viruses while also synthesizing this information with the latest research to focus on exciting future directions for each virus.
Collapse
Affiliation(s)
- Matthew August Odenwald
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, Center for Liver Diseases, University of Chicago, Chicago, IL 60637, United States
| | - Sonali Paul
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, Center for Liver Diseases, University of Chicago, Chicago, IL 60637, United States
| |
Collapse
|
|
38
|
Factors Associated with the Refusal of Direct-Acting Antiviral Agents for the Treatment of Hepatitis C in Taiwan. Medicina (B Aires) 2022; 58:medicina58040521. [PMID: 35454360 PMCID: PMC9031294 DOI: 10.3390/medicina58040521] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 03/29/2022] [Accepted: 04/01/2022] [Indexed: 12/12/2022] Open
Abstract
Background and Objectives: Direct-acting antiviral agents (DAA) are a safe and highly effective treatment for hepatitis C virus (HCV) infection. However, the uptake of DAA treatment remains a challenge. This study aims to examine the reasons for DAA refusal among HCV patients covered by the Taiwan National Health Insurance system. Materials and Methods: This retrospective observational study covered the period from January 2009 to December 2019 and was conducted at a single hepatitis treatment center in Taiwan. This study involved chart reviews and phone-based surveys to confirm treatment status and refusal causes. To confirm treatment status, subjects with HCV without treatment records were phone-contacted to confirm treatment status. Patients who did not receive treatment were invited back for treatment. If the patient refused, the reason for refusal was discussed. Results: A total of 3566 patients were confirmed with DAA treatment; 418 patients (179 patients who were lost to contact or refused the survey and 239 patients who completed the survey of DAA refusal) were included in the no-DAA-therapy group. Factors associated with receiving DAAs were hemoglobin levels, hepatitis B virus co-infection, and regular gastroenterology visits. Meanwhile, male sex, platelet levels, and primary care physician visits were associated with DAA refusal. The leading causes of treatment refusal were multiple comorbidities, low health literacy, restricted access to hospitals, nursing home residence, and old age. The rate of DAA refusal remains high (10%). Conclusions: The reasons for treatment refusal are multifactorial, and addressing them requires complex interventions.
Collapse
|
|
39
|
Loucks CM, Lin JJ, Trueman JN, Drögemöller BI, Wright GEB, Chang WC, Li KH, Yoshida EM, Ford JA, Lee SS, Crotty P, Kim RB, Al-Judaibi B, Schwarz UI, Ramji A, Farivar JF, Tam E, Walston LL, Ross CJD, Carleton BC. Patient-specific genetic factors predict treatment failure in sofosbuvir-treated patients with chronic hepatitis C. Liver Int 2022; 42:796-808. [PMID: 35107877 DOI: 10.1111/liv.15175] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 01/12/2022] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS According to pivotal clinical trials, cure rates for sofosbuvir-based antiviral therapy exceed 96%. Treatment failure is usually assumed to be because of virological resistance-associated substitutions or clinical risk factors, yet the role of patient-specific genetic factors has not been well explored. We determined if patient-specific genetic factors help predict patients likely to fail sofosbuvir treatment in real-world treatment situations. METHODS We recruited sofosbuvir-treated patients with chronic hepatitis C from five Canadian treatment sites, and performed a case-control pharmacogenomics study assessing both previously published and novel genetic polymorphisms. Specifically studied were variants predicted to impair CES1-dependent production of sofosbuvir's active metabolite, interferon-λ signalling variants expected to impact a patient's immune response to the virus and an HLA variant associated with increased spontaneous and treatment-induced viral clearance. RESULTS Three hundred and fifty-nine sofosbuvir-treated patients were available for analyses after exclusions, with 34 (9.5%) failing treatment. We identified CES1 variants as novel predictors for treatment failure in European patients (rs115629050 or rs4513095; odds ratio (OR): 5.43; 95% confidence interval (CI): 1.64-18.01; P = .0057), replicated associations with IFNL4 variants predicted to increase interferon-λ signalling (eg rs12979860; OR: 2.25; 95% CI: 1.25-4.06; P = .0071) and discovered a novel association with a coding variant predicted to enhance the activity of IFNL4's receptor (rs2834167 in IL10RB; OR: 1.81; 95% CI: 1.01-3.24; P = .047). CONCLUSIONS Ultimately, this work demonstrates that patient-specific genetic factors could be used as a tool to identify patients at higher risk of treatment failure and allow for these patients to receive effective therapy sooner.
Collapse
Affiliation(s)
- Catrina M Loucks
- BC Children's Hospital Research Institute, Vancouver, Canada.,Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.,Department of Anesthesiology, Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada
| | - Jennifer J Lin
- BC Children's Hospital Research Institute, Vancouver, Canada.,Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.,Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, Canada
| | - Jessica N Trueman
- BC Children's Hospital Research Institute, Vancouver, Canada.,Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada
| | - Britt I Drögemöller
- Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Galen E B Wright
- Department of Pharmacy and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Wan-Chun Chang
- BC Children's Hospital Research Institute, Vancouver, Canada.,Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada
| | - Kathy H Li
- BC Children's Hospital Research Institute, Vancouver, Canada.,Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada
| | - Eric M Yoshida
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, Canada
| | - Jo-Ann Ford
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, Canada
| | - Samuel S Lee
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, Canada
| | - Pam Crotty
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, Canada
| | - Richard B Kim
- Division of Clinical Pharmacology, Department of Medicine, Western University, London, Canada
| | - Bandar Al-Judaibi
- Division of Transplantation, University of Rochester, Rochester, New York, USA.,Department of Liver Transplantation and Hepatobiliary Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Ute I Schwarz
- Division of Clinical Pharmacology, Department of Medicine, Western University, London, Canada
| | - Alnoor Ramji
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, Canada
| | | | | | | | - Colin J D Ross
- BC Children's Hospital Research Institute, Vancouver, Canada.,Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.,Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada
| | - Bruce C Carleton
- BC Children's Hospital Research Institute, Vancouver, Canada.,Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.,Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.,Pharmaceutical Outcomes Program (POPi), British Columbia Children's Hospital, Vancouver, Canada
| |
Collapse
|
|
40
|
Pharmacist-led drug therapy management for Hepatitis C at a federally qualified healthcare center. J Am Pharm Assoc (2003) 2022; 62:1596-1605. [DOI: 10.1016/j.japh.2022.04.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 04/15/2022] [Accepted: 04/20/2022] [Indexed: 11/18/2022]
|
|
41
|
Inukai Y, Imai N, Yamamoto K, Ito T, Ishizu Y, Honda T, Okamoto S, Kanematsu T, Suzuki N, Matsushita T, Ishigami M, Fujishiro M. The influence of hepatitis C virus eradication on hepatocarcinogenesis in patients with hemophilia. Ann Hepatol 2022; 27:100545. [PMID: 34571264 DOI: 10.1016/j.aohep.2021.100545] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 05/21/2021] [Accepted: 05/24/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Hepatitis C virus (HCV) infections in patients with hemophilia lead to the development of hepatocellular carcinoma (HCC) at a relatively younger age than that in patients without hemophilia. Although recent progress in direct-acting-antivirals has facilitated a high rate of sustained virological response (SVR), the clinical influence of HCV eradication in hemophilia patients remains unclear. This study aimed to compare the clinical outcomes of SVR against HCV in patients with and without hemophilia. PATIENTS AND METHODS The study enrolled 699 patients who achieved SVR after HCV antiviral treatment. Patients were divided into two groups: 78 patients with hemophilia (H group) and 621 patients without hemophilia (NH group). We evaluated patient characteristics, clinical outcomes, and the cumulative incidence of HCC after SVR. RESULTS Compared with the NH group, patients in the H-group were significantly younger and had a lower hepatic fibrosis score. No difference was found in the incidence of liver-related disease or overall death between the two groups over a mean follow-up period of 7 years. Four patients in the H group and 36 patients in the NH group were diagnosed with HCC after SVR. Multivariate analysis showed that male sex, age, and cirrhosis were significant risk factors for HCC incidence. There was no significant difference in the cumulative incidence of HCC after propensity-score matching adjusting for the risk factors of HCC between the two groups. CONCLUSION Hemophilia is not a significant risk factor for hepatocarcinogenesis after SVR against HCV.
Collapse
Affiliation(s)
- Yosuke Inukai
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Norihiro Imai
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine.
| | - Kenta Yamamoto
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Yoji Ishizu
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Shuichi Okamoto
- Department of Hematology and Oncology, Nagoya University Graduate School of Medicine
| | | | - Nobuaki Suzuki
- Department of Transfusion Medicine, Nagoya University Hospital
| | - Tadashi Matsushita
- Department of Clinical Laboratory, Nagoya University Hospital; Department of Transfusion Medicine, Nagoya University Hospital
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| |
Collapse
|
|
42
|
Four Weeks Treatment with Glecaprevir/Pibrentasvir + Ribavirin-A Randomized Controlled Clinical Trial. Viruses 2022; 14:v14030614. [PMID: 35337021 PMCID: PMC8948928 DOI: 10.3390/v14030614] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 03/14/2022] [Indexed: 01/25/2023] Open
Abstract
Enhancing treatment uptake for hepatitis C to achieve the elimination goals set by the World Health Organization could be achieved by reducing the treatment duration. The aim of this study was to compare the sustained virological response at week 12 (SVR12) after four weeks of glecaprevir/pibrentasvir (GLE/PIB) + ribavirin compared to eight weeks of GLE/PIB and to estimate predictors for SVR12 with four weeks of treatment through a multicenter open label randomized controlled trial. Patients were randomized 2:1 (4 weeks:8 weeks) and stratified by genotype 3 and were treatment naïve of all genotypes and without significant liver fibrosis. A total of 27 patients were analyzed for predictors for SVR12, including 15 from the first pilot phase of the study. In the ‘modified intention to treat’ group, 100% (7/7) achieved cure after eight weeks and for patients treated for four weeks the SVR12 was 58.3% (7/12). However, patients with a baseline viral load <2 mill IU/mL had 93% SVR12. The study closed prematurely due to the low number of included patients due to the COVID-19 pandemic. Our results suggest that viral load should be taken into account when considering trials of short course treatment.
Collapse
|
|
43
|
Boyer S, Baudoin M, Nishimwe ML, Santos M, Lemoine M, Maradan G, Sylla B, Kouanfack C, Carrieri P, Mourad A, Rouveau N, Moh R, Seydi M, Attia A, Woode ME, Lacombe K. Cost-utility analysis of four WHO-recommended sofosbuvir-based regimens for the treatment of chronic hepatitis C in sub-Saharan Africa. BMC Health Serv Res 2022; 22:303. [PMID: 35248039 PMCID: PMC8897946 DOI: 10.1186/s12913-021-07289-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 11/12/2021] [Indexed: 11/25/2022] Open
Abstract
Background Although direct-acting antivirals (DAA) have become standard care for patients with chronic hepatitis C worldwide, there is no evidence for their value for money in sub-Saharan Africa. We assessed the cost-effectiveness of four sofosbuvir-based regimens recommended by the World Health Organization (WHO) in Cameroon, Côte d’Ivoire and Senegal. Methods Using modelling, we simulated chronic hepatitis C progression with and without treatment in hypothetical cohorts of patients infected with the country’s predominant genotypes (1, 2 and 4) and without other viral coinfections, history of liver complication or hepatocellular carcinoma. Using the status-quo ‘no DAA treatment’ as a comparator, we assessed four regimens: sofosbuvir-ribavirin, sofosbuvir-ledipasvir (both recommended in WHO 2016 guidelines and assessed in the TAC pilot trial conducted in Cameroon, Côte d’Ivoire and Senegal), sofosbuvir-daclatasvir and sofosbuvir-ledipasvir (two pangenotypic regimens recommended in WHO 2018 guidelines). DAA effectiveness, costs and utilities were mainly estimated using data from the TAC pilot trial. Secondary data from the literature was used to estimate disease progression probabilities with and without treatment. We considered two DAA pricing scenarios: S1) originator prices; S2) generic prices. Uncertainty was addressed using probabilistic and deterministic sensitivity analyses and cost-effectiveness acceptability curves. Results With slightly higher effectiveness and significantly lower costs, sofosbuvir/velpatasvir was the preferred DAA regimen in S1 with incremental cost-effectiveness ratios (ICERs) ranging from US$526 to US$632/QALY. At the cost-effectiveness threshold (CET) of 0.5 times the 2017 country’s per-capita gross domestic product (GDP), sofosbuvir/velpatasvir was only cost-effective in Senegal (probability > 95%). In S2 at generic prices, sofosbuvir/daclatasvir was the preferred regimen due to significantly lower costs. ICERs ranged from US$139 to US$216/QALY according to country i.e. a 95% probability of being cost-effective. Furthermore, this regimen was cost-effective (probability> 95%) for all CET higher than US$281/QALY, US$223/QALY and US$195/QALY in Cameroon, Côte d’Ivoire and Senegal, respectively, corresponding to 0.14 (Côte d’Ivoire and Senegal) and 0.2 (Cameroon) times the country’s per-capita GDP. Conclusions Generic sofosbuvir/daclatasvir is very cost-effective for treating chronic hepatitis C in sub-Saharan Africa. Large-scale use of generics and an increase in national and international funding for hepatitis C treatment must be priorities for the HCV elimination agenda. Supplementary Information The online version contains supplementary material available at 10.1186/s12913-021-07289-0.
Collapse
|
|
44
|
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.
Collapse
|
|
45
|
Effect of Silymarin as an Adjunct Therapy in Combination with Sofosbuvir and Ribavirin in Hepatitis C Patients: A Miniature Clinical Trial. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:9199190. [PMID: 35154575 PMCID: PMC8828344 DOI: 10.1155/2022/9199190] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 12/29/2021] [Indexed: 02/06/2023]
Abstract
Silymarin is proclaimed to be a blend of flavonolignans or phytochemicals. An era of new generation of direct-acting antivirals (DAAs) has commenced to have facet effect in swaying of the hepatitis C virus (HCV). Nonetheless, this therapy has serious side effects that jeopardize its efficacy. This study is aimed at probing the effects of ribavirin (RBV) and sofosbuvir (SOF) along with silymarin as an adjunct therapy on hematological parameters and markers of obscured oxidative stress. The effect of DAAs along with silymarin was also examined on variable sex hormone level and liver function markers such as alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and bilirubin. The study was followed to determine viral load and viral genotypes. A total of 30 patients were randomly divided into two equal groups comprising the control group (n = 15) and treatment group (n = 15). The control group was solely administered with DAAs (SOF and RBV; 400 mg/800 mg each/day). Conversely, the treatment group was dispensed with DAAs, but with adjunct therapy of silymarin (400 mg/day) along with DAAs (400/800 mg/day) over period of 8 weeks. Sampling of blood was performed at pre- and posttreatment levels for the evaluation of different propound parameters. Our data showed that silymarin adjunct therapy enhances the efficiency of DAAs. A decrease in menace level of liver markers such as ALT, ALP, AST, and bilirubin was observed (p > 0.05). The adjunct therapy concurrently also demonstrated an ameliorative effect on hematological indices and oxidative markers, for instance, SOD, TAS, GSH, GSSG, and MDA (p < 0.05), diminishing latent viral load. The silymarin administration was also found to revamp the fluster level of sex hormones. Our outcomes provide evidence that systematic administration of silymarin effectively remits deviant levels of hematological, serological, hormonal, and antioxidant markers. This demonstrates a possibly unique role of silymarin in mitigating hepatitis C.
Collapse
|
|
46
|
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.
Collapse
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.
| |
Collapse
|
|
47
|
Abstract
The development of direct-acting antivirals (DAA) has revolutionized the treatment of chronic hepatitis C, enabling cure of hepatitis C virus (HCV) infection in more than 95% of cases. There are essentially no contraindications, so almost any patient can now be successfully treated. The result is the prevention or amelioration of cirrhosis, hepatocellular carcinoma (HCC), and extrahepatic manifestations. Consequently, the 2020 Nobel Prize in Medicine and Physiology was awarded for the discovery of HCV. Due to the high efficacy of therapy, even global HCV elimination is conceivable even without a vaccine. Here, we would like to venture a SWOT analysis of current HCV therapies aimed at HCV elimination.
Collapse
Affiliation(s)
- Markus Cornberg
- Department of Gastroenterology, Hepatology, and Endocrinology, 9177Hannover Medical School Hannover, Hannover, Germany.,Centre for Individualised Infection Medicine (CiiM), a joint venture of Helmholtz Centre for Infection Research and Hannover Medical School, Hannover, Germany.,German Center for Infection Research (DZIF), Partner-Site Hannover-Braunschweig, Hannover, Germany
| | | |
Collapse
|
|
48
|
OUP accepted manuscript. J Antimicrob Chemother 2022; 77:1396-1403. [DOI: 10.1093/jac/dkac051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 01/12/2022] [Indexed: 11/12/2022] Open
|
|
49
|
Yoeli D, Choudhury RA, Moore HB, Sauaia A, Simpson MA, Pomfret EA, Nydam TL. Are Hepatitis C Positive Female Liver Transplant Recipients Still at Increased Risk for Graft Failure? Reexamining the Disparity in the Modern Era of Direct-acting Antiviral Agents. Transplantation 2022; 106:129-137. [PMID: 33577252 DOI: 10.1097/tp.0000000000003683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND This study aimed to compare the outcomes of hepatitis C virus (HCV) positive (+) female liver transplant recipients to HCV negative (-) female and HCV+ male recipients before and after the direct-acting-antiviral (DAA) era. METHODS The United Network for Organ Sharing liver transplant database was retrospectively reviewed from 2002 to 2017. The DAA era was defined as ≥2014. RESULTS In the pre-DAA era, HCV+ female recipients had greater risk for graft failure compared with HCV+ male (hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.01-1.11; P = 0.03) and HCV- female (HR, 1.51; 95% CI, 1.43-1.60; P < 0.001) recipients. In the post-DAA era, HCV+ female recipients had lower risk for graft failure compared with HCV+ male recipients (HR, 0.82; 95% CI, 0.70-0.97; P = 0.02) and equivalent outcomes to HCV- female recipients. HCV+ female recipients with graft failure had increased likelihood of graft failure due to disease recurrence compared with HCV+ male recipients in the pre-DAA era (odds ratio, 1.23; 95% CI, 1.08-1.39; P = 0.001) but not in the post-DAA era. CONCLUSIONS Although historically HCV+ female recipients were at disproportionately increased risk for graft failure and disease recurrence, this disparity has been eliminated in the DAA era.
Collapse
Affiliation(s)
- Dor Yoeli
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO
| | - Rashikh A Choudhury
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO
| | - Hunter B Moore
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO
| | - Angela Sauaia
- Colorado School of Public Health, University of Colorado Denver, Aurora, CO
| | - Mary Ann Simpson
- Department of Transplantation, Lahey Hospital and Medical Center, Burlington, MA
| | - Elizabeth A Pomfret
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO
| | - Trevor L Nydam
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO
| |
Collapse
|
|
50
|
Martel-Laferrière V, Brissette S, Wartelle-Bladou C, Juteau LC, Popa M, Goyer MÈ, Bruneau J. Impact of an Accelerated Pretreatment Evaluation on Linkage-to-Care for Hepatitis C-infected Persons Who Inject Drugs. Subst Abuse 2022; 16:11782218221119068. [PMID: 35990750 PMCID: PMC9382068 DOI: 10.1177/11782218221119068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 07/25/2022] [Indexed: 11/15/2022]
Abstract
Background: Historically, hepatitis C virus (HCV) pretreatment evaluation has required multiple visits, frequently resulting in loss to follow-up and a delayed initiation of treatment. New technologies can accelerate this process. We investigated the feasibility of a single-day evaluation program and its impact on evaluation completion, treatment eligibility awareness, and treatment initiation among people who inject drugs (PWIDs). Methods: HCV-infected PWID who were unaware if they were eligible for treatment were recruited in a prospective evaluation of an accelerated model of care between 2017 and 2019 and compared to a historical cohort. The patients underwent a medical evaluation, rapid HCV viral load testing, and transient elastography during a single visit, at the end of which they were informed whether they were eligible for treatment. A historical cohort of patients fulfilling the same inclusion criteria and evaluated with the usual standard of care spanning several visits who were examined at the addiction medicine clinic from 2014 to 2016 served as the comparison group. Results: The accelerated and historical cohorts included 99 and 76 patients, respectively. The cohorts did not differ significantly by age and gender, but more patients in the historical cohort were undergoing opioid agonist therapy, while more patients in the accelerated cohort injected drugs in the last month. An accelerated evaluation resulted in a higher rate of evaluation completion (100% vs 67.1%; P < .001). Among those eligible for treatment, the proportion of those initiating treatment was similar between the groups (51/64 (79.7%) vs. 26/37 (70.3%); P = .28). The delay in the initiation of treatment was shorter in the accelerated cohort than in the historical cohort (69 (IQR: 49-106) days vs. 219 (IQR: 141-416) days; P < .001). Conclusions: Accelerated evaluation enhanced the awareness of eligibility and reduced the time to initiation among eligible patients. Trial Registration: This study is registered on www.clinicaltrials.gov (NCT02755402).
Collapse
Affiliation(s)
- Valérie Martel-Laferrière
- Université de Montréal, Montreal, QC, Canada
- Centre hospitalier de l’Université de Montréal, Montreal, QC, Canada
- Centre de recherche du Centre hospitalier de l’Université de Montréal, Montreal, QC, Canada
| | - Suzanne Brissette
- Université de Montréal, Montreal, QC, Canada
- Centre hospitalier de l’Université de Montréal, Montreal, QC, Canada
- Centre de recherche du Centre hospitalier de l’Université de Montréal, Montreal, QC, Canada
| | - Claire Wartelle-Bladou
- Université de Montréal, Montreal, QC, Canada
- Centre hospitalier de l’Université de Montréal, Montreal, QC, Canada
- Centre de recherche du Centre hospitalier de l’Université de Montréal, Montreal, QC, Canada
| | - Louis-Christophe Juteau
- Université de Montréal, Montreal, QC, Canada
- Centre hospitalier de l’Université de Montréal, Montreal, QC, Canada
- Centre de recherche du Centre hospitalier de l’Université de Montréal, Montreal, QC, Canada
| | - Maria Popa
- Université de Montréal, Montreal, QC, Canada
| | - Marie-Ève Goyer
- Université de Montréal, Montreal, QC, Canada
- CIUSSS du Centre-Sud de Montréal, Montreal, QC, Canada
| | - Julie Bruneau
- Université de Montréal, Montreal, QC, Canada
- Centre hospitalier de l’Université de Montréal, Montreal, QC, Canada
- Centre de recherche du Centre hospitalier de l’Université de Montréal, Montreal, QC, Canada
| |
Collapse
|