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Panahi I, Selvey LA, Puljević C, Kvassay A, Grimstrup D, Smirnov A. 'You've Just Got to Keep Pestering': Barriers and Enablers of Attaining Continuity of Hepatitis C Care for People Transitioning Between Prison and Community Health Services in South-East Queensland, Australia. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2025; 22:238. [PMID: 40003464 PMCID: PMC11855011 DOI: 10.3390/ijerph22020238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Revised: 02/03/2025] [Accepted: 02/03/2025] [Indexed: 02/27/2025]
Abstract
Highly effective direct-acting antiviral (DAA) therapies for hepatitis C (HCV) have been available in Australian prisons since 2016. To address treatment interruption following release from prisons, the Queensland Injector's Health Network (QuIHN) launched a Prison Transition Service (PTS) in south-east Queensland, Australia. Presently, the factors associated with continuity of post-release HCV care are poorly understood. The objective of this qualitative study was to explore the barriers and facilitators to HCV treatment among people recently released from prisons among PTS clients and stakeholders. Qualitative interviews were conducted with 27 participants, namely, 13 clients and 14 stakeholders (health and community support workers) of the PTS. We conducted thematic analysis using the framework of person-, provider-, and system-level barriers and facilitators. Person-level barriers included competing priorities post-release, while facilitators included self-improvement after treatment completion, preventing transmission to family, and social support. Provider-level treatment barriers included enacted stigma, limited prison health service capacity, and post-release health system challenges. Systemic barriers included stigma relating to HCV, injecting drug use, incarceration, and limited availability of harm reduction services. Policy changes and investment are required to expand HCV treatment in south-east Queensland prisons to facilitate patient navigation into community care. In terms of reducing stigma among health staff and the general community towards people with HCV, a history of incarceration and/or who inject drugs is crucial for improving treatment rates. Strategies such as peer-led or nurse-practitioner-led models of care may help improve treatment completion. Continuity of HCV treatment post-release from prisons is essential for Australia to meet the WHO's 2030 HCV elimination target.
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Affiliation(s)
- Idin Panahi
- School of Public Health, The University of Queensland, Herston, QLD 4006, Australia (A.S.)
| | - Linda A. Selvey
- School of Public Health, The University of Queensland, Herston, QLD 4006, Australia (A.S.)
| | - Cheneal Puljević
- School of Public Health, The University of Queensland, Herston, QLD 4006, Australia (A.S.)
| | - Amanda Kvassay
- Queensland Injectors Health Network, Bowen Hills, QLD 4006, Australia
| | - Dorrit Grimstrup
- Queensland Injectors Health Network, Bowen Hills, QLD 4006, Australia
| | - Andrew Smirnov
- School of Public Health, The University of Queensland, Herston, QLD 4006, Australia (A.S.)
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Jose-Abrego A, Laguna-Meraz S, Roman S, Mariscal-Martinez IM, Panduro A. Hepatitis C Virus Resistance-Associated Substitutions in Mexico. Viruses 2025; 17:169. [PMID: 40006924 PMCID: PMC11860613 DOI: 10.3390/v17020169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Revised: 01/10/2025] [Accepted: 01/13/2025] [Indexed: 02/27/2025] Open
Abstract
Hepatitis C virus (HCV) is susceptible to resistance-associated substitutions (RASs) in the NS3, NS5A, and NS5B nonstructural genes, key targets of the direct-acting antivirals (DAAs). This study aimed to assess the prevalence and distribution of RASs across different HCV subtypes in Mexico. A Genbank dataset of 566 HCV sequences was analyzed. Most sequences were from Mexico City (49.1%, 278/566) and Jalisco (39.4%, 223/566). The NS5B region was the most sequenced (59.7%, 338/566). The most frequent HCV subtypes were 1a (44.0%, 249/566), 1b (28.6%, 162/566), 2b (9.5%, 54/566), and 3a (6.2%, 35/566). Subtypes 1a (57.4%, 128/223) and 3a (12.6%, 28/223) were significantly higher in Jalisco than in Mexico City (34.2%, 95/278 and 2.5%, 7/278), whereas subtype 1b was higher in Mexico City (34.5%, 96/278 vs. 14.8%, 33/223). Subtype 1a increased from 2019 to 2024, representing 49.4% (123/249) of all reported cases. RASs were detected in NS3 (6.7%, 1/15), NS5A (2.9%, 3/102), and NS5B (0.3%, 1/349), with the most frequent mutations being Q80K, Y93H, and S282T, respectively, and detected in subtypes 1b (n = 3), 1a (n = 1), and 2a (n = 1). In conclusion, Mexico's HCV sequencing-based surveillance is limited. Subtype 1a predominated, but frequencies varied across states. The prevalence of RASs varied by gene from 0.3% to 6.7%. Establishing regional sequencing centers for NS3, NS5A, and NS5B is crucial to monitoring Mexico's DAA-resistant mutations and HCV subtype genetic diversity.
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Affiliation(s)
- Alexis Jose-Abrego
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, Fray Antonio Alcalde, Guadalajara 44280, Mexico; (A.J.-A.); (S.L.-M.); (S.R.); (I.M.M.-M.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Mexico
| | - Saul Laguna-Meraz
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, Fray Antonio Alcalde, Guadalajara 44280, Mexico; (A.J.-A.); (S.L.-M.); (S.R.); (I.M.M.-M.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Mexico
| | - Sonia Roman
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, Fray Antonio Alcalde, Guadalajara 44280, Mexico; (A.J.-A.); (S.L.-M.); (S.R.); (I.M.M.-M.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Mexico
| | - Irene M. Mariscal-Martinez
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, Fray Antonio Alcalde, Guadalajara 44280, Mexico; (A.J.-A.); (S.L.-M.); (S.R.); (I.M.M.-M.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Mexico
- Doctoral Program Molecular Biology in Medicine, Health Sciences Center, University of Guadalajara, Guadalajara 44340, Mexico
| | - Arturo Panduro
- Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, Fray Antonio Alcalde, Guadalajara 44280, Mexico; (A.J.-A.); (S.L.-M.); (S.R.); (I.M.M.-M.)
- Health Sciences Center, University of Guadalajara, Guadalajara 44340, Mexico
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Yi S, Truong D, Conway B. Long-term outcome in people who use drugs successfully treated for hepatitis C infection with glecaprevir/pibrentasvir. J Virus Erad 2024; 10:100569. [PMID: 39807127 PMCID: PMC11728950 DOI: 10.1016/j.jve.2024.100569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 11/28/2024] [Accepted: 11/28/2024] [Indexed: 01/16/2025] Open
Abstract
Background Several clinical trials, including the recently published the GRAND PLAN study from Vancouver Infectious Diseases Center (VIDC), have demonstrated the efficacy of hepatitis C (HCV) therapy among active drug users, including those facing significant addiction-related and social challenges. In the GRAND PLAN, we documented sustained virological response post-treatment Week12 (SVR12) in 108/117 (92.3 %) individuals (108/111 (mITT) or 97.3 % of those reaching the SVR12 timepoint) receiving an 8-week course of glecaprevir/pibrentasvir (G/P), with almost all using fentanyl and over half being unstably housed. Data on the maintenance of this favorable outcome in the long-term in such a population with a significant risk of reinfection is limited. We hypothesized that the offer of ongoing multidisciplinary care (including addiction care) after SVR12 was achieved would reduce the likelihood of loss to follow up, HCV reinfection or death and consolidate the gains achieved by initial engagement in care to diagnose and treat HCV infection. Methods The inception cohort for this analysis was the 108 individuals achieving a cure of HCV infection within the GRAND PLAN study. All were offered the opportunity to continue to receive care at the VIDC. This is a multidisciplinary model of care to address medical, mental health, social and addiction-related concerns on an ongoing basis. This included, if necessary, opiate agonist and safer supply therapy, usually provided by the pharmacy adjacent to our inner-city campus. Among those choosing to be retained in care, the endpoint of this analysis was loss to follow up, mortality and HCV reinfection and their correlates. Reinfection was ascertained by repeat HCV RNA testing every 6 months, more frequently if clinically indicated. Results Of the 108 individuals making up the inception cohort for this analysis, all chose to remain in care at the VIDC. We note a median age of 47 (22-75) years, 28 % female, 21.3 % identifying as indigenous, the majority with mild fibrosis (90.8 % F0-F2), slightly more than half with unstable housing. It is of note that we recorded a 20 % decrease in fentanyl users among those who were cured compared to the baseline evaluation of the overall study cohort (73.5 % vs 94.9 %, p < 0.000001). Among the cured individuals, 104 (96.3 %) remained alive, while 4 individuals died of opioid overdoses. Out of the 104 , 99 (95.2 %) remained HCV-free, while 5 (4.8 %) were re-infected. All five have recently initiated repeat HCV therapy at VIDC, 2 of whom are already documented to be cured. Conclusion Among a population of vulnerable inner-city residents cured of HCV infection within a multidisciplinary program of care at the VIDC, all individuals accepted the offer to remain in long-term follow up, with a statistically significant reduction in fentanyl use over time. In the setting of an ongoing opioid crisis where 3 deaths/day are recorded in the neighborhood where the study population resides, we documented 4 deaths. Reinfections occurred at a very modest rate, with maintenance in care allowing prompt re-treatment, with a cure already being documented in 2/5 cases, with the other 3 individuals remaining on HCV therapy at the VIDC.
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Affiliation(s)
- Shana Yi
- Vancouver Infectious Diseases Center, Vancouver, British Columbia, Canada
| | - David Truong
- Vancouver Infectious Diseases Center, Vancouver, British Columbia, Canada
| | - Brian Conway
- Vancouver Infectious Diseases Center, Vancouver, British Columbia, Canada
- Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada
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Yi S, Truong D, Conway B. A comparison of sofosbuvir/velpatasvir and glecaprevir/pibrentasvir for the treatment of hepatitis C infection among people who inject drugs. J Virus Erad 2024; 10:100388. [PMID: 39319041 PMCID: PMC11420441 DOI: 10.1016/j.jve.2024.100388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 08/14/2024] [Accepted: 08/29/2024] [Indexed: 09/26/2024] Open
Abstract
Background To eliminate hepatitis C (HCV) infection as a public health concern by 2030, there is a need to develop comprehensive programs among key populations such as people who use drugs (PWUD). Two highly effective regimens are available for initial therapy: glecaprevir/pibrentasvir (G/P) given as 3 tablets/day for 8 weeks and sofosbuvir/velpatasvir (S/V) given as 1 tablet/day for 12 weeks. Data evaluating the safety and efficacy comparing one regimen over another in a population of PWUD is limited. Methods Patients were identified through outreach events. Viremic patients were offered HCV treatment within a multidisciplinary program. This retrospective comparison analysis focuses on the first 120 sequential individuals who chose either treatment and in whom a definitive outcome of treatment was available between March 1, 2019 and February 29, 2024. The primary outcomes of the analysis were cure of HCV infection and its corelates, as well as safety of the individual regimens. Results We successfully identified 120 within each of the G/P and S/V treatment groups. Of those on G/P, we note 28.3 % female, 20.9 % Indigenous, 70.8 % using fentanyl, and 51.3 % with unstable housing. Of those on S/V, we note 25.8 % female, 20.8 % Indigenous, and 75 % using fentanyl and 56.7 % with unstable housing. Overall, 118 and 115 patients completed therapy on G/P and S/V, respectively. A total of 118 and 115 completed therapy on G/P and S/V, with virologic relapse documented in 3 and 2 participants on G/P and S/V, respectively. The ITT/mITT cure rates for G/P and S/V were 95.0 %/97.4 % and 94.2 %/98.3 %, respectively. There were 5 drug overdose deaths among those who initiated treatment, one on G/P and 4 on S/V. Conclusion: We have evaluated two highly effective regimens in a group of inner-city PWUD, with comparable success rates well in excess of 90 %. Our data supports the offer of both options for the treatment of PWUD with HCV infection.
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Affiliation(s)
- Shana Yi
- Vancouver Infectious Diseases Centre, Vancouver, British Columbia, Canada
| | - David Truong
- Vancouver Infectious Diseases Centre, Vancouver, British Columbia, Canada
| | - Brian Conway
- Vancouver Infectious Diseases Centre, Vancouver, British Columbia, Canada
- Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada
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Toyodome A, Mawatari S, Eguchi H, Takeda M, Kumagai K, Taniyama O, Ijuin S, Sakae H, Tabu K, Oda K, Ikeda M, Ido A. Analysis of the susceptibility of refractory hepatitis C virus resistant to nonstructural 5A inhibitors. Sci Rep 2024; 14:16363. [PMID: 39013947 PMCID: PMC11252252 DOI: 10.1038/s41598-024-67169-5] [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: 01/15/2024] [Accepted: 07/09/2024] [Indexed: 07/18/2024] Open
Abstract
Resistance-associated substitutions (RASs) of hepatitis C virus (HCV) affect the efficacy of direct-acting antivirals (DAAs). In this study, we aimed to clarify the susceptibility of the coexistence of nonstructural (NS) 5A Q24K/L28M/R30Q (or R30E)/A92K RASs, which were observed in patients with DAAs re-treatment failure and to consider new therapeutic agents. We used a subgenomic replicon system in which HCV genotype 1B strain 1B-4 was electroporated into OR6c cells derived from HuH-7 cells (Wild-type [WT]). We converted WT genes to NS5A Q24K/L28M/R30Q/A92K or Q24/L28K/R30E/A92K. Compared with the WT, the Q24K/L28M/R30Q/A92K RASs was 36,000-fold resistant to daclatasvir, 440,000-fold resistant to ledipasvir, 6300-fold resistant to velpatasvir, 3100-fold resistant to elbasvir, and 1.8-fold resistant to pibrentasvir. Compared with the WT, the Q24K/L28M/R30E/A92K RASs was 640,000-fold resistant to daclatasvir and ledipasvir, 150,000-fold resistant to velpatasvir, 44,000-fold resistant to elbasvir, and 1500-fold resistant to pibrentasvir. The Q24K/L28M/R30E/A92K RASs was 816.3 times more resistant to pibrentasvir than the Q24K/L28M/R30Q/A92K RASs. Furthermore, a combination of pibrentasvir and sofosbuvir showed therapeutic efficacy against these RASs. Combination regimens may eradicate HCV with NS5A Q24K/L28M/R30E/A92K RASs.
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Affiliation(s)
- Ai Toyodome
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan
| | - Seiichi Mawatari
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan.
| | - Hiromi Eguchi
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan
| | - Midori Takeda
- Division of Biological Information Technology, Joint Research Center for Human Retrovirus Infection, Kagoshima University, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan
| | - Kotaro Kumagai
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan
| | - Ohki Taniyama
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan
| | - Sho Ijuin
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan
| | - Haruka Sakae
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan
| | - Kazuaki Tabu
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan
| | - Kohei Oda
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan
| | - Masanori Ikeda
- Division of Biological Information Technology, Joint Research Center for Human Retrovirus Infection, Kagoshima University, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan
| | - Akio Ido
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8‑35‑1 Sakuragaoka, Kagoshima, 890‑8544, Japan
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Morita A, Tamaki N, Kobashi H, Mori N, Tsuji K, Takaki S, Hasebe C, Akahane T, Ochi H, Mashiba T, Urawa N, Fujii H, Mitsuda A, Kondo M, Ogawa C, Uchida Y, Narita R, Marusawa H, Kubotsu Y, Matsushita T, Shigeno M, Yoshida H, Tanaka K, Okamoto E, Kasai T, Ishii T, Okada K, Kurosaki M, Izumi N. Effect of treatment periods on efficacy of glecaprevir and pibrentasvir in chronic hepatitis C: A nationwide, prospective, multicenter study. JGH Open 2024; 8:e13068. [PMID: 38681824 PMCID: PMC11046085 DOI: 10.1002/jgh3.13068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 03/26/2024] [Accepted: 04/03/2024] [Indexed: 05/01/2024]
Abstract
Background and aim In patients with chronic hepatitis C, 8 weeks of glecaprevir and pibrentasvir (GLE/PIB) treatment for chronic hepatitis (non-cirrhosis) and 12 weeks for cirrhosis have been approved in Japan. However, whether 8 weeks of treatment for cirrhosis may reduce treatment efficacy has not been adequately investigated. Methods This prospective, nationwide, multicenter cohort study enrolled 1275 patients with chronic hepatitis C who received GLE/PIB therapy. The effect of liver fibrosis and treatment periods on the efficiency of GLE/PIB therapy was investigated. The primary endpoint was the sustained virological response (SVR) rate in patients with chronic hepatitis (non-cirrhosis) and cirrhosis. The association between treatment periods and liver fibrosis on the SVR after 12 weeks of treatment rate was investigated. Results The SVR rates in patients with chronic hepatitis with 8 weeks of treatment, chronic hepatitis with 12 weeks of treatment, cirrhosis with 8 weeks of treatment, and cirrhosis with 12 weeks of treatment were 98.9% (800/809), 100% (87/87), 100% (166/166), and 99.1% (211/213), respectively, and were was not different among these groups (P = 0.4). Conclusion GLE/PIB therapy for chronic hepatitis C had high efficacy regardless of liver fibrosis status and treatment periods. Periods of GLE/PIB therapy could be chosen with available modalities, and high SVR rates could be achieved regardless of the decision.
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Affiliation(s)
- Atsuhiro Morita
- Department of GastroenterologyJapanese Red Cross Kyoto Daini HospitalKyotoJapan
| | - Nobuharu Tamaki
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Haruhiko Kobashi
- Department of GastroenterologyJapanese Red Cross Okayama HospitalOkayamaJapan
| | - Nami Mori
- Department of GastroenterologyHiroshima Red Cross Hospital & Atomic‐bomb Survivors HospitalHiroshimaJapan
| | - Keiji Tsuji
- Department of GastroenterologyHiroshima Red Cross Hospital & Atomic‐bomb Survivors HospitalHiroshimaJapan
| | - Shintaro Takaki
- Department of GastroenterologyHiroshima Red Cross Hospital & Atomic‐bomb Survivors HospitalHiroshimaJapan
| | - Chitomi Hasebe
- Department of GastroenterologyJapanese Red Cross Asahikawa HospitalAsahikawaJapan
| | - Takehiro Akahane
- Department of GastroenterologyIshinomaki Red Cross HospitalIshinomakiJapan
| | - Hironori Ochi
- Center for Liver‐Biliary‐Pancreatic DiseaseMatsuyama Red Cross HospitalMatsuyamaJapan
| | - Toshie Mashiba
- Center for Liver‐Biliary‐Pancreatic DiseaseMatsuyama Red Cross HospitalMatsuyamaJapan
| | - Naohito Urawa
- Department of Gastroenterology and HepatologyIse Red Cross HospitalIseJapan
| | - Hideki Fujii
- Department of GastroenterologyJapanese Red Cross Kyoto Daiichi HospitalKyotoJapan
| | - Akeri Mitsuda
- Department of GastroenterologyTottori Red Cross HospitalTottoriJapan
| | - Masahiko Kondo
- Department of GastroenterologyOtsu Red Cross HospitalOtsuJapan
| | - Chikara Ogawa
- Department of Gastroenterology and HepatologyTakamatsu Red Cross HospitalTakamatsuJapan
| | - Yasushi Uchida
- Department of GastroenterologyMatsue Red Cross HospitalMatsueJapan
| | - Ryoichi Narita
- Department of GastroenterologyOita Red Cross HospitalOitaJapan
| | - Hiroyuki Marusawa
- Department of Gastroenterology and HepatologyOsaka Red Cross HospitalOsakaJapan
| | | | | | - Masaya Shigeno
- Department of GastroenterologyJapanese Red Cross Nagasaki Genbaku HospitalNagasakiJapan
| | - Hideo Yoshida
- Department of GastroenterologyJapanese Red Cross Medical CenterTokyoJapan
| | - Katsuaki Tanaka
- Department of GastroenterologyHatano Red Cross HospitalHatanoJapan
| | - Eisuke Okamoto
- Department of GastroenterologyMasuda Red Cross HospitalMasudaJapan
| | - Toyotaka Kasai
- Department of GastroenterologyFukaya Red Cross HospitalSaitamaJapan
| | - Toru Ishii
- Department of GastroenterologyJapanese Red Cross Akita HospitalAkitaJapan
| | - Kazuhiko Okada
- Department of GastroenterologyToyama Red Cross HospitalToyamaJapan
| | - Masayuki Kurosaki
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Namiki Izumi
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
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Shin HD, Song IH, Lee SH, Kim HS, Lee TH, Eun HS, Kim SH, Lee BS, Chae HB, Kim SH, Song MJ, Ko SY, Kim SB. Comparison of Glecaprevir/Pibrentasvir and Sofosbuvir/Ledipasvir in Patients with Hepatitis C Virus Genotype 1 and 2 in South Korea. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2024; 83:111-118. [PMID: 38522854 DOI: 10.4166/kjg.2023.141] [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: 11/23/2023] [Revised: 01/15/2024] [Accepted: 02/04/2024] [Indexed: 03/26/2024]
Abstract
Background/Aims This study compared the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/ledipasvir (SOF/LDV) in real-life clinical practice. Methods The data from genotype 1 or 2 chronic hepatitis C patients treated with GLE/PIB or sofosbuvir + ribavirin or SOF/LDV in South Korea were collected retrospectively. The analysis included the treatment completion rate, sustained virologic response at 12 weeks (SVR12) test rate, treatment effectiveness, and adverse events. Results Seven hundred and eighty-two patients with genotype 1 or 2 chronic hepatitis C who were treated with GLE/PIB (n=575) or SOF/LDV (n=207) were included in this retrospective study. The baseline demographic and clinical characteristics revealed significant statistical differences in age, genotype, ascites, liver cirrhosis, and hepatocellular carcinoma between the GLE/PIB and SOF/LDV groups. Twenty-two patients did not complete the treatment protocol. The treatment completion rate was high for both regimens without statistical significance (97.7% vs. 95.7%, p=0.08). The overall SVR12 of intention-to-treat analysis was 81.2% vs. 80.7% without statistical significance (p=0.87). The overall SVR12 of per protocol analysis was 98.7% vs. 100% without statistical significance (p=0.14). Six patients treated with GLE/PIB experienced treatment failure. They were all male, genotype 2, and showed a negative hepatitis C virus RNA level at the end of treatment. Two patients treated with GLE/PIB stopped medication because of fever and abdominal discomfort. Conclusions Both regimens had similar treatment completion rates, effectiveness, and safety profiles. Therefore, the SOF/LDV regimen can also be considered a viable DAA for the treatment of patients with genotype 1 or 2 chronic hepatitis C.
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Affiliation(s)
- Hyun Deok Shin
- Department of Gastroenterology, Dankook University College of Medicine, Cheonan, Korea
| | - Il Han Song
- Department of Gastroenterology, Dankook University College of Medicine, Cheonan, Korea
| | - Sae Hwan Lee
- Department of Gastroenterology, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Hong Soo Kim
- Department of Gastroenterology, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Tae Hee Lee
- Department of Gastroenterology, Konyang University College of Medicine, Daejeon, Korea
| | - Hyuk Soo Eun
- Department of Gastroenterology, Chungnam University College of Medicine, Daejeon, Korea
| | - Seok Hyun Kim
- Department of Gastroenterology, Chungnam University College of Medicine, Daejeon, Korea
| | - Byung Seok Lee
- Department of Gastroenterology, Chungnam University College of Medicine, Daejeon, Korea
| | - Hee Bok Chae
- Department of Gastroenterology, Chungbuk University College of Medicine, Cheongju, Korea
| | - Seok Hwan Kim
- Department of Gastroenterology, College of Medicine, The Catholic University of Korea, Daejeon, Korea
| | - Myung Joon Song
- Department of Gastroenterology, College of Medicine, The Catholic University of Korea, Daejeon, Korea
| | - Soon Yeong Ko
- Department of Gastroenterology, Konkuk University College of Medicine, Chungju, Korea
| | - Suk Bae Kim
- Department of Gastroenterology, Dankook University College of Medicine, Cheonan, Korea
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Conway B, Yi S, Yung R, Sharma S. GRAND PLAN: Safety and Efficacy of Glecaprevir/Pibrentasvir for the Treatment of Hepatitis C Virus Infection Among People Initially Disengaged From Health Care Who Use Drugs-A Systematic Multidisciplinary Approach. Open Forum Infect Dis 2024; 11:ofad638. [PMID: 38444819 PMCID: PMC10914366 DOI: 10.1093/ofid/ofad638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Indexed: 03/07/2024] Open
Abstract
Background GRAND PLAN is a prospective, open-label, phase 4 study. Based at a single center and with a single arm, GRAND PLAN evaluated the safety and efficacy of an 8-week course of glecaprevir/pibrentasvir (G/P) among active drug users with hepatitis C virus (HCV) infection in a population enriched for factors that may reduce treatment uptake and success, such as disengagement from health care and unstable housing. Methods Participants were ≥19 years old and actively using drugs and were confirmed viremic, noncirrhotic, and HCV treatment naive. All participants provided informed consent before any study procedures. They received G/P for 8 weeks within a multidisciplinary model of care, with daily, weekly, or monthly dispensing of medications to optimize adherence. Results We identified 117 eligible patients with a median age of 46 years (range, 22-75): 27% were female, 21.4% were Indigenous, 48.7% were unstably housed, and 95.7% were active drug users (94.9% fentanyl). One patient did not start treatment, and 4 underwent <1 week of treatment, leaving 112 completed treatments with 94.6% picking up medications weekly. HCV RNA was undetectable at the end of treatment in all 112 patients. One died of unknown causes shortly after treatment. A cure was demonstrated in 108 of 111 (97.3%) cases at the SVR12 time point (sustained virologic response at ≥12 weeks); the other 3 experienced virologic relapse. Considering the entire cohort, the intent-to-treat success rate was 92.3% (108/117). HCV reinfection was documented at SVR24 in 5 cases, 2 of which were successfully retreated. Conclusions GRAND PLAN demonstrates that administration of an 8-week course of G/P to inner-city residents with HCV infection leads to a cure >95%. With a short course of treatment, G/P is an attractive option for this population in helping us achieve the World Health Organization's HCV objectives by 2030.
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Affiliation(s)
- Brian Conway
- Vancouver Infectious Diseases Center, Vancouver, British Columbia, Canada
- Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada
| | - Shana Yi
- Vancouver Infectious Diseases Center, Vancouver, British Columbia, Canada
| | - Rossitta Yung
- Vancouver Infectious Diseases Center, Vancouver, British Columbia, Canada
| | - Shawn Sharma
- Vancouver Infectious Diseases Center, Vancouver, British Columbia, Canada
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9
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Zingg SCW, Lemon K. Donor Viral Hepatitis and Liver Transplantation. Surg Clin North Am 2024; 104:67-77. [PMID: 37953041 DOI: 10.1016/j.suc.2023.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2023]
Abstract
Despite increasing numbers of organ transplants completed each year, there continues to be an organ shortage in liver transplantation. This has led to the utilization of previously discarded or "marginal" allografts, such as those from donors with hepatitis C virus (HCV) or hepatitis B virus (HBV). The advent of direct acting antivirals and nucleos(t)ide analogs has allowed these allografts to be safely transplanted regardless of the recipients' hepatitis status with comparable graft and patient survival. Recent advances have even allowed usage of actively viremic donors with similar graft and patient outcomes. This article presents an overview of the use of HCV positive and HBV positive allografts.
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Affiliation(s)
- Sara-Catherine Whitney Zingg
- Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267, USA. https://twitter.com/transplant_u
| | - Kristina Lemon
- Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267, USA; Division of Transplantation, University of Cincinnati School of Mediicne, 231 Albert Sabin Way, ML 0558, Cincinnati, OH 45267, USA.
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10
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Kotani K, Kawada N. Recent Advances in the Pathogenesis and Clinical Evaluation of Portal Hypertension in Chronic Liver Disease. Gut Liver 2024; 18:27-39. [PMID: 37842727 PMCID: PMC10791512 DOI: 10.5009/gnl230072] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 06/16/2023] [Accepted: 06/25/2023] [Indexed: 10/17/2023] Open
Abstract
In chronic liver disease, hepatic stellate cell activation and degeneration of liver sinusoidal endothelial cells lead to structural changes, which are secondary to fibrosis and the presence of regenerative nodules in the sinusoids, and to functional changes, which are related to vasoconstriction. The combination of such changes increases intrahepatic vascular resistance and causes portal hypertension. The subsequent increase in splanchnic and systemic hyperdynamic circulation further increases the portal blood flow, thereby exacerbating portal hypertension. In clinical practice, the hepatic venous pressure gradient is the gold-standard measure of portal hypertension; a value of ≥10 mm Hg is defined as clinically significant portal hypertension, which is severe and is associated with the risk of liver-related events. Hepatic venous pressure gradient measurement is somewhat invasive, so evidence on the utility of risk stratification by elastography and serum biomarkers is needed. The various stages of cirrhosis are associated with different outcomes. In viral hepatitis-related cirrhosis, viral suppression or elimination by nucleos(t)ide analog or direct-acting antivirals results in recompensation of liver function and portal pressure. However, careful follow-up should be continued, because some cases have residual clinically significant portal hypertension even after achieving sustained virologic response. In this study, we reviewed the current and future prospects for portal hypertension.
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Affiliation(s)
- Kohei Kotani
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Norifumi Kawada
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
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11
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Alghamdi AS, Alghamdi H, Alserehi HA, Babatin MA, Alswat KA, Alghamdi M, AlQutub A, Abaalkhail F, Altraif I, Alfaleh FZ, Sanai FM. SASLT guidelines: Update in treatment of hepatitis C virus infection, 2024. Saudi J Gastroenterol 2024; 30:S1-S42. [PMID: 38167232 PMCID: PMC10856511 DOI: 10.4103/sjg.sjg_333_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 11/27/2023] [Accepted: 12/03/2023] [Indexed: 01/05/2024] Open
Abstract
ABSTRACT Hepatitis C virus (HCV) infection has been a major global health concern, with a significant impact on public health. In recent years, there have been remarkable advancements in our understanding of HCV and the development of novel therapeutic agents. The Saudi Society for the Study of Liver Disease and Transplantation formed a working group to develop HCV practice guidelines in Saudi Arabia. The methodology used to create these guidelines involved a comprehensive review of available evidence, local data, and major international practice guidelines regarding HCV management. This updated guideline encompasses critical aspects of HCV care, including screening and diagnosis, assessing the severity of liver disease, and treatment strategies. The aim of this updated guideline is to assist healthcare providers in the management of HCV in Saudi Arabia. It summarizes the latest local studies on HCV epidemiology, significant changes in virus prevalence, and the importance of universal screening, particularly among high-risk populations. Moreover, it discusses the promising potential for HCV elimination as a public health threat by 2030, driven by effective treatment and comprehensive prevention strategies. This guideline also highlights evolving recommendations for advancing disease management, including the treatment of HCV patients with decompensated cirrhosis, treatment of those who have previously failed treatment with the newer medications, management in the context of liver transplantation and hepatocellular carcinoma, and treatment for special populations.
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Affiliation(s)
- Abdullah S. Alghamdi
- Department of Medicine, Gastroenterology Unit, King Fahad Hospital, Jeddah, Saudi Arabia
| | - Hamdan Alghamdi
- Hepatology Section, Hepatobiliary Sciences and Organs Transplant Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Haleema A. Alserehi
- General Directorate of Communicable Diseases, Ministry of Health, Riyadh, Saudi Arabia
| | - Mohammed A. Babatin
- Department of Medicine, Gastroenterology Unit, King Fahad Hospital, Jeddah, Saudi Arabia
| | - Khalid A. Alswat
- Liver Disease Research Center, and Riyadh, Saudi Arabia
- College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed Alghamdi
- Department of Medicine, Division of Gastroenterology, King Fahd Military Complex, Dhahran, Saudi Arabia
| | - Adel AlQutub
- Department of Gastroenterology and Hepatology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Faisal Abaalkhail
- Department of Medicine, Section of Gastroenterology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- College of Medicine, Al Faisal University, Riyadh, Saudi Arabia
| | - Ibrahim Altraif
- Hepatology Section, Hepatobiliary Sciences and Organs Transplant Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | | | - Faisal M. Sanai
- Liver Disease Research Center, and Riyadh, Saudi Arabia
- Gastroenterology Section, Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia
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12
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Coyle CR, Gicquelais RE, Genberg BL, Astemborski J, Falade-Nwulia O, Kirk GD, Thomas DL, Mehta SH. Temporal trends in HCV treatment uptake and success among people who inject drugs in Baltimore, MD since the introduction of direct acting antivirals. Drug Alcohol Depend 2023; 253:111007. [PMID: 38456165 PMCID: PMC10917145 DOI: 10.1016/j.drugalcdep.2023.111007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/09/2024]
Abstract
Background Although hepatitis C virus (HCV) can be cured by direct acting antivirals (DAA), uptake is not well characterized for people who inject drugs (PWID). Methods Among 1,130 participants of a community-based cohort of PWID with chronic HCV, we longitudinally characterized HCV treatment uptake and cure early (2014-2016) and later (2017-2020). Results Cumulative HCV treatment uptake increased from 4% in 2014 to 68% in 2020 and the percent with HCV viremia declined from nearly 100% to 33%. Predictors of treatment uptake varied across periods. Age (incidence rate ratio [IRR] per 5-year increase: 1.28; 95% confidence interval [CI]: 1.15, 1.42), educational attainment (IRR for ≥ high school diploma: 1.31; 95% CI: 1.04, 1.66), HIV coinfection with suppressed viral load (IRR vs. HIV negative: 2.08; 95% CI: 1.63, 2.66) and alcohol dependence (IRR vs. no alcohol use: 0.63; 95% CI: 0.43, 0.91) were associated with treatment uptake in the early period, but not later. HIV coinfection with a detectable viral load (IRR vs. HIV negative: 0.46; 95% CI: 0.23, 0.95) and daily injecting (IRR: 0.46 vs. no injection; 95% CI: 0.27, 0.79) were significantly associated with lower treatment uptake later. Homelessness was associated with significantly reduced likelihood of viral clearance in the late DAA era (IRR: 0.51; 95% CI: 0.30, 0.88). Conclusion Treatment uptake improved substantially in this cohort of PWID in the first five years of DAA availability with commensurate declines in viremia. Additional efforts are needed to treat those actively injecting and unstably housed in order to realize elimination goals.
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Affiliation(s)
- Catelyn R. Coyle
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, United States of America
- Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, United States of America
- Center for Observational and Real-World Evidence (CORE), Merck & Co, Inc, 351 N Sumneytown Pike, North Wales, PA 19454, United States of America
| | - Rachel E. Gicquelais
- School of Nursing, University of Wisconsin-Madison, 701 Highland Ave, Madison, WI 53705, United States of America
| | - Becky L. Genberg
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, United States of America
| | - Jacquie Astemborski
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, United States of America
| | - Oluwaseun Falade-Nwulia
- Division of Infectious Disease, Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, United States of America
| | - Gregory D. Kirk
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, United States of America
- Division of Infectious Disease, Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, United States of America
| | - David L. Thomas
- Division of Infectious Disease, Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, United States of America
| | - Shruti H. Mehta
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, United States of America
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13
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Kalluri HV, Oberoi RK, Chen Q, Jiang Q, Asatryan A, Alami NN, Yu C, Liu W. Pharmacokinetics, Tolerability, and Safety of Glecaprevir/Pibrentasvir Co-formulated Bilayer Tablet Following Repeated Administration in Healthy Chinese Adults. Clin Pharmacol Drug Dev 2023; 12:945-955. [PMID: 37661787 DOI: 10.1002/cpdd.1325] [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: 10/11/2021] [Accepted: 08/15/2023] [Indexed: 09/05/2023]
Abstract
Glecaprevir (GLE)/pibrentasvir (PIB) is an all-oral, interferon- and ribavirin-free, pan-genotypic fixed-dose combination regimen approved for the treatment of all major genotypes of hepatitis C virus (HCV) infection in many countries worldwide. To support clinical development in China, an open-label, single-center phase 1 study was conducted to evaluate the pharmacokinetics, safety, and tolerability of GLE/PIB in healthy Chinese adults in Mainland China. Eighteen participants received 3 tablets of coformulated GLE/PIB 100/40 mg once daily (QD) for 7 days. Following GLE/PIB 300 mg/120 mg administration, GLE and PIB reached maximum concentration in 4-5 hours with a terminal elimination half-life of 5.9 and 25 hours, respectively. Both GLE and PIB reached steady state by day 5, with no-to-minimal accumulation (≤17% higher). GLE/PIB exposures in healthy Chinese participants were similar to historical observations across phase 1 studies in healthy Western participants. GLE/PIB was safe and well-tolerated, with most adverse events being mild. These pharmacokinetics and safety data, together with existing global efficacy and safety data in healthy and HCV-infected Western participants, support the use of GLE/PIB 300 mg/120 mg QD in adult Chinese patients with chronic HCV infection.
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Affiliation(s)
- Hari V Kalluri
- Clinical Pharmacology, AbbVie Inc, North Chicago, IL, USA
| | | | - Qian Chen
- Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, China
| | - Qi Jiang
- Data and Statistical Sciences, AbbVie Inc, North Chicago, IL, USA
| | | | - Negar N Alami
- Infectious Diseases, AbbVie Inc, North Chicago, IL, USA
| | - Chen Yu
- Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, China
| | - Wei Liu
- Clinical Pharmacology, AbbVie Inc, North Chicago, IL, USA
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14
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Yadav Y, Singh K, Sharma S, Mishra VK, Sagar R. Recent Efforts in Identification of Privileged Scaffolds as Antiviral Agents. Chem Biodivers 2023; 20:e202300921. [PMID: 37589569 DOI: 10.1002/cbdv.202300921] [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: 06/23/2023] [Revised: 08/08/2023] [Accepted: 08/17/2023] [Indexed: 08/18/2023]
Abstract
Viral infections are the most important health concern nowadays to mankind, which is unexpectedly increasing the health complications and fatality rate worldwide. The recent viral infection outbreak developed a pressing need for small molecules that can be quickly deployed for the control/treatment of re-emerging or new emerging viral infections. Numerous viruses, including the human immunodeficiency virus (HIV), hepatitis, influenza, SARS-CoV-1, SARS-CoV-2, and others, are still challenging due to emerging resistance to known drugs. Therefore, there is always a need to search for new antiviral small molecules that can combat viral infection with new modes of action. This review highlighted recent progress in developing new antiviral molecules based on natural product-inspired scaffolds. Herein, the structure-activity relationship of the FDA-approved drugs along with the molecular docking studies of selected compounds have been discussed against several target proteins. The findings of new small molecules as neuraminidase inhibitors, other than known drug scaffolds, Anti-HIV and SARS-CoV are incorporated in this review paper.
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Affiliation(s)
- Yogesh Yadav
- Glycochemistry Laboratory, School of Physical Sciences, Jawaharlal Nehru University, New Delhi, 110067, India
| | - Kavita Singh
- Glycochemistry Laboratory, School of Physical Sciences, Jawaharlal Nehru University, New Delhi, 110067, India
| | - Sunil Sharma
- Glycochemistry Laboratory, School of Physical Sciences, Jawaharlal Nehru University, New Delhi, 110067, India
| | - Vinay Kumar Mishra
- Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi, 221005, India
| | - Ram Sagar
- Glycochemistry Laboratory, School of Physical Sciences, Jawaharlal Nehru University, New Delhi, 110067, India
- Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi, 221005, India
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15
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Martinello M, Solomon SS, Terrault NA, Dore GJ. Hepatitis C. Lancet 2023; 402:1085-1096. [PMID: 37741678 DOI: 10.1016/s0140-6736(23)01320-x] [Citation(s) in RCA: 69] [Impact Index Per Article: 34.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 05/30/2023] [Accepted: 06/22/2023] [Indexed: 09/25/2023]
Abstract
Hepatitis C virus (HCV) is a hepatotropic RNA virus that can cause acute and chronic hepatitis, with progressive liver damage resulting in cirrhosis, decompensated liver disease, and hepatocellular carcinoma. In 2016, WHO called for the elimination of HCV infection as a public health threat by 2030. Despite some progress, an estimated 57 million people were living with HCV infection in 2020, and 300 000 HCV-related deaths occur per year. The development of direct-acting antiviral therapy has revolutionised clinical care and generated impetus for elimination, but simplified and broadened HCV screening, enhanced linkage to care, and higher coverage of treatment and primary prevention strategies are urgently required.
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Affiliation(s)
- Marianne Martinello
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW Sydney, Sydney, NSW, Australia; Department of Infectious Diseases, Prince of Wales Hospital, Sydney, NSW, Australia.
| | - Sunil S Solomon
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Norah A Terrault
- Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, CA, USA
| | - Gregory J Dore
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW Sydney, Sydney, NSW, Australia; Department of Infectious Diseases, St Vincent's Hospital, Sydney, NSW, Australia
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16
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Yoshida Y, Atsukawa M, Kondo C, Kitamura M, Shioda-Koyano K, Kawano T, Ono H, Hayama K, Okubo T, Arai T, Itokawa N, Iwakiri K. A novel formula used for predicting hepatocellular carcinoma after the achievement of sustained virologic response by direct-acting antivirals in patients with chronic hepatitis C. PLoS One 2023; 18:e0292019. [PMID: 37733802 PMCID: PMC10513247 DOI: 10.1371/journal.pone.0292019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 09/08/2023] [Indexed: 09/23/2023] Open
Abstract
Although eliminating HCV can prevent hepatocellular carcinoma (HCC), some patients develop HCC even after obtaining sustained virologic response (SVR). Previously, we developed a new formula to predict advanced liver fibrosis. This study aimed to clarify the usefulness of this formula for predicting HCC after achieving SVR. Among 351 consecutive patients who had been treated with direct-acting antivirals, 299 were included in this study. New formula scores were used as a marker for predicting liver fibrosis and as a predictive model for HCC incidence. The participants were 172 men and 127 women with a median age of 68 years. The median new formula score was -1.291. The cumulative HCC incidence rates were 4.3%, 9.7%, and 12.5% at 1, 3, and 5 years, respectively. The cumulative incidence of HCC was significantly higher in patients with a history of HCC than in those without treatment history of HCC (P = 2.52×10-26). Multivariate analysis revealed that male (HR = 6.584, 95% CI = 1.291-33.573, P = 0.023) and new formula score (HR = 1.741, 95% CI = 1.041-2.911, P = 0.035) were independent factors associated with the development of HCC in patients without a treatment history of HCC. The optimal cutoff value for predicting the development of HCC was -0.214. The cumulative incidence rates of HCC in patients with new formula scores ≥-0.214 were 5.4%, 15.3%, and 15.3% at 1, 3, and 5 years, respectively, whereas the incidence rates of HCC in patients with new formula scores <-0.214 were 0.0%, 0.6%, and 4.8%, respectively (P = 2.12×10-4). In conclusion, this study demonstrated the usefulness of new formula scores as a predictor of HCC after achieving SVR, especially in patients without past treatment history of treatment for HCC.
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Affiliation(s)
- Yuji Yoshida
- Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Masanori Atsukawa
- Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Chisa Kondo
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Michika Kitamura
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Kaori Shioda-Koyano
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Tadamichi Kawano
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Hiroki Ono
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Korenobu Hayama
- Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Tomomi Okubo
- Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Taeang Arai
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Norio Itokawa
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Katsuhiko Iwakiri
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
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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: 16] [Impact Index Per Article: 8.0] [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.
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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
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18
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Fib-4 index predicts prognosis after achievement of sustained virologic response following direct-acting antiviral treatment in patients with hepatitis C virus infection. Eur J Gastroenterol Hepatol 2023; 35:219-226. [PMID: 36574313 DOI: 10.1097/meg.0000000000002479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
OBJECTIVES Toinvestigate liver carcinogenesis and other causes of death by collecting clinical data, including the Fib-4 index, from patients with successfully eradicated hepatitis C virus (HCV) by direct-acting antivirals (DAA) treatment. METHODS Patients ( n = 690), who achieved a sustained virologic response (SVR) between 2014 and 2021, were identified and followed up for approximately 6.8 years; 71 incident hepatocellular carcinoma (HCC) cases were identified. The Fib-4 index was calculated at DAA-treatment initiation and HCV eradication, and its relationship with carcinogenesis and prognosis was analyzed. RESULTS The Fib-4 index was initially calculated and divided into three groups: Fib-4<1.45, 1.45 ≤ Fib-4<3.25, and 3.25 ≤ Fib-4 to develop HCC over time. On analysis, no carcinogenic cases were observed at Fib-4<1.45. In patients with a Fib-4 index ≥3.25, the initial HCC carcinogenic rate was higher than that in patients with Fib-4=1.45-3.25, and a significant difference was obtained between the two groups [ P = 0.0057 (<1.45 vs. >3.25); P = 0.0004 (<1.45-3.25 vs. >3.25)]. Regarding all 18 death and Fib-4 at treatment initiation, a significant difference was observed after stratification into two groups [Fib-4 < 3.25 and 3.25 ≤ Fib-4; P = 0.0136 (<3.25 vs. ≥3.25)]. Significant differences were obtained in another analysis of 13 deaths, not due to HCC. CONCLUSIONS The high Fib-4 index calculated at baseline and SVR12 significantly correlated not only with liver carcinogenesis but also with all mortality rates, including those due to causes other than liver cancer. Our findings suggest that improving liver fibrosis by eradicating HCV improves prognosis related to all etiologies.
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Curtis MR, Chappell C. Evidence for Implementation: HIV/HCV Coinfection and Pregnancy. Curr HIV/AIDS Rep 2023; 20:1-8. [PMID: 36652107 PMCID: PMC9846668 DOI: 10.1007/s11904-022-00643-9] [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] [Accepted: 10/14/2022] [Indexed: 01/19/2023]
Abstract
PURPOSE OF REVIEW In the context of the opioid epidemic, hepatitis C virus (HCV) infection prevalence is increasing among women of reproductive age. Pregnant people with HIV/HCV coinfection may be at increased risk of adverse pregnancy and neonatal outcomes, although research in this key population is lacking. RECENT FINDINGS Treatment with directly acting antivirals (DAAs) has transformed the clinical care for most patients with HCV. However, pregnant people were excluded from trials of these medications. A recent phase I study has shown promise with excellent safety profile for ledipasvir-sofosbuvir; demonstrating no episodes of perinatal transmission, 100% sustained virologic response, and no safety concerns. Pregnancy represents a time of maximal interaction with the healthcare system and therefore an ideal window of opportunity to cure HCV. Current observational data regarding pregnant people who are co-infected with HCV and HIV suggest poor outcomes such as increased risk of preterm birth; however, there are no prospective and well-controlled studies to fully understand the impact of HIV/HCV coinfection on pregnancy. Phase 1 studies suggest that DAAs are well-tolerated and effective during pregnancy. Only through large, prospective clinical trials will we be able to understand the interaction of HCV and HIV during pregnancy and to evaluate safety and efficacy of DAAs in this key population.
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Affiliation(s)
- Megan Rose Curtis
- Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA.
- Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.
- Boston Medical Center, Boston, MA, USA.
- Harvard Medical School, Boston, MA, USA.
| | - Catherine Chappell
- Department of Obstetrics, Gynecology, and Reproductive sciences, University of Pittsburgh, PA, Pittsburgh, USA
- Magee-Women's Research Institute, Pittsburgh, PA, USA
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20
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Rodia R, Meloni PE, Mascia C, Balestrieri C, Ruggiero V, Serra G, Conti M, Loi M, Pes F, Onali S, Perra A, Littera R, Velluzzi F, Mariotti S, Chessa L, Boi F. Direct-acting antivirals used in HCV-related liver disease do not affect thyroid function and autoimmunity. J Endocrinol Invest 2023; 46:359-366. [PMID: 36048357 PMCID: PMC9859881 DOI: 10.1007/s40618-022-01909-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 08/19/2022] [Indexed: 01/25/2023]
Abstract
PURPOSE It is well known that interferon-α (IFN-α), used for long time as the main therapy for HCV-related disease, induces thyroid alterations, but the impact of the new direct-acting antivirals (DAAs) on thyroid is not established. Aim of this prospective study was to evaluate if DAAs therapy may induce thyroid alterations. METHODS A total of 113 HCV patients, subdivided at the time of the enrollment in naïve group (n = 64) and in IFN-α group (n = 49) previously treated with pegylated interferon-α and ribavirin, were evaluated for thyroid function and autoimmunity before and after 20-32 weeks of DAAs. RESULTS Before starting DAAs, a total of 8/113 (7.1%) patients showed Hashimoto's thyroiditis (HT) all belonging to IFN-α group (8/49, 16.3%), while no HT cases were found in the naïve group. Overall, 7/113 (6.2%) patients were hypothyroid: 3/64 (4.7%) belonging to naïve group and 4/49 (8.2%) to IFN-α group. Furthermore, a total of 8/113 patients (7.1%) showed subclinical hyperthyroidism: 2/64 (3.1%) were from naïve group and 6/49 (12.2%) from IFN-α group. Interestingly, after DAAs therapy, no new cases of HT, hypothyroidism and hyperthyroidism was found in all series, while 6/11 (54.5%) patients with non-autoimmune subclinical thyroid dysfunction became euthyroid. Finally, the only association between viral genotypes and thyroid alterations was genotype 1 and hypothyroidism. CONCLUSIONS This study supports evidence that DAAs have a limited or missing influence on thyroid in patients with HCV-related diseases. Moreover, it provides preliminary evidence that subclinical non-autoimmune thyroid dysfunction may improve after HCV infection resolution obtained by DAAs.
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Affiliation(s)
- R Rodia
- Endocrinology Unit, Department of Medical Sciences and Public Health, University of Cagliari, Azienda Ospedaliero-Universitaria di Cagliari, SS 554, Bivio per Sestu, 09042, Monserrato, Cagliari, Italy
| | - P E Meloni
- Endocrinology Unit, Department of Medical Sciences and Public Health, University of Cagliari, Azienda Ospedaliero-Universitaria di Cagliari, SS 554, Bivio per Sestu, 09042, Monserrato, Cagliari, Italy
| | - C Mascia
- Endocrinology Unit, Department of Medical Sciences and Public Health, University of Cagliari, Azienda Ospedaliero-Universitaria di Cagliari, SS 554, Bivio per Sestu, 09042, Monserrato, Cagliari, Italy
| | - C Balestrieri
- Centre of Liver Diseases, Department of Medical Sciences and Public Health, University of Cagliari, Azienda Ospedaliero-Universitaria di Cagliari, SS 554, Bivio per Sestu, 09042, Monserrato, Cagliari, Italy
| | - V Ruggiero
- Endocrinology Unit, Department of Medical Sciences and Public Health, University of Cagliari, Azienda Ospedaliero-Universitaria di Cagliari, SS 554, Bivio per Sestu, 09042, Monserrato, Cagliari, Italy
| | - G Serra
- Centre of Liver Diseases, Department of Medical Sciences and Public Health, University of Cagliari, Azienda Ospedaliero-Universitaria di Cagliari, SS 554, Bivio per Sestu, 09042, Monserrato, Cagliari, Italy
| | - M Conti
- Centre of Liver Diseases, Department of Medical Sciences and Public Health, University of Cagliari, Azienda Ospedaliero-Universitaria di Cagliari, SS 554, Bivio per Sestu, 09042, Monserrato, Cagliari, Italy
| | - M Loi
- Centre of Liver Diseases, Department of Medical Sciences and Public Health, University of Cagliari, Azienda Ospedaliero-Universitaria di Cagliari, SS 554, Bivio per Sestu, 09042, Monserrato, Cagliari, Italy
| | - F Pes
- Centre of Liver Diseases, Department of Medical Sciences and Public Health, University of Cagliari, Azienda Ospedaliero-Universitaria di Cagliari, SS 554, Bivio per Sestu, 09042, Monserrato, Cagliari, Italy
| | - S Onali
- Centre of Liver Diseases, Department of Medical Sciences and Public Health, University of Cagliari, Azienda Ospedaliero-Universitaria di Cagliari, SS 554, Bivio per Sestu, 09042, Monserrato, Cagliari, Italy
| | - A Perra
- Unit of Oncology and Molecular Pathology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy
| | - R Littera
- Complex Structure of Medical Genetics, R. Binaghi Hospital, ASSL Cagliari, ATS Sardegna, Cagliari, Italy
| | - F Velluzzi
- Endocrinology Unit, Department of Medical Sciences and Public Health, University of Cagliari, Azienda Ospedaliero-Universitaria di Cagliari, SS 554, Bivio per Sestu, 09042, Monserrato, Cagliari, Italy
| | - S Mariotti
- Endocrinology Unit, Department of Medical Sciences and Public Health, University of Cagliari, Azienda Ospedaliero-Universitaria di Cagliari, SS 554, Bivio per Sestu, 09042, Monserrato, Cagliari, Italy
| | - L Chessa
- Centre of Liver Diseases, Department of Medical Sciences and Public Health, University of Cagliari, Azienda Ospedaliero-Universitaria di Cagliari, SS 554, Bivio per Sestu, 09042, Monserrato, Cagliari, Italy
| | - F Boi
- Endocrinology Unit, Department of Medical Sciences and Public Health, University of Cagliari, Azienda Ospedaliero-Universitaria di Cagliari, SS 554, Bivio per Sestu, 09042, Monserrato, Cagliari, Italy.
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21
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Efficacy and safety of glecaprevir/pibrentasvir treatment in Koreans with chronic hepatitis C: A retrospective study. Arab J Gastroenterol 2023:S1687-1979(23)00006-0. [PMID: 36725375 DOI: 10.1016/j.ajg.2023.01.006] [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: 03/31/2021] [Revised: 11/12/2022] [Accepted: 01/08/2023] [Indexed: 02/03/2023]
Abstract
BACKGROUND AND STUDY AIMS The introduction of direct-acting antiviral (DAA) drugs has dramatically improved chronic hepatitis C (CHC) treatment. The pangenotype DAA therapy glecaprevir/pibrentasvir (G/P) was recently recommended for treating CHC in Korea. Unfortunately, given its recent introduction, little real-world data from a Korean population exists. We examined the effectiveness and safety of G/P treatment in Koreans with CHC. PATIENTS AND METHODS We analyzed CHC patients at Samsung Changwon Hospital from June 2018 to December 2020. Sustained virologic response at 12 weeks posttreatment (SVR 12) was evaluated after treatment, and the associated factors were analyzed. Furthermore, the degree of liver fibrosis before and after treatment was compared to determine whether liver fibrosis improved. RESULTS In total, 102 patients were enrolled; 35.3 % had compensated liver cirrhosis (LC), and 11.8 % had received previous treatment. Of the 102 patients, 99 (97.1 %) reached SVR 12. Of the 81 patients who completed 8 weeks of G/P treatment, 80 (98.8 %) reached SVR 12, while 19 of the 21 (90.5 %) patients in the 12- or 16-week group reached SVR 12, with no significant difference between the two groups (P = 0.107). As a secondary endpoint, liver fibrosis before and after treatment was also compared. The Fibrosis-4 index (FIB-4) (3.3 vs 2.8, P = 0.010), aspartate transaminase (AST)-platelet ratio index (APRI) (1.3 vs 1.0, P < 0.001), and liver stiffness measurements (LSM) (9.5 vs 4.6, P < 0.001) were significantly different after G/P treatment. CONCLUSIONS Regardless of genotype, G/P treatment for Koreans with CHC is safe, highly effective, and can improve liver fibrosis.
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22
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Kosloski MP, Li H, Wang S, Mensa F, Kort J, Liu W. Characterizing complex and competing drug-drug interactions between the antiviral regimen of glecaprevir and pibrentasvir with rifampin or carbamazepine. Clin Transl Sci 2023; 16:593-605. [PMID: 36597378 PMCID: PMC10087067 DOI: 10.1111/cts.13471] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 12/12/2022] [Accepted: 12/16/2022] [Indexed: 01/05/2023] Open
Abstract
The fixed-dose combination of the direct acting antivirals glecaprevir (GLE) and pibrentasvir (PIB) is an oral, once-daily treatment for all six major genotypes of chronic hepatitis C virus infection. A single and multiple-dose rifampin study (N = 12) and a carbamazepine study (N = 12) were conducted in healthy subjects to evaluate the effects of CYP3A/P-gp induction and OATP inhibition on the pharmacokinetics of GLE and PIB. In study 1, GLE 300 mg + PIB 120 mg was administered as a single dose either alone, after single and multiple daily doses of rifampin 600 mg, or 24 h after the last rifampin dose. In study 2, GLE 300 mg + PIB 120 mg was administered as a single dose either alone or after multiple doses of carbamazepine 200 mg. Relative to GLE + PIB alone, exposure of GLE was significantly increased by the first co-administered rifampin dose due to OATP inhibition, significantly decreased 24 h after the last rifampin dose due to CYP3A/P-gp induction, and slightly increased when co-administered with steady-state rifampin due to a combination of inhibition and induction forces. Exposure of PIB was not affected when co-administered with the first rifampin dose but was significantly decreased with steady-state rifampin co-administration, or 24 h after the last rifampin dose due to P-gp induction. Carbamazepine significantly decreased GLE and PIB exposure, mainly attributed to P-gp induction. The regimens tested were generally well-tolerated by the subjects and no new safety issues were identified.
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Affiliation(s)
| | - Hong Li
- Data and Statistical Sciences, AbbVie Inc., North Chicago, Illinois, USA
| | - Stanley Wang
- Infectious Disease, AbbVie Inc., North Chicago, Illinois, USA
| | - Federico Mensa
- Infectious Disease, AbbVie Inc., North Chicago, Illinois, USA
| | - Jens Kort
- Medical Affairs, AbbVie Inc., North Chicago, Illinois, USA
| | - Wei Liu
- Clinical Pharmacology, AbbVie Inc., North Chicago, Illinois, USA
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23
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Soriano V, Moreno-Torres V, Treviño A, Barreiro P, de Jesus F, Corral O, de Mendoza C. Safety considerations in the management of hepatitis C and HIV co-infection. Expert Opin Drug Saf 2023; 22:363-372. [PMID: 37096834 DOI: 10.1080/14740338.2023.2206647] [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: 01/25/2023] [Accepted: 04/20/2023] [Indexed: 04/26/2023]
Abstract
INTRODUCTION Both HCV and HIV are highly prevalent infections with current estimates of 57 and 38 million people infected worldwide, respectively. Oral antivirals can be curative for HCV and rescue HIV patients from disease progression. Dual therapy in coinfected patients requires expertise. AREAS COVERED Four major issues challenge dual HCV and HIV treatment, including overlapping drug-related side effects, hepatitis B reactivation, immune reconstitution inflammatory syndromes (IRIS), and drug-drug interactions (DDI). A search was conducted in PubMed from January 2010 to March 2023. EXPERT OPINION The advent of second-generation direct-acting antivirals (DDA) that depict higher antiviral potency, fewer side effects, pangenotypic activity and are co-formulated has expanded the indication of HCV therapy and particularly in HIV-coinfected individuals. Sequential initiation of antiretrovirals (ARV) followed by DAA is generally preferred to start dual treatment concomitantly. Close monitoring of rare episodes of HBV reactivation and IRIS is warranted. The most frequent DDI between DAA and ARV affect drug metabolism by CYP450 induction/inhibition, leading to abnormal drug exposures. Throughout this mechanism interact most HCV and HIV protease inhibitors and non-nucleoside polymerase inhibitors. Exposure to some HIV and HCV nucleos(t)ide analogues (e.g. tenofovir and sofosbuvir, respectively) is subject to induction/inhibition of drug transporters and requires special attention in patients with renal insufficiency.
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Affiliation(s)
- Vicente Soriano
- Health Sciences School & Medical Center, Universidad Internacional La Rioja (UNIR), Madrid, Spain
| | - Víctor Moreno-Torres
- Health Sciences School & Medical Center, Universidad Internacional La Rioja (UNIR), Madrid, Spain
- Department of Internal Medicine, Puerta de Hierro University Hospital & Research Institute, Majadahonda, Madrid, Spain
| | - Ana Treviño
- Health Sciences School & Medical Center, Universidad Internacional La Rioja (UNIR), Madrid, Spain
| | - Pablo Barreiro
- Health Sciences School & Medical Center, Universidad Internacional La Rioja (UNIR), Madrid, Spain
- Infctious Diseases Unit, Emergency Hospital Enfermera Isabel Zendal, Madrid, Spain
| | - Fernando de Jesus
- Health Sciences School & Medical Center, Universidad Internacional La Rioja (UNIR), Madrid, Spain
| | - Octavio Corral
- Health Sciences School & Medical Center, Universidad Internacional La Rioja (UNIR), Madrid, Spain
| | - Carmen de Mendoza
- Department of Internal Medicine, Puerta de Hierro University Hospital & Research Institute, Majadahonda, Madrid, Spain
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24
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Feld JJ, Forns X, Dylla DE, Kumada H, de Ledinghen V, Wei L, Brown RS, Flisiak R, Lampertico P, Thabut D, Bondin M, Tatsch F, Burroughs M, Marcinak J, Zhang Z, Emmett A, Jacobson IM. Safety analysis of glecaprevir/pibrentasvir in patients with markers of advanced liver disease in clinical and real-world cohorts. J Viral Hepat 2022; 29:1050-1061. [PMID: 36036117 PMCID: PMC9827821 DOI: 10.1111/jvh.13738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 04/28/2022] [Accepted: 07/06/2022] [Indexed: 01/18/2023]
Abstract
Chronic hepatitis C virus (HCV) infection has the greatest health impact in patients with advanced liver disease. The direct-acting antiviral (DAA) regimen glecaprevir/pibrentasvir (G/P) is approved for treatment of HCV-infected patients without cirrhosis and with compensated cirrhosis. However, events of liver decompensation/failure have been reported in patients treated with protease-inhibitor-containing DAA regimens, often in patients with advanced liver disease. This study examines the safety of on-label G/P treatment in patients with compensated cirrhosis (F4 at baseline) with markers of advanced liver disease. Patients with cirrhosis were categorized into 4 subgroups, based on different noninvasive markers of advanced liver disease identified using laboratory measures: platelet count < or ≥ 100 × 109 /L, and Child-Pugh score 5 or 6. Separate analyses were performed using pooled data from clinical trials and from real-world post-marketing observational studies. G/P was well tolerated in patients with platelet count ≥100 × 109 /L (n = 800), platelet count <100 × 109 /L (n = 215), a Child-Pugh score of 5 (n = 915) and a Child-Pugh score of 6 (n = 95). In the clinical trial and real-world cohorts two patients and no patients experienced a serious adverse event (AE) possibly related to study drug, respectively; three patients and no patients experienced an AE of special interest for hepatic decompensation and hepatic failure. This analysis reaffirms G/P's safety profile in indicated patients with compensated cirrhosis, including those with markers of more advanced liver disease. Increasing the number of patients treated with short-duration G/P therapy may contribute to meeting HCV elimination targets.
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Affiliation(s)
- Jordan J. Feld
- Toronto Centre for Liver DiseaseUniversity Health Network, University of TorontoTorontoOntarioCanada
| | - Xavier Forns
- Liver Unit, Hospital ClinicUniversity of Barcelona, IDIBAPS and CIBEREHDBarcelonaSpain
| | | | | | | | - Lai Wei
- Peking University People's HospitalPeking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseaseBeijingChina,Beijing Tsinghua Changgung HospitalTsinghua UniversityBeijingChina
| | - Robert S. Brown
- Center for Liver Disease and TransplantationWeill Cornell Medical CollegeNew YorkNew YorkUSA
| | - Robert Flisiak
- Department of Infectious Diseases and HepatologyMedical University of Białystok, BiałystokBialystokPoland
| | - Pietro Lampertico
- Division of Gastroenterology and HepatologyFoundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, CRC “A. M. and A. Migliavacca” Center for Liver DiseaseMilanItaly,Department of Pathophysiology and TransplantationUniversity of MilanMilanItaly
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25
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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.
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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
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26
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Wang AE, Hsieh E, Turner BJ, Terrault N. Integrating Management of Hepatitis C Infection into Primary Care: the Key to Hepatitis C Elimination Efforts. J Gen Intern Med 2022; 37:3435-3443. [PMID: 35484367 PMCID: PMC9551010 DOI: 10.1007/s11606-022-07628-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 04/18/2022] [Indexed: 11/24/2022]
Abstract
Elimination of hepatitis C virus (HCV), a leading cause of liver disease in the USA and globally, has been made possible with the advent of highly efficacious direct acting antivirals (DAAs). DAA regimens offer cure of HCV with 8-12 weeks of a well-tolerated once daily therapy. With increasingly straightforward diagnostic and treatment algorithms, HCV infection can be managed not only by specialists, but also by primary care providers. Engaging primary care providers greatly increases capacity to diagnose and treat chronic HCV and ultimately make HCV elimination a reality. However, barriers remain at each step in the HCV cascade of care from screening to evaluation and treatment. Since primary care is at the forefront of patient contact, it represents the ideal place to concentrate efforts to identify barriers and implement solutions to achieve universal HCV screening and increase curative treatment.
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Affiliation(s)
- Allison E Wang
- Department of Internal Medicine, University of Southern California, Los Angeles, CA, USA
| | - Eric Hsieh
- Department of Internal Medicine, University of Southern California, Los Angeles, CA, USA
| | - Barbara J Turner
- Department of Internal Medicine, University of Southern California, Los Angeles, CA, USA
| | - Norah Terrault
- Department of Internal Medicine, University of Southern California, Los Angeles, CA, USA.
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, University of Southern California, Los Angeles, CA, USA.
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27
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Kiattanaphon A, Vipsoongnern Y, Kunthalert D, Sistayanarain A. Partial nonstructural 3 region analysis of hepatitis C virus genotype 3a. Mol Biol Rep 2022; 49:9437-9443. [PMID: 36002650 DOI: 10.1007/s11033-022-07803-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 07/07/2022] [Accepted: 07/08/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND The hepatitis C virus (HCV) is a major cause of illness around the world. HCV genotype 3a is the most prevalent genotype in Thailand. Direct-acting antiviral (DAA) drugs are available for treatment, and these drugs target the NS3, NS5A, and NS5b proteins of HCV. However, HCV variants that are resistant to NS3 protease inhibitors have been found during treatment. This resistance can be naturally occurring or in response to treatment. The purpose of this study is to analyze the codon positions of the main mutation of the partial NS3 gene region of HCV genotype 3a. METHODS In order to detect mutations and confirm the genotype of HCV genotype 3a, the nucleotide sequencing and amino acid portion of NS3 were analyzed. RESULTS Twenty-six samples were successfully sequenced and clustered within two sub-clades defined as 3a-1 and 3a-2. Through amino acid mutation analysis, the variations were detected at codon positions 122 (3.8%), 132 (84.6%), 168 (100%), 170 (92.3%), 174 (100%), and 175 (100%). CONCLUSIONS In conclusion, mutations at positions 168, 170, 174, and 175 of the NS3 region are common within the HCV genotype 3a. This information should be useful in the development of effective anti-viral drugs that can successfully treat HCV infection.
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Affiliation(s)
- Anusorn Kiattanaphon
- Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand
| | | | - Duangkamol Kunthalert
- Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand
| | - Anchalee Sistayanarain
- Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand.
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28
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Shah R, Barclay ST, Peters ES, Fox R, Gunson R, Bradley-Stewart A, Shepherd SJ, MacLean A, Tong L, van Vliet VJE, Ngan Chiu Bong M, Filipe A, Thomson EC, Davis C. Characterisation of a Hepatitis C Virus Subtype 2a Cluster in Scottish PWID with a Suboptimal Response to Glecaprevir/Pibrentasvir Treatment. Viruses 2022; 14:v14081678. [PMID: 36016300 PMCID: PMC9416734 DOI: 10.3390/v14081678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 07/21/2022] [Accepted: 07/27/2022] [Indexed: 11/16/2022] Open
Abstract
Direct-acting antivirals (DAAs) have revolutionised the treatment of Hepatitis C virus (HCV), allowing the World Health Organisation (WHO) to set a target of eliminating HCV by 2030. In this study we aimed to investigate glecaprevir and pibrentasvir (GP) treatment outcomes in a cohort of patients with genotype 2a infection. METHODS Clinical data and plasma samples were collected in NHS Greater Glasgow & Clyde. Next generation whole genome sequencing and replicon assays were carried out at the MRC-University of Glasgow Centre for Virus Research. RESULTS 132 cases infected with genotype 2a HCV were identified. The SVR rate for this group was 91% (112/123) following treatment with GP. An NS5A polymorphism, L31M, was detected in all cases of g2a infection, and L31M+R353K in individuals that failed treatment. The results showed that R353K was present in 90% of individuals in the Glasgow genotype 2a phylogenetic cluster but in less than 5% of all HCV subtype 2a published sequences. In vitro efficacy of pibrentasvir against sub-genomic replicon constructs containing these mutations showed a 2-fold increase in IC50 compared to wildtype. CONCLUSION This study describes a cluster of HCV genotype 2a infection associated with a lower-than-expected SVR rate following GP treatment in association with the NS5A mutations L31M+R353K.
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Affiliation(s)
- Rajiv Shah
- Thomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK; (R.G.); (L.T.); (V.J.E.v.V.); (M.N.C.B.); (A.F.); (E.C.T.)
- Correspondence: (R.S.); (C.D.)
| | - Stephen T. Barclay
- NHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UK; (S.T.B.); (E.S.P.); (R.F.); (A.B.-S.); (S.J.S.); (A.M.)
| | - Erica S. Peters
- NHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UK; (S.T.B.); (E.S.P.); (R.F.); (A.B.-S.); (S.J.S.); (A.M.)
| | - Ray Fox
- NHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UK; (S.T.B.); (E.S.P.); (R.F.); (A.B.-S.); (S.J.S.); (A.M.)
| | - Rory Gunson
- Thomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK; (R.G.); (L.T.); (V.J.E.v.V.); (M.N.C.B.); (A.F.); (E.C.T.)
- NHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UK; (S.T.B.); (E.S.P.); (R.F.); (A.B.-S.); (S.J.S.); (A.M.)
| | - Amanda Bradley-Stewart
- NHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UK; (S.T.B.); (E.S.P.); (R.F.); (A.B.-S.); (S.J.S.); (A.M.)
| | - Samantha J. Shepherd
- NHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UK; (S.T.B.); (E.S.P.); (R.F.); (A.B.-S.); (S.J.S.); (A.M.)
| | - Alasdair MacLean
- NHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UK; (S.T.B.); (E.S.P.); (R.F.); (A.B.-S.); (S.J.S.); (A.M.)
| | - Lily Tong
- Thomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK; (R.G.); (L.T.); (V.J.E.v.V.); (M.N.C.B.); (A.F.); (E.C.T.)
| | - Vera Jannie Elisabeth van Vliet
- Thomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK; (R.G.); (L.T.); (V.J.E.v.V.); (M.N.C.B.); (A.F.); (E.C.T.)
| | - Michael Ngan Chiu Bong
- Thomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK; (R.G.); (L.T.); (V.J.E.v.V.); (M.N.C.B.); (A.F.); (E.C.T.)
| | - Ana Filipe
- Thomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK; (R.G.); (L.T.); (V.J.E.v.V.); (M.N.C.B.); (A.F.); (E.C.T.)
| | - Emma C. Thomson
- Thomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK; (R.G.); (L.T.); (V.J.E.v.V.); (M.N.C.B.); (A.F.); (E.C.T.)
- NHS Greater Glasgow & Clyde, Departments of Hepatology and Virology, Glasgow Royal Infirmary, Glasgow G4 0SF, UK; (S.T.B.); (E.S.P.); (R.F.); (A.B.-S.); (S.J.S.); (A.M.)
| | - Chris Davis
- Thomson Group, College of Medical, Veterinary & Life Sciences, MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK; (R.G.); (L.T.); (V.J.E.v.V.); (M.N.C.B.); (A.F.); (E.C.T.)
- Correspondence: (R.S.); (C.D.)
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Gonzalez-Serna A, Macias J, Corma-Gomez A, Tellez F, Cucurull J, Real LM, Granados R, Rivero-Juarez A, Hernandez-Quero J, Merino D, Palacios R, Rios MJ, Collado A, Pineda JA. High efficacy of glecaprevir/pibrentasvir for HCV-infected individuals with active drug use. J Infect 2022; 85:322-326. [PMID: 35700867 DOI: 10.1016/j.jinf.2022.06.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 06/03/2022] [Accepted: 06/07/2022] [Indexed: 12/21/2022]
Abstract
OBJECTIVES Real world data on glecaprevir/pibrentasvir (G/P) among active drug users are scarce. We evaluated the sustained virological response (SVR) rates of G/P among individuals with and without active drug use in routine clinical practice. METHODS Two ongoing prospective multicenter cohorts of individuals starting G/P were analyzed. Overall SVR intention-to-treat (ITT), discontinuations due to adverse effects and dropouts were evaluated. Results in patients with active, past and without active drug use were compared. RESULTS Overall, 644 individuals started G/P and have reached the date of SVR evaluation. Of them, 613 (95.2%) individuals achieved SVR. There were two (0.3%) relapses, one (0.2%) discontinuation due to side effects and 35 (5.4%) dropouts. SVR rates for patients with active drug use, past drug use and those who never used drugs were 85.4%(n/N = 70/82), 96.1%(n/N = 320/333) and 97.4%(n/N = 223/229) respectively (p < 0.001). After adjustment by sex, age, HCV genotype and opioid agonist therapy, active drug use was the only factor independently associated with SVR (ITT) [adjusted OR (95%confidence interval): 0.29(0.09-0.99),p = 0.048]. CONCLUSIONS Active drug use was independently associated with lower SVR rates to G/P, mainly due to voluntary dropout. G/P could be particularly beneficial in this scenario but specific strategies designed to increase the retention in care are needed.
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Affiliation(s)
- Alejandro Gonzalez-Serna
- Hospital Universitario de Valme, Seville, Spain; Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain; Instituto de Biomedicina de Sevilla (IBiS), Sevilla, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Spain; Grupo Estudio Hepatitis Víricas (GEHEP) de la SEIMC. GEHEP-001
| | - Juan Macias
- Hospital Universitario de Valme, Seville, Spain; Instituto de Biomedicina de Sevilla (IBiS), Sevilla, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Spain; Departamento de Medicina, Universidad de Sevilla, Sevilla, Spain; Grupo Estudio Hepatitis Víricas (GEHEP) de la SEIMC. GEHEP-001.
| | - Anaïs Corma-Gomez
- Hospital Universitario de Valme, Seville, Spain; Instituto de Biomedicina de Sevilla (IBiS), Sevilla, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Spain; Grupo Estudio Hepatitis Víricas (GEHEP) de la SEIMC. GEHEP-001
| | - Francisco Tellez
- Hospital Universitario de Puerto Real, Puerto Real, Spain; Grupo Estudio Hepatitis Víricas (GEHEP) de la SEIMC. GEHEP-001
| | - Josep Cucurull
- Fundacio Salut Emporda (Fundació Privada), Figueres, Spain; Grupo Estudio Hepatitis Víricas (GEHEP) de la SEIMC. GEHEP-001
| | - Luis M Real
- Hospital Universitario de Valme, Seville, Spain; Instituto de Biomedicina de Sevilla (IBiS), Sevilla, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Spain; Departamento de Especialidades Quirúrgicas, Bioquímica e Inmunología. Facultad de Medicina, Universidad de Málaga, Málaga, Spain; Grupo Estudio Hepatitis Víricas (GEHEP) de la SEIMC. GEHEP-001
| | - Rafael Granados
- Hospital de Gran Canaria Dr. Negrín, Las Palmas de Gran Canarias, Spain; Grupo Estudio Hepatitis Víricas (GEHEP) de la SEIMC. GEHEP-001
| | - Antonio Rivero-Juarez
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Spain; Instituto Maimonides de Investigación Biomedica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Córdoba, Spain; Grupo Estudio Hepatitis Víricas (GEHEP) de la SEIMC. GEHEP-001
| | - José Hernandez-Quero
- Hospital Universitario de San Cecilio de Granada, Granada, Spain; Grupo Estudio Hepatitis Víricas (GEHEP) de la SEIMC. GEHEP-001
| | - Dolores Merino
- Hospital Juan Ramón Jiménez, Huelva, Spain; Grupo Estudio Hepatitis Víricas (GEHEP) de la SEIMC. GEHEP-001
| | - Rosario Palacios
- Hospital Clínico Universitario Virgen de la Victoria, Málaga, Spain; Grupo Estudio Hepatitis Víricas (GEHEP) de la SEIMC. GEHEP-001
| | - Maria José Rios
- Hospital Universitario Virgen Macarena, Sevilla, Spain; Grupo Estudio Hepatitis Víricas (GEHEP) de la SEIMC. GEHEP-001
| | - Antonio Collado
- Hospital Universitario Torrecárdenas, Almería, Spain; Grupo Estudio Hepatitis Víricas (GEHEP) de la SEIMC. GEHEP-001
| | - Juan A Pineda
- Hospital Universitario de Valme, Seville, Spain; Instituto de Biomedicina de Sevilla (IBiS), Sevilla, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Spain; Departamento de Medicina, Universidad de Sevilla, Sevilla, Spain; Grupo Estudio Hepatitis Víricas (GEHEP) de la SEIMC. GEHEP-001
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Hatanaka T, Kakizaki S, Kaburagi T, Saito N, Nakano S, Hazama Y, Yoshida S, Hachisu Y, Tanaka Y, Yoshinaga T, Kashiwabara K, Naganuma A, Yamazaki Y, Uraoka T, Nagashima S, Takahashi M, Nishizawa T, Murata K, Okamoto H. Chronic Infection with Hepatitis C Virus Subtype 1g in a Japanese Patient Successfully Treated with Glecaprevir/Pibrentasvir. Intern Med 2022; 61:1537-1543. [PMID: 34897154 PMCID: PMC9177357 DOI: 10.2169/internalmedicine.8673-21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 10/27/2021] [Indexed: 11/09/2022] Open
Abstract
A 66-year-old man, who had undergone plasma exchange 30 years previously in Egypt for the treatment of falciparum malaria, was referred to our hospital for treatment of chronic hepatitis C (HCV). An analysis of the 655-nucleotide 5'-untranslated region-core region sequence revealed infection with HCV subtype 1g. A phylogenetic analysis of the full-length HCV genome confirmed that the patient's HCV was subtype 1g, which was the first case identified in Japan. Although his HCV possessed several naturally occurring resistance-associated substitutions in the nonstructural (NS) 3 and NS5A regions, he was successfully treated by combination therapy with glecaprevir/pibrentasvir.
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Affiliation(s)
- Takeshi Hatanaka
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Japan
| | - Satoru Kakizaki
- Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Japan
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Japan
| | - Takuya Kaburagi
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Japan
| | - Naoto Saito
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Japan
| | - Sachi Nakano
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Japan
| | - Yoichi Hazama
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Japan
| | - Sachiko Yoshida
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Japan
| | - Yoko Hachisu
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Japan
| | - Yoshiki Tanaka
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Japan
| | - Teruo Yoshinaga
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Japan
| | | | - Atsushi Naganuma
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Japan
| | - Yuichi Yamazaki
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Japan
| | - Toshio Uraoka
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Japan
| | - Shigeo Nagashima
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Japan
| | - Masaharu Takahashi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Japan
| | - Tsutomu Nishizawa
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Japan
| | - Kazumoto Murata
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Japan
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Japan
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31
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Chen JJ, Chiu YC, Lee PL, Tung HD, Chiu HC, Chien SC, Cheng PN. Real-world effectiveness and safety of sofosbuvir/velpatasvir and glecaprevir/pibrentasvir for genotype 6 chronic hepatitis C. J Formos Med Assoc 2022; 121:2265-2272. [PMID: 35581112 DOI: 10.1016/j.jfma.2022.04.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 04/25/2022] [Accepted: 04/28/2022] [Indexed: 12/29/2022] Open
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Takaura K, Kurosaki M, Inada K, Kirino S, Yamashita K, Muto T, Osawa L, Sekiguchi S, Hayakawa Y, Higuchi M, Kaneko S, Maeyashiki C, Tamaki N, Yasui Y, Itakura J, Tsuchiya K, Nakanishi H, Takahashi Y, Izumi N. The impact of background liver disease on the long-term prognosis of very-early-stage HCC after ablation therapy. PLoS One 2022; 17:e0264075. [PMID: 35196341 PMCID: PMC8865683 DOI: 10.1371/journal.pone.0264075] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 02/02/2022] [Indexed: 12/24/2022] Open
Abstract
Background and aim The long-term prognosis of hepatocellular carcinoma (HCC) treated at a very-early-stage (the Barcelona Clinical Liver Cancer (BCLC) classification stage 0) was unclear, especially in terms of background liver disease. Methods This single-center, retrospective study included 302 patients with BCLC stage 0 HCC treated with radiofrequency ablation (RFA) and followed for at least six months. We examined the impact of background liver disease on overall survival and recurrence. Results The median age was 72 (range; 36–91) years; the median tumor diameter was 15 (range; 8–20) mm. The etiologies of background liver disease were hepatitis B virus infection (HBV) in 24 cases, hepatitis C virus infection (HCV) in 195 cases, and non-viral (NBNC) in 83 cases. Among the patients with HCV, 63 had achieved sustained virological response (SVR) by antiviral therapy (HCV SVR) before developing HCC (n = 37) or after HCC treatment (n = 26), and 132 had active HCV infection (HCV non-SVR). The median overall survival was 85 (95% CI; 72–98) months, and the median recurrence-free survival was 26 (95% CI; 20–30) months. Active infection with hepatitis C virus negatively contributed to overall survival (HR 2.91, 95% CI 1.31–3.60, p = 0.003) and recurrence-free survival (HR 1.47, 95% CI 1.06–2.05, p = 0.011). Conclusions The prognosis of RFA treatment for very early-stage HCC was favorable. Achieving SVR in hepatitis C was important for further prognosis improvement.
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Affiliation(s)
- Kenta Takaura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kento Inada
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Sakura Kirino
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kouji Yamashita
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Tomohiro Muto
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Leona Osawa
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Shuhei Sekiguchi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yuka Hayakawa
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Mayu Higuchi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Shun Kaneko
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Chiaki Maeyashiki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
- Division of Medicine, NAFLD Research Center, University of California, San Diego, La Jolla, California, United States of America
| | - Yutaka Yasui
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Jun Itakura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kaoru Tsuchiya
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Hiroyuki Nakanishi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yuka Takahashi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
- * E-mail:
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Hepatitis C virus eradication prolongs overall survival in hepatocellular carcinoma patients receiving molecular-targeted agents. J Gastroenterol 2022; 57:90-98. [PMID: 35031857 DOI: 10.1007/s00535-021-01837-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 11/13/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND The aim of this multicenter retrospective study was to evaluate the impact of the eradication of hepatitis C virus (HCV) on the clinical outcomes of patients with hepatocellular carcinoma (HCC) treated with molecular-targeted agents (MTAs). METHODS Among 877 patients who received any MTA as first-line systemic therapy for HCC between June 2009 and March 2019, 569 patients with HCV-related HCC were enrolled in this retrospective study. Of these, 109 patients achieved sustained virological response (SVR) before starting MTA. After propensity score matching, the clinical outcomes of 109 patients in the SVR group and 109 patients in the non-SVR group were compared. RESULTS The median time to progression in the SVR group (7.8 months) was similar to that in the non-SVR group (5.6 months) (p = 0.212). The median time to treatment failure in the SVR group (5.3 months) was longer than that in the non-SVR group (2.8 months) (p = 0.059), and post-progression survival and overall survival in the SVR group were significantly longer than those in the non-SVR group (12.0 months vs 7.2 months; p = 0.039, and 18.1 months vs 11.3 months; p = 0.019). At the end of first-line MTA therapy, the albumin-bilirubin (ALBI) score in the SVR group ( - 2.25) was significantly lower than that in the non-SVR group ( - 2.10) (p = 0.008). CONCLUSIONS The eradication of HCV before MTA therapy maintained liver function and led to a prolonged treatment period and improved overall survival of HCV-related HCC patients. We should not overlook the benefits of HCV eradication in HCC patients.
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Churkin A, Kriss S, Uziel A, Goyal A, Zakh R, Cotler SJ, Etzion O, Shlomai A, Rotstein HG, Dahari H, Barash D. Machine learning for mathematical models of HCV kinetics during antiviral therapy. Math Biosci 2022; 343:108756. [PMID: 34883104 PMCID: PMC8792269 DOI: 10.1016/j.mbs.2021.108756] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 11/04/2021] [Accepted: 11/04/2021] [Indexed: 01/03/2023]
Abstract
Mathematical models for hepatitis C virus (HCV) dynamics have provided a means for evaluating the antiviral effectiveness of therapy and estimating treatment outcomes such as the time to cure. Recently, a mathematical modeling approach was used in the first proof-of-concept clinical trial assessing in real-time the utility of response-guided therapy with direct-acting antivirals (DAAs) in chronic HCV-infected patients. Several retrospective studies have shown that mathematical modeling of viral kinetics predicts time to cure of less than 12 weeks in the majority of individuals treated with sofosbuvir-based as well as other DAA regimens. A database of these studies was built, and machine learning methods were evaluated for their ability to estimate the time to cure for each patient to facilitate real-time modeling studies. Data from these studies exploring mathematical modeling of HCV kinetics under DAAs in 266 chronic HCV-infected patients were gathered. Different learning methods were applied and trained on part of the dataset ('train' set), to predict time to cure on the untrained part ('test' set). Our results show that this machine learning approach provides a means for establishing an accurate time to cure prediction that will support the implementation of individualized treatment.
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Affiliation(s)
- Alexander Churkin
- Department of Software Engineering, Sami Shamoon College of Engineering, Beer-Sheba, Israel
| | - Stephanie Kriss
- Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA
| | - Asher Uziel
- Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA
| | - Ashish Goyal
- Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA
| | - Rami Zakh
- Department of Computer Science, Ben-Gurion University, Israel
| | - Scott J Cotler
- Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA
| | - Ohad Etzion
- Soroka University Medical Center, Beer-Sheba, Israel
| | - Amir Shlomai
- Department of Medicine D and The Liver Institute, Rabin Medical Center, Beilinson Hospital, Petah-Tikva and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Horacio G Rotstein
- Federated Department of Biological Sciences, New Jersey Institute of Technology and Rutgers University, Newark, NJ, USA; Institute for Future Technologies, New Jersey Institute of Technology, Newark, NJ, USA
| | - Harel Dahari
- Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.
| | - Danny Barash
- Department of Computer Science, Ben-Gurion University, Israel.
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Tien A, Sahota A, Yang SJ, Balbuena R, Chang M, Lim C, Fong TL. Prevalence and Characteristics of Chronic Hepatitis C Among Asian Americans Are Distinct From Other Ethnic Groups. J Clin Gastroenterol 2021; 55:884-890. [PMID: 33074947 DOI: 10.1097/mcg.0000000000001447] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 09/12/2020] [Indexed: 01/22/2023]
Abstract
GOAL The goal of this study was to determine the prevalence and characteristics of chronic hepatitis C (CHC) among Asian Americans compared with other ethnicities. BACKGROUND Chronic hepatitis C virus (HCV) affects an estimated 2.7 million in the United States, but there are limited data on HCV among Asian Americans. STUDY A total of 3,369,881 adults over the age of 18 who were patients of the integrated health care system in Southern California and 4903 Asian participants at community hepatitis screenings were included in a cross-sectional study. Variables included HCV serology, HCV genotype, comorbidities, and coinfections. RESULTS The prevalence of CHC was 1.3% in the general population (8271 adults) and 0.6% among Asians. The prevalence of CHC was significantly higher in the 1945-1965 birth cohort with 2.7% (5876) in the general population and 1.0% (313) among Asians (P<0.001). Asians had the highest rates of hepatitis B coinfection (2.9% vs. 0.2%, P<0.001). The distribution of genotypes among Asians differed from the general population with the most common genotype being 1b (27.5%) and a higher presence of genotype 6 (9.5%) (P<0.001). The presence of cirrhosis was 17.6% in Asians. Disaggregated Asian data showed that CHC was highest among Vietnamese and Cambodian and that genotype 6 was predominant among these 2 subgroups. CONCLUSIONS The prevalence of chronic HCV was significantly lower in Asians compared with other ethnicities. However, disaggregated data among Asians showed the highest prevalence rates among adults from Vietnam and Cambodia.
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Affiliation(s)
| | - Amandeep Sahota
- Gastroenterology, Kaiser Permanente Los Angeles Medical Center
| | - Su-Jau Yang
- Department of Research and Evaluation, Southern California Kaiser Permanente, Pasadena, CA
| | - Ronald Balbuena
- Department of Research and Evaluation, Southern California Kaiser Permanente, Pasadena, CA
| | - Mimi Chang
- Asian Pacific Liver Center, St. Vincent Medical Center
| | - Carolina Lim
- Asian Pacific Liver Center, St. Vincent Medical Center
| | - Tse-Ling Fong
- Asian Pacific Liver Center, St. Vincent Medical Center
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine at University of Southern California, Los Angeles
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Edmonds C, Carver A, DeClercq J, Choi L, Peter M, Schlendorf K, Perri R, Forbes RC, Concepcion BP. Access to hepatitis C direct-acting antiviral therapy in hepatitis C-positive donor to hepatitis C-negative recipient solid-organ transplantation in a real-world setting. Am J Surg 2021; 223:975-982. [PMID: 34548142 DOI: 10.1016/j.amjsurg.2021.09.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2021] [Revised: 08/20/2021] [Accepted: 09/06/2021] [Indexed: 01/08/2023]
Abstract
BACKGROUND Emerging data supports expanding the solid organ donor pool with transplantation from hepatitis C virus (HCV)-positive donors into HCV-negative recipients. However, concerns exist regarding the ability to access direct-acting antivirals (DAAs) post-transplant in a real-world setting. METHODS This single-center, retrospective study evaluated DAA access rates, time to first dose, and patient cost in donor-derived HCV solid-organ transplant recipients utilizing an integrated specialty pharmacy process. RESULTS Among 91 patients, all accessed DAAs through prescription insurance (97%) or patient assistance programs (3%). Of those who received DAAs through insurance, only 65% received approval on initial insurance submission. Median time from transplant to first dose was 45d [IQR 34-66]. The on-site specialty pharmacy was used by 69% of patients. Copay assistance programs reduced the median monthly patient cost from $1914 [range $7-7536] to $0 [range $0-5]. CONCLUSION Our findings indicate that access to DAAs in donor-derived HCV post-transplant is achievable and affordable; however, significant added administrative efforts may be required for insurance approval as well as obtaining copay assistance, which is a limited resource.
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Affiliation(s)
- Cori Edmonds
- Vanderbilt Specialty Pharmacy, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Alicia Carver
- Vanderbilt Specialty Pharmacy, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Josh DeClercq
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Leena Choi
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Megan Peter
- Vanderbilt Specialty Pharmacy, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Kelly Schlendorf
- Section of Heart Failure and Cardiac Transplantation, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Roman Perri
- Department of Medicine, Division of Hepatology, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Rachel C Forbes
- Department of Surgery, Division of Kidney and Pancreas Transplantation, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Beatrice P Concepcion
- Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN, USA.
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Feldman TC, Dienstag JL, Mandl KD, Tseng YJ. Machine-learning-based predictions of direct-acting antiviral therapy duration for patients with hepatitis C. Int J Med Inform 2021; 154:104562. [PMID: 34482150 DOI: 10.1016/j.ijmedinf.2021.104562] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 08/15/2021] [Accepted: 08/16/2021] [Indexed: 02/09/2023]
Abstract
INTRODUCTION Hepatitis C, which affects 71 million persons worldwide, is the most common blood-borne pathogen in the United States. Chronic infections can be treated effectively thanks to the availability of modern direct-acting antiviral (DAA) therapies. Real-world data on the duration of DAA therapy, which can be used to optimize and guide the course of therapy, may also be useful in determining quality of life enhancements based upon total required supply of medication and long-term improvements to quality of life. We developed a machine learning model to identify patient characteristics associated with prolonged DAA treatment duration. METHODS A nationwide U.S. commercial managed care plan with claims data that covers about 60 million beneficiaries from 2009 to 2019 were used in the retrospective study. We examined differences in age, gender, and multiple comorbidities among patients treated with different durations of DAA treatment. We also examined the performance of machine learning models for predicting a prolonged course of DAA based on the area under the receiver operating characteristic curve (AUC). RESULTS We identified 3943 cases with hepatitis C who received sofosbuvir/ledipasvir as the first course of DAA and were eligible for the study. Patients receiving prolonged treatment (n = 240, 6.1%) were more likely to have compensated cirrhosis, decompensated cirrhosis, and other comorbidities (P < 0.001). For distinguishing patients who received prolonged DAA treatment for hepatitis C from patients received standard treatment, the optimal predictive model, constructed with XGBoost, had an AUC of 0.745 ± 0.031 (P < 0.001). CONCLUSIONS The risk of antiviral resistance and the cost of DAA are strong motivators to ensure that first-round DAA therapy is effective. For the dominant DAA treatment during the course of this analysis, we present a model that identifies factors already captured in established guidelines and adds to those age, comorbidity burden, and type 2 diabetes status; patient characteristics that are predictive of extended treatment.
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Affiliation(s)
- Theodore C Feldman
- Computational Health Informatics Program, Boston Children's Hospital, Boston, MA, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA; VA Boston Healthcare System, Boston, MA, USA
| | - Jules L Dienstag
- Gastrointestinal Unit, Massachusetts Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA
| | - Kenneth D Mandl
- Computational Health Informatics Program, Boston Children's Hospital, Boston, MA, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Yi-Ju Tseng
- Computational Health Informatics Program, Boston Children's Hospital, Boston, MA, USA; Department of Information Management, National Central University, Taoyuan, Taiwan.
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Stanciu C, Muzica CM, Girleanu I, Cojocariu C, Sfarti C, Singeap AM, Huiban L, Chiriac S, Cuciureanu T, Trifan A. An update on direct antiviral agents for the treatment of hepatitis C. Expert Opin Pharmacother 2021; 22:1729-1741. [PMID: 33896315 DOI: 10.1080/14656566.2021.1921737] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 04/21/2021] [Indexed: 02/06/2023]
Abstract
Introduction: The development of direct-acting antiviral (DAA) agents for the treatment of hepatitis C virus (HCV) infection has completely transformed the management of this disease. The advantages of using DAA therapies include high efficacy (sustained virological response (SVR) rate >95%) with minimal side effects, good tolerability, easy drug administration (once daily oral dosing), and short duration of treatment (8-12 weeks). This transformative nature of DAA therapy underpins the goal of the World Health Organization to eliminate HCV infection as a public health threat by 2030.Areas covered: This review seeks to address the current status of DAA therapies, including recent developments, current limitations, and future challenges.Expert opinion: The current DAA regimens, with their high effectiveness and safety profiles, have changed patient perception of HCV infection from a disease that requires complex evaluation and long-term monitoring to a disease that can be cured after one visit to the general practitioner. Despite the remarkably high success rate of DAAs, few patients (4-5%) fail to obtain SVR even after treatment. Five years ahead, the landscape of HCV treatment will undoubtedly continue to evolve, and more pan-genotypic treatment options will be available to all patients.
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Affiliation(s)
- Carol Stanciu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, ST. SpiridonEmergency Hospital, Iasi, Romania
| | - Cristina Maria Muzica
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, ST. SpiridonEmergency Hospital, Iasi, Romania
| | - Irina Girleanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, ST. SpiridonEmergency Hospital, Iasi, Romania
| | - Camelia Cojocariu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, ST. SpiridonEmergency Hospital, Iasi, Romania
| | - Catalin Sfarti
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, ST. SpiridonEmergency Hospital, Iasi, Romania
| | - Ana-Maria Singeap
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, ST. SpiridonEmergency Hospital, Iasi, Romania
| | - Laura Huiban
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, ST. SpiridonEmergency Hospital, Iasi, Romania
| | - Stefan Chiriac
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, ST. SpiridonEmergency Hospital, Iasi, Romania
| | - Tudor Cuciureanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, ST. SpiridonEmergency Hospital, Iasi, Romania
| | - Anca Trifan
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, ST. SpiridonEmergency Hospital, Iasi, Romania
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High Sustained Virologic Response Rates of Glecaprevir/Pibrentasvir in Patients With Dosing Interruption or Suboptimal Adherence. Am J Gastroenterol 2021; 116:1896-1904. [PMID: 34465693 PMCID: PMC8389353 DOI: 10.14309/ajg.0000000000001332] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Accepted: 05/06/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Pangenotypic, all-oral direct-acting antivirals, such as glecaprevir/pibrentasvir (G/P), are recommended for treatment of hepatitis C virus (HCV) infection. Concerns exist about the impact on efficacy in patients with suboptimal adherence, particularly with shorter treatment durations. These post hoc analyses evaluated adherence (based on pill count) in patients prescribed 8- or 12-week G/P, the impact of nonadherence on sustained virologic response at post-treatment week 12 (SVR12), factors associated with nonadherence, and efficacy in patients interrupting G/P treatment. METHODS Data were pooled from 10 phase 3 clinical trials of treatment-naive patients with HCV genotype 1-6 without cirrhosis/with compensated cirrhosis (treatment adherence analysis) and 13 phase 3 clinical trials of all patients with HCV (interruption analysis). RESULTS Among 2,149 patients included, overall mean adherence was 99.4%. Over the treatment duration, adherence decreased (weeks 0-4: 100%; weeks 5-8: 98.3%; and weeks 9-12: 97.1%) and the percentage of patients with ≥80% or ≥90% adherence declined. SVR12 rate in the intention-to-treat (ITT) population was 97.7% (modified ITT SVR12 99.3%) and remained high in nonadherent patients in the modified ITT population (<90%: 94.4%-100%; <80%: 83.3%-100%). Psychiatric disorders were associated with <80% adherence, and shorter treatment duration was associated with ≥80% adherence. Among 2,902 patients in the interruption analysis, 33 (1.1%) had a G/P treatment interruption of ≥1 day, with an SVR12 rate of 93.9% (31/33). No virologic failures occurred. DISCUSSION These findings support the impact of treatment duration on adherence rates and further reinforce the concept of "treatment forgiveness" with direct-acting antivirals.
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Bushman ET, Subramani L, Sanjanwala A, Dionne-Odom J, Franco R, Owen J, Subramaniam A. Pragmatic Experience with Risk-based versus Universal Hepatitis C Screening in Pregnancy: Detection of Infection and Postpartum Linkage to Care. Am J Perinatol 2021; 38:1109-1116. [PMID: 33934324 DOI: 10.1055/s-0041-1728827] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVE Despite the Centers for Disease Control and Prevention (CDC) and U.S. Preventive Services Task Force (USPSTF) recommending universal hepatitis C virus (HCV) screening in pregnancy Society for Maternal-Fetal Medicine (SMFM) and American College of Obstetricians and Gynecologists (ACOG) continue to endorse risk-based screening for HCV in pregnancy. We hypothesized that universal screening is associated with increased HCV diagnosis and postpartum linkage to HCV care compared with risk-based screening. STUDY DESIGN This retrospective cohort study included pregnant women screened for HCV at a single tertiary-care center. We defined two cohorts: women managed with risk-based (January 2014-October 2016) or universal HCV screening (November 2016-December 2018). Screening was performed with ELISA antibody testing and viremia confirmed with HCV ribonucleic acid (RNA) polymerase chain reaction (PCR). Primary outcomes were the rate of HCV screen positivity and postpartum linkage to care. RESULTS From 2014 to 2018, 16,489 women delivered at our institution, of whom 166 screened positive for HCV. A total of 7,039 pregnant women were screened for HCV: 266 with risk-based and 6,773 with universal screening; 29% (76/266) were positive HCV antibody screening (HCVAb + ) in the risk-based cohort and 1.3% (90/6,773) in the universal cohort. HCVAb+ women in the risk-based cohort were more likely to have a positive drug screen. Only 69% (62/90) of HCVAb+ women in the universal cohort met the criteria for risk-based testing. Of the remaining 28 women, 6 (21%) had active viremia (HCV RNA+). Of the 166 HCVAb+ women, 64% (103/166) were HCV RNA+-51 of 266 (19%) in the risk-based and 52 of 6,773 (0.8%) in the universal cohort. Of HCVAb+ women, 75% (125/166) were referred postpartum for HCV evaluation and 27% (34/125) were linked to care. Only 9% (10/103) of women with viremia initiated treatment within 1 year of delivery. CONCLUSION Universal HCV screening in pregnancy identified an additional 31% of HCVAb+ women compared with risk-based screening. Given low rates of HCV follow-up and treatment regardless of screening modality, further studies are needed to address barriers to postpartum linkage to care. KEY POINTS · Ideal screening for HCV in pregnancy is unknown.. · We explore screening strategies in pregnancy to linkage to HCV care.. · Regardless of screening strategy there is low rates of postpartum linkage to HCV care..
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Affiliation(s)
- Elisa T Bushman
- Center for Women's Reproductive Health, University of Alabama at Birmingham, Birmingham, Alabama.,Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Lakshmi Subramani
- University of Alabama Birmingham School of Medicine, Birmingham, Alabama
| | - Aalok Sanjanwala
- Center for Women's Reproductive Health, University of Alabama at Birmingham, Birmingham, Alabama.,Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Jodie Dionne-Odom
- Department of Medicine, University of Alabama Birmingham, Birmingham, Alabama
| | - Ricardo Franco
- Department of Medicine, University of Alabama Birmingham, Birmingham, Alabama
| | - John Owen
- Center for Women's Reproductive Health, University of Alabama at Birmingham, Birmingham, Alabama.,Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Akila Subramaniam
- Center for Women's Reproductive Health, University of Alabama at Birmingham, Birmingham, Alabama.,Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama
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Jhaveri R, Yee LM, Antala S, Murphy M, Grobman WA, Shah SK. Responsible Inclusion of Pregnant Individuals in Eradicating HCV. Hepatology 2021; 74:1645-1651. [PMID: 33743550 DOI: 10.1002/hep.31825] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 03/05/2021] [Accepted: 03/17/2021] [Indexed: 01/08/2023]
Abstract
HCV infections have increased in recent years due to injection drug use and the opioid epidemic. Simultaneously, HCV cure has become a reality, with the advent of direct-acting antivirals (DAAs) and expansion of treatment programs. As a result, HCV screening recommendations now include all adults, including pregnant individuals; and many countries have endorsed widespread DAA access as a strategy to achieve HCV eradication. However, almost universally, pregnant individuals have been systematically excluded from HCV clinical research and treatment programs. This omission runs counter to public health strategies focused on elimination of HCV but is consistent with a historical pattern of exclusion of pregnant individuals from research. Our systematic review of publications on HCV treatment with DAAs in pregnancy revealed only one interventional study, which evaluated sofosbuvir/ledipasvir in 8 pregnant individuals. Given the paucity of research on this issue of great public health importance, we aimed to appraise the current landscape of HCV research/treatment and analyze the ethical considerations for responsibly including pregnant individuals. We propose that pregnancy may be an opportune time to offer HCV treatment given improved access, motivation, and other health care monitoring occurring in the antenatal period. Moreover, treatment of pregnant individuals may support the goal of eliminating perinatal HCV transmission and overcome the established challenges with transitioning care after delivery. The exclusion of pregnant individuals without justification denies them and their offspring access to potential health benefits, raising justice concerns considering growing data on DAA safety and global efforts to promote equitable and comprehensive HCV eradication. Finally, we propose a path forward for research and treatment programs during pregnancy to help advance the goal of HCV elimination.
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Affiliation(s)
- Ravi Jhaveri
- Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL
- Division of Infectious Diseases, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
| | - Lynn M Yee
- Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Swati Antala
- Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL
- Division of Gastroenterology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
| | - Margaret Murphy
- Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL
- Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
| | - William A Grobman
- Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Seema K Shah
- Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL
- Advanced General Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
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42
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Dennis BB, Naji L, Jajarmi Y, Ahmed A, Kim D. New hope for hepatitis C virus: Summary of global epidemiologic changes and novel innovations over 20 years. World J Gastroenterol 2021; 27:4818-4830. [PMID: 34447228 PMCID: PMC8371499 DOI: 10.3748/wjg.v27.i29.4818] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 03/20/2021] [Accepted: 07/13/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is a global health concern associated with significant morbidity and mortality. Before the approval of second-generation direct-acting antiviral agents (DAAs), interferon therapy and liver transplantation constituted the mainstay of treatment. The introduction of well-tolerated oral DAAs in late 2013 has revolutionized HCV management with over 95% cure rates. The predominance of HCV-related liver transplantations has declined following the widespread approval of DAAs. Despite the unparallel efficacy observed among these novel therapies, pharmaceutical costs continue to limit equitable access to healthcare and likely contribute to the differential HCV infection rates observed globally. To reduce the burden of disease worldwide, essential agenda items for all countries must include the prioritization of integrated care models and access to DAAs therapies. Through transparent negotiations with the pharmaceutical industry, the consideration for compassionate release of medications to promote equitable division of care is paramount. Here we provide a literature review of HCV, changes in epidemiologic trends, access issues for current therapies, and global inequities in disease burden.
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Affiliation(s)
- Brittany B Dennis
- Department of Medicine, McMaster University, Hamilton L8S 4L8, ON, Canada
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94304, United States
| | - Leen Naji
- Department of Family Medicine, McMaster University, Hamilton L8P 1H6, ON, Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton L8S 4K1, ON, Canada
| | - Yasmin Jajarmi
- Department of Medicine, McMaster University, Hamilton L8S 4L8, ON, Canada
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94304, United States
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94304, United States
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43
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Torre P, Aglitti A, Masarone M, Persico M. Viral hepatitis: Milestones, unresolved issues, and future goals. World J Gastroenterol 2021; 27:4603-4638. [PMID: 34366625 PMCID: PMC8326259 DOI: 10.3748/wjg.v27.i28.4603] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 04/11/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
In this review the current overall knowledge on hepatitis A, B, C, D, and E will be discussed. These diseases are all characterized by liver inflammation but have significant differences in distribution, transmission routes, and outcomes. Hepatitis B virus and hepatitis C virus are transmitted by exposure to infected blood, and in addition to acute infection, they can cause chronic hepatitis, which in turn can evolve into cirrhosis. It is estimated that more than 300 million people suffer from chronic hepatitis B or C worldwide. Hepatitis D virus, which is also transmitted by blood, only affects hepatitis B virus infected people, and this dual infection results in worse liver-related outcomes. Hepatitis A and E spread via the fecal-oral route, which corresponds mainly to the ingestion of food or water contaminated with infected stools. However, in developed countries hepatitis E is predominantly a zoonosis. Although hepatitis A virus and hepatitis E virus are usually responsible for a self-limiting hepatitis, a serious, rarely fatal illness is also possible, and in immunosuppressed patients, such as organ transplant recipients, hepatitis E virus infection can become chronic. The description of goals achieved, unresolved issues, and the latest research on this topic may make it possible to speculate on future scenarios in the world of viral hepatitis.
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Affiliation(s)
- Pietro Torre
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana,” University of Salerno, Salerno 84081, Italy
| | - Andrea Aglitti
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana,” University of Salerno, Salerno 84081, Italy
| | - Mario Masarone
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana,” University of Salerno, Salerno 84081, Italy
| | - Marcello Persico
- Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana,” University of Salerno, Salerno 84081, Italy
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Higuera-de la Tijera F, Servín-Caamaño A, Servín-Abad L. Progress and challenges in the comprehensive management of chronic viral hepatitis: Key ways to achieve the elimination. World J Gastroenterol 2021; 27:4004-4017. [PMID: 34326610 PMCID: PMC8311524 DOI: 10.3748/wjg.v27.i26.4004] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 03/04/2021] [Accepted: 06/17/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic viral hepatitis is a significant health problem throughout the world, which already represents high annual mortality. By 2040, chronic viral hepatitis due to virus B and virus C and their complications cirrhosis and hepatocellular carcinoma will be more deadly than malaria, vitellogenesis-inhibiting hormone, and tuberculosis altogether. In this review, we analyze the global impact of chronic viral hepatitis with a focus on the most vulnerable groups, the goals set by the World Health Organization for the year 2030, and the key points to achieve them, such as timely access to antiviral treatment of direct-acting antiviral, which represents the key to achieving hepatitis C virus elimination. Likewise, we review the strategies to prevent transmission and achieve control of hepatitis B virus. Finally, we address the impact that the coronavirus disease 2019 pandemic has had on implementing elimination strategies and the advantages of implementing telemedicine programs.
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MESH Headings
- Antiviral Agents/therapeutic use
- COVID-19
- Hepatitis B, Chronic/diagnosis
- Hepatitis B, Chronic/drug therapy
- Hepatitis B, Chronic/epidemiology
- Hepatitis C, Chronic/diagnosis
- Hepatitis C, Chronic/drug therapy
- Hepatitis C, Chronic/epidemiology
- Hepatitis, Viral, Human/diagnosis
- Hepatitis, Viral, Human/drug therapy
- Hepatitis, Viral, Human/epidemiology
- Humans
- Liver Neoplasms/drug therapy
- Liver Neoplasms/epidemiology
- Liver Neoplasms/prevention & control
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Affiliation(s)
| | | | - Luis Servín-Abad
- Department of Gastroenterology, Saint Cloud Hospital, Saint Cloud, MN 56303, United States
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Parlati L, Hollande C, Pol S. Treatment of hepatitis C virus infection. Clin Res Hepatol Gastroenterol 2021; 45:101578. [PMID: 33272891 DOI: 10.1016/j.clinre.2020.11.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Accepted: 11/06/2020] [Indexed: 02/07/2023]
Abstract
Hepatitis C virus infection affects 71 million people worldwide. It is at the origin of a multi-organ disease associating hepatic manifestations, cryoglobulinemic vasculitis and general manifestations linked to chronic inflammation (diabetes, cardio-, reno- or cerebrovascular manifestations, extra-hepatic cancers including non-Hodgkin's lymphoma). The significant morbidity and mortality linked to the hepatitis C virus therefore justify its screening and access to treatments which have increased considerably over the past two decades. Understanding the replicative cycle of the hepatitis C virus has enabled the development of direct HCV-specific antivirals targeting viral proteins (NS3/4A protease, NS5B polymerase and the multifunctional NS5A replication complex). The combination of two to three specific inhibitors often co-formulated in a capsule, without pegylated interferon and most often without ribavirin, allows high antiviral efficacy (more than 97% cure) for a treatment duration of 8-12 weeks with satisfactory tolerance. HCV infection is the only chronic viral infection that can be cured and the hepatic or extrahepatic manifestations are mainly reversible. This underlines the importance of strengthening screening and access to care policies in order to achieve the elimination of viral infection C in the short term, in 2030, as expected from the program of the World Health Organization. If this elimination is possible in some countries (Iceland, France, Germany …), it seems compromised in others where prevention (USA), screening and/or access to care are still insufficient (Sub-Saharan Africa, Russia…).
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Affiliation(s)
- Lucia Parlati
- Département d'Hépatologie, APHP, Hôpital Cochin, Paris, France
| | - Clémence Hollande
- Département d'Hépatologie, APHP, Hôpital Cochin, Paris, France; Université de Paris, Inserm U-1223 et Immunité des Cellules Dendritiques, Institut Pasteur, Paris, France
| | - Stanislas Pol
- Département d'Hépatologie, APHP, Hôpital Cochin, Paris, France; Université de Paris, Inserm U-1223 et Immunité des Cellules Dendritiques, Institut Pasteur, Paris, France.
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46
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Frankova S, Jandova Z, Jinochova G, Kreidlova M, Merta D, Sperl J. Therapy of chronic hepatitis C in people who inject drugs: focus on adherence. Harm Reduct J 2021; 18:69. [PMID: 34193156 PMCID: PMC8247095 DOI: 10.1186/s12954-021-00519-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Accepted: 06/22/2021] [Indexed: 12/31/2022] Open
Abstract
Background Intravenous drug use (IVDU) represents the major factor of HCV transmission, but the treatment uptake among people who inject drugs (PWID) remains low owing to a false presumption of low efficacy. The aim of our study was to assess treatment efficacy in PWID and factors determining adherence to therapy. Methods A total of 278 consecutive patients starting DAA (direct-acting antivirals) therapy were included, divided into two groups: individuals with a history of IVDU, PWID group (N = 101) and the control group (N = 177) without a history of IVDU. Results Sustained virological response 12 weeks after the end of therapy (SVR12) was achieved by 99/101 (98%) and 172/177 (98%) patients in the PWID and control group, respectively; in PWID group, two patients were lost to follow-up, and in the control group, four patients relapsed and one was lost to follow-up. PWID patients postponed appointments significantly more often, 29 (28.7%) in PWID versus 7 (4%) in the control group, p = 0.001. Thirteen of 101 (12.9%) and six of 177 (3.4%) patients in the PWID and in the control group, respectively, missed at least one visit (p < 0.01). However, postponing visits led to a lack of medication in only one PWID. In the PWID group, older age (p < 0.05; OR 1.07, 95% CI 1.00–1.20) and stable housing (p < 0.01; OR 9.70, 95% CI 2.10–56.20) were factors positively contributing to adherence. Contrarily, a stable job was a factor negatively influencing adherence (p < 0.05; OR 0.24, 95% CI 0.06–0.81). In the control group, none of the analyzed social and demographic factors had an impact on adherence to therapy. Conclusions In PWID, treatment efficacy was excellent and was comparable with SVR of the control group. Stable housing and older age contributed to a better adherence to therapy.
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Affiliation(s)
- Sona Frankova
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 14021, Prague, Czech Republic.
| | - Zuzana Jandova
- Psychiatric Hospital Havlickuv Brod, Havlickuv Brod, Czech Republic.,First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Gabriela Jinochova
- Psychiatric Hospital Havlickuv Brod, Havlickuv Brod, Czech Republic.,Addiction Centre Prague, Prague, Czech Republic
| | - Miluse Kreidlova
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Dusan Merta
- Cardiothoracic Anaesthesiology and Intensive Care, Department of Anaesthesiology and Intensive Care Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Jan Sperl
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 14021, Prague, Czech Republic.,First Faculty of Medicine, Charles University, Prague, Czech Republic
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de Salazar A, Dietz J, di Maio VC, Vermehren J, Paolucci S, Müllhaupt B, Coppola N, Cabezas J, Stauber RE, Puoti M, Arenas Ruiz Tapiador JI, Graf C, Aragri M, Jimenez M, Callegaro A, Pascasio Acevedo JM, Macias Rodriguez MA, Rosales Zabal JM, Micheli V, Garcia Del Toro M, Téllez F, García F, Sarrazin C, Ceccherini-Silberstein F, Canbay A, Port K, Cornberg M, Manns M, Reinhardt L, Ellenrieder V, Zizer E, Dikopoulos N, Backhus J, Seufferlein T, Beckebaum S, Hametner S, Schöfl R, Niederau C, Schlee P, Dreck M, Görlitz B, Hinrichsen H, Seegers B, Jung M, Link R, Mauss S, Meister V, Schnaitmann E, Sick C, Simon KG, Schmidt KJ, Andreoni M, Craxì A, Giaccone P, Perno CF, Zazzi M, Bertoli A, Angelico M, Masetti C, Giannelli V, Camillo S, Begini P, De Santis A, Taliani G, Lichtner M, Rossetti B, Caudai C, Cozzolongo R, De Bellis S, Starace M, Minichini C, Gaeta G, Pisaturo MA, Messina V, Dentone C, Bruzzone B, Landonio S, Magni C, Merli M, De Gasperi E, Policlinico GOM, Hasson H, Boeri E, Beretta I, Molteni C, Maffezzini AME, Dorigoni N, Guella L, Götze T, Canbay A, Port K, Cornberg M, Manns M, Reinhardt L, Ellenrieder V, Zizer E, Dikopoulos N, Backhus J, Seufferlein T, et alde Salazar A, Dietz J, di Maio VC, Vermehren J, Paolucci S, Müllhaupt B, Coppola N, Cabezas J, Stauber RE, Puoti M, Arenas Ruiz Tapiador JI, Graf C, Aragri M, Jimenez M, Callegaro A, Pascasio Acevedo JM, Macias Rodriguez MA, Rosales Zabal JM, Micheli V, Garcia Del Toro M, Téllez F, García F, Sarrazin C, Ceccherini-Silberstein F, Canbay A, Port K, Cornberg M, Manns M, Reinhardt L, Ellenrieder V, Zizer E, Dikopoulos N, Backhus J, Seufferlein T, Beckebaum S, Hametner S, Schöfl R, Niederau C, Schlee P, Dreck M, Görlitz B, Hinrichsen H, Seegers B, Jung M, Link R, Mauss S, Meister V, Schnaitmann E, Sick C, Simon KG, Schmidt KJ, Andreoni M, Craxì A, Giaccone P, Perno CF, Zazzi M, Bertoli A, Angelico M, Masetti C, Giannelli V, Camillo S, Begini P, De Santis A, Taliani G, Lichtner M, Rossetti B, Caudai C, Cozzolongo R, De Bellis S, Starace M, Minichini C, Gaeta G, Pisaturo MA, Messina V, Dentone C, Bruzzone B, Landonio S, Magni C, Merli M, De Gasperi E, Policlinico GOM, Hasson H, Boeri E, Beretta I, Molteni C, Maffezzini AME, Dorigoni N, Guella L, Götze T, Canbay A, Port K, Cornberg M, Manns M, Reinhardt L, Ellenrieder V, Zizer E, Dikopoulos N, Backhus J, Seufferlein T, Beckebaum S, Hametner S, Schöfl R, Niederau C, Schlee P, Dreck M, Görlitz B, Hinrichsen H, Seegers B, Jung M, Link R, Mauss S, Meister V, Schnaitmann E, Sick C, Simon KG, Schmidt KJ, Andreoni M, Craxì A, Giaccone P, Perno CF, Zazzi M, Bertoli A, Angelico M, Masetti C, Giannelli V, Camillo S, Begini P, De Santis A, Taliani G, Lichtner M, Rossetti B, Caudai C, Cozzolongo R, De Bellis S, Starace M, Minichini C, Gaeta G, Pisaturo MA, Messina V, Dentone C, Bruzzone B, Landonio S, Magni C, Merli M, De Gasperi E, Policlinico GOM, Hasson H, Boeri E, Beretta I, Molteni C, Maffezzini AME, Dorigoni N, Guella L. Prevalence of resistance-associated substitutions and retreatment of patients failing a glecaprevir/pibrentasvir regimen. J Antimicrob Chemother 2021; 75:3349-3358. [PMID: 32772078 DOI: 10.1093/jac/dkaa304] [Show More Authors] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2020] [Accepted: 06/02/2020] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVES To investigate resistance-associated substitutions (RASs) as well as retreatment efficacies in a large cohort of European patients with failure of glecaprevir/pibrentasvir. METHODS Patients were identified from three European Resistance Reference centres in Spain, Italy and Germany. Sequencing of NS3, NS5A and NS5B was conducted and substitutions associated with resistance to direct antiviral agents were analysed. Clinical and virological parameters were documented retrospectively and retreatment efficacies were evaluated. RESULTS We evaluated 90 glecaprevir/pibrentasvir failures [3a (n = 36), 1a (n = 23), 2a/2c (n = 20), 1b (n = 10) and 4d (n = 1)]. Ten patients were cirrhotic, two had previous exposure to PEG-interferon and seven were coinfected with HIV; 80 had been treated for 8 weeks. Overall, 31 patients (34.4%) failed glecaprevir/pibrentasvir without any NS3 or NS5A RASs, 62.4% (53/85) showed RASs in NS5A, 15.6% (13/83) in NS3 and 10% (9/90) in both NS5A and NS3. Infection with HCV genotypes 1a and 3a was associated with a higher prevalence of NS5A RASs. Patients harbouring two (n = 34) or more (n = 8) RASs in NS5A were frequent. Retreatment was initiated in 56 patients, almost all (n = 52) with sofosbuvir/velpatasvir/voxilaprevir. The overall sustained virological response rate was 97.8% in patients with end-of-follow-up data available. CONCLUSIONS One-third of patients failed glecaprevir/pibrentasvir without resistance. RASs in NS5A were more prevalent than in NS3 and were frequently observed as dual and triple combination patterns, with a high impact on NS5A inhibitor activity, particularly in genotypes 1a and 3a. Retreatment of glecaprevir/pibrentasvir failures with sofosbuvir/velpatasvir/voxilaprevir achieved viral suppression across all genotypes.
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Affiliation(s)
- Adolfo de Salazar
- Clinical Microbiology Unit, University Hospital San Cecilio, Instituto de Investigacion Ibs.Granada. Granada, Spain
| | - Julia Dietz
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt, Germany; German Center for Infection Research (DZIF), External Partner Site, Frankfurt, Germany
| | - Velia Chiara di Maio
- Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Johannes Vermehren
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt, Germany; German Center for Infection Research (DZIF), External Partner Site, Frankfurt, Germany
| | - Stefania Paolucci
- Molecular Virology Unit, Microbiology and Virology Department, IRCCS Policlinic Foundation San Matteo, Pavia, Italy
| | - Beat Müllhaupt
- Swiss Hepato-Pancreato-Biliary Center and Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland
| | - Nicola Coppola
- Department of Mental Health and Public Medicine, Infectious Diseases Unit, University of Campania "L. Vanvitelli", Naples, Italy
| | - Joaquín Cabezas
- Department of Hepatology, Marqués de Valdecilla University Hospital, Santander, Spain
| | - Rudolf E Stauber
- Department of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Massimo Puoti
- Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | | | - Christiana Graf
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt, Germany; German Center for Infection Research (DZIF), External Partner Site, Frankfurt, Germany
| | - Marianna Aragri
- Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Miguel Jimenez
- Hepatology Unit, Hospital Regional de Málaga, Málaga, Spain
| | | | | | | | | | - Valeria Micheli
- Clinical Microbiology, Virology and Bioemergencies, ASST Fatebenefratelli Sacco University Hospital, Milan, Italy
| | | | - Francisco Téllez
- Infectious Diseases Unit, Hospital Puerto Real, Puerto Real, Cádiz, Spain
| | - Federico García
- Clinical Microbiology Unit, University Hospital San Cecilio, Instituto de Investigacion Ibs.Granada. Granada, Spain
| | - Christoph Sarrazin
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt, Germany; German Center for Infection Research (DZIF), External Partner Site, Frankfurt, Germany.,Medizinische Klinik 2, St. Josefs Hospital, Wiesbaden, Germany
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Sarrazin C. Treatment failure with DAA therapy: Importance of resistance. J Hepatol 2021; 74:1472-1482. [PMID: 33716089 DOI: 10.1016/j.jhep.2021.03.004] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 02/24/2021] [Accepted: 03/01/2021] [Indexed: 12/14/2022]
Abstract
Viral resistance is a major reason for virological failure in patients being treated with direct-acting antivirals (DAAs) for chronic HCV infection. However, the importance of viral resistance mainly depends on the DAA regimen and HCV genotype. For first-line therapy with glecaprevir/pibrentasvir (G/P) or velpatasvir/sofosbuvir (VEL/SOF) no general baseline resistance analysis is required because of the high antiviral activity and high barrier to resistance. If available, resistance testing may help to optimise therapy in certain subgroups of patients with HCV genotype 3 and other rare HCV geno/subtypes. Voxilaprevir/velpatasvir/sofosbuvir (VOX/VEL/SOF) is the first choice for the second-line treatment of patients following a previous DAA failure, with rates of viral eradication above 90% irrespective of the presence of resistance-associated substitutions (RASs). However, in resource-limited settings, only first-generation DAAs may be available for second-line therapy. Here, RASs selected during initial antiviral therapy should be considered if testing is available and rescue treatment should include a switch to a regimen with a new DAA class to optimise treatment response. Patients with HCV genotype 3 are overrepresented in the group who experience DAA treatment failure. Limited data are available for third-line therapies, but promising results have been achieved with G/P plus SOF or VOX/VEL/SOF with or without ribavirin for 12 to 24 weeks; these regimens should be administered irrespective of a patient's RAS profile.
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Affiliation(s)
- Christoph Sarrazin
- St. Josefs-Hospital, Beethovenstr. 20, 65189 Wiesbaden, Germany; Goethe-University Hospital, Medizinische Klinik 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
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Kang YW, Baek YH, Lee SW, Park SJ, Yoon JS, Yoon KT, Hong Y, Heo NY, Seo KI, Lee SS, Cho HC, Shin JW. Real-world Effectiveness and Safety of Direct-acting Antiviral Agents in Patients with Chronic Hepatitis C Genotype 2 Infection: Korean Multicenter Study. J Korean Med Sci 2021; 36:e142. [PMID: 34060258 PMCID: PMC8167412 DOI: 10.3346/jkms.2021.36.e142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 04/25/2021] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND The advancement of treatment with direct-acting antiviral (DAA) agents has improved the cure rate of hepatitis C virus (HCV) infection close to 100%. The aim of our study was to assess the real-world effectiveness and safety of DAA regimens for the treatment of patients with chronic HCV genotype 2. METHODS We retrospectively analyzed the clinical data of patients treated with sofosbuvir plus ribavirin (SOF + RBV) or glecaprevir/pibrentasvir (G/P) for chronic HCV genotype 2 infection at seven university hospitals in the Korean southeast region. RESULTS SOF + RBV therapy produced an 89% and 98.3% sustained virologic response 12 week (SVR12) after treatment completion in the full analysis set and per-protocol set, respectively, and the corresponding values for G/P therapy were 89.5% and 99.2%, respectively. The difference between the treatments was probably because 6.2% (59/953) of patients in the SOF + RBV group did not complete the treatment and 9.8% (14/143) in the G/P group did not test HCV RNA after treatment completion. Adverse events (A/Es) were reported in 59.7% (569/953) and 25.9% (37/143) of the SOF + RBV and G/P groups, respectively. In the SOF + RBV group, 12 (1.26%) patients discontinued treatment owing to A/Es, whereas no patients discontinued treatment because of A/Es in the G/P group. CONCLUSION In both treatment groups, SVR was high when treatment was completed. However, there was a high dropout rate in the SOF + RBV group, and the dropout analysis showed that these were patients with liver cirrhosis (LC; 43/285, 15.1%), especially those with decompensated LC (12/32, 37.5%). Therefore, an early initiation of antiviral therapy is recommended for a successful outcome before liver function declines. Furthermore, patients with decompensated LC who are considered candidates for SOF + RBV treatment should be carefully monitored to ensure that their treatment is completed, especially those with low hemoglobin and high alanine transaminase.
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Affiliation(s)
- Yeo Wool Kang
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
| | - Yang Hyun Baek
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea.
| | - Sung Wook Lee
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
| | - Sung Jae Park
- Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Korea
| | - Jun Sik Yoon
- Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Youngmi Hong
- Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Nae Yun Heo
- Department of Internal Medicine, Inje University Haeundae Paik Hospital, Busan, Korea
| | - Kwang Il Seo
- Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Korea
| | - Sang Soo Lee
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea
| | - Hyun Chin Cho
- Department of Internal Medicine, College of Medicine, Gyeongsang National University, Jinju, Korea
| | - Jung Woo Shin
- Department of Internal Medicine, Ulsan University College of Medicine, Ulsan, Korea
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Park YJ, Woo HY, Heo J, Park SG, Hong YM, Yoon KT, Kim DU, Kim GH, Kim HH, Song GA, Cho M. Real-Life Effectiveness and Safety of Glecaprevir/Pibrentasvir for Korean Patients with Chronic Hepatitis C at a Single Institution. Gut Liver 2021; 15:440-450. [PMID: 32839365 PMCID: PMC8129668 DOI: 10.5009/gnl19393] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 06/03/2020] [Accepted: 06/21/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND/AIMS Glecaprevir/pibrentasvir (G/P) is a combination of direct-acting antiviral agents that is an approved treatment for chronic infections by all six hepatitis C virus (HCV) genotypes. However, there are limited data on the effect of G/P in Korean patients in actual real-world settings. We evaluated the real-life effectiveness and safety of G/P at a single institution in Korea. METHODS This retrospective, observational, cohort study used sustained virologic response at 12 weeks after treatment completion (SVR12) as the primary effectiveness endpoint. Safety and tolerability were also determined. RESULTS We examined 267 individuals who received G/P for chronic HCV infections. There were 148 females (55.4%), and the overall median age was 63.0 years (range, 25 to 87 years). Eighty-three patients (31.1%) had HCV genotype-1 and 182 (68.2%) had HCV-2. A total of 212 patients (79.4%) were HCV treatment-naïve, 200 (74.9%) received the 8-week treatment, 13 (4.9%) had received prior treatment for hepatocellular carcinoma, 37 (13.7%) had chronic kidney disease stage 3 or higher, and 10 (3.7%) were receiving dialysis. Intention to treat (ITT) analysis indicated that 256 (95.9%) achieved SVR12. A modified ITT analysis indicated that SVR12 was 97.7% (256/262). Six patients failed therapy because of posttreatment relapse. SVR12 was significantly lower in those who received prior sofosbuvir treatment (p=0.002) and those with detectable HCV RNA at week 4 (p=0.027). Seventy patients (26.2%) experienced one or more adverse events, and most of them were mild. CONCLUSIONS These real-life data indicated that G/P treatment was highly effective and well tolerated, regardless of viral genotype or patient comorbidities.
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Affiliation(s)
- Young Joo Park
- Department of Internal Medicine, College of Medicine, Pusan National University, Busan, Korea
- Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Hyun Young Woo
- Department of Internal Medicine, College of Medicine, Pusan National University, Busan, Korea
- Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Jeong Heo
- Department of Internal Medicine, College of Medicine, Pusan National University, Busan, Korea
- Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Sang Gyu Park
- Department of Internal Medicine, Good Samsun Hospital, Busan, Korea
| | - Young Mi Hong
- Department of Internal Medicine, College of Medicine, Pusan National University, Busan, Korea
- Liver Center, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, College of Medicine, Pusan National University, Busan, Korea
- Liver Center, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Dong Uk Kim
- Department of Internal Medicine, College of Medicine, Pusan National University, Busan, Korea
- Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Gwang Ha Kim
- Department of Internal Medicine, College of Medicine, Pusan National University, Busan, Korea
- Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Hyung Hoi Kim
- Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
- Department of Laboratory Medicine, College of Medicine, Pusan National University, Busan, Korea
| | - Geun Am Song
- Department of Internal Medicine, College of Medicine, Pusan National University, Busan, Korea
- Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Mong Cho
- Department of Internal Medicine, College of Medicine, Pusan National University, Busan, Korea
- Liver Center, Pusan National University Yangsan Hospital, Yangsan, Korea
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