|
1
|
Trelsgård AM, Mulabecirovic A, Leiva RA, Nordaas IK, Mjelle AB, Gilja OH, Havre RF. Multiparametric liver assessment in patients successfully treated for hepatitis C: a 4-year follow-up. Scand J Gastroenterol 2024; 59:1184-1191. [PMID: 39219192 DOI: 10.1080/00365521.2024.2388691] [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: 04/26/2024] [Revised: 06/29/2024] [Accepted: 07/31/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Hepatitis C virus (HCV) is a major cause of chronic liver disease, in which liver stiffness increases. Liver stiffness measurements (LSM) are therefore essential in diagnosing liver diseases and predicting disease development. The study objective was to perform a comprehensive prospective assessment of the liver before, after and 4 years after treatment for HCV, including an assessment of the long-term outcome of fibrosis, steatosis and inflammation. METHODS AND FINDINGS Patients eligible for HCV treatment were included prospectively in 2018 (n = 47). Liver stiffness was measured using transient elastography and 2D shear-wave elastography (SWE). Blood tests, B-mode ultrasound (US) and SWE, were performed before, after (end of treatment [EOT]), 3 months after (EOT3) and 4 years after treatment (4Y). At the final visit, we added attenuation imaging and shear-wave dispersion slope (SWDS) measurements to assess steatosis and inflammation. Three months after treatment, the sustained virologic response rate was 93%. The median liver stiffness for baseline, EOT, EOT3 and 4Y was 8.1, 5.9, 5.6 and 6.3 kPa, respectively. There was a significant reduction in liver stiffness from baseline to EOT, and from EOT to EOT3. After 4 years, the mean attenuation coefficient (AC) was 0.58 dB/cm/MHz, and the mean SWDS value was 14.3 (m/s)/kHz. CONCLUSION The treatment for HCV was highly effective. Measurements of liver stiffness decreased significantly after treatment and remained low after 4 years. AC measurements indicated low levels of liver steatosis. Shear-wave dispersion values indicated inflammation of the liver, but the clinical implication is undetermined and should be explored in larger studies.Clinicaltrials.gov: NCT03434470. ABBREVIATIONS AC: attenuation coefficient; APRI: aspartate aminotransferase to platelet ratio index; ATI: attenuation imaging; cACLD: compensated advanced chronic liver disease; CAP: controlled attenuation parameter; FIB-4: Fibrosis-4 Index for liver fibrosis; HCC: hepatocellular carcinoma; LSM: liver stiffness measurement; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; SWDS: shear-wave dispersion slope; SWE: shear-wave elastography; US: ultrasound.
Collapse
Affiliation(s)
- Audun M Trelsgård
- Department of Medicine, National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Anesa Mulabecirovic
- Department of Medicine, National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway
| | | | - Ingrid K Nordaas
- Department of Medicine, National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Anders B Mjelle
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
- Department of Anaesthesia, Stavanger University Hospital, Stavanger, Norway
| | - Odd Helge Gilja
- Department of Medicine, National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Roald F Havre
- Department of Medicine, National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| |
Collapse
|
|
2
|
Hashmi ZY, Hashmi S, Raza A. Efficacy, safety, and quality of life profile of Genotype-3 Chronic Hepatitis-C Pakistani patients receiving ledipasvir plus sofosbuvir treatment. Pak J Med Sci 2024; 40:1430-1436. [PMID: 39092072 PMCID: PMC11255826 DOI: 10.12669/pjms.40.7.7869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 01/18/2024] [Accepted: 03/26/2024] [Indexed: 08/04/2024] Open
Abstract
Objective This study aimed to assess the overall treatment response of Genotype-3 Chronic HCV Pakistani Patients with or without cirrhosis to Ledipasvir plus Sofosbuvir combination. Method In this observational study, HCV Genotype-3 patients were enrolled from Liver Center, DHQ Hospital, Faisalabad and divided into two groups, i.e., non-cirrhotic and compensated cirrhotic patients. The study spanned for a period of 24 months (November 2019 - November 2021) from the first enrollment to the last follow up. Non-cirrhotic patients received Ledipasvir/Sofosbuvir (LDV/SOF) 90/400mg for 12 weeks and cirrhotic patients received LDV/SOF with Ribavirin (RBV) for 12 weeks and without RBV for 24 weeks. The treatment efficacy in terms of sustained virological response (SVR12) was monitored 12 weeks post-treatment. The safety profile, and health-related quality of life (HRQoL) were monitored from baseline to follow-up visits. Results Two hundred and ninety out of 309 (93.85%) non-cirrhotic and 31 out of 33 (93.94%) compensated cirrhotic patients achieved SVR-12. The safety profile of the non-cirrhotic and compensated cirrhotic patients was comparable throughout the study duration. Fatigue was the most commonly reported adverse event (AE) in non-cirrhotic and compensated cirrhotic patients, followed by headache, nausea, and fever. The HRQoL improved from baseline to follow-up visits among patients of both groups. Conclusion It is concluded that LDV and SOF combination regimen is safe and effective for treating Genotype-3 HCV patients without cirrhosis/compensated cirrhosis, and also improves the patient's HRQoL.
Collapse
Affiliation(s)
- Zahid Yaseen Hashmi
- Dr. Zahid Yaseen Hashmi, FCPS Medicine. Chairman Liver Foundation Trust, Faisalabad, Pakistan
| | - Sandeed Hashmi
- Dr. Sandeed Hashmi, MBBS. Liver Centre Faisalabad, Pakistan
| | - Ali Raza
- Dr. Ali Raza, MBBS. Liver Centre Faisalabad, Pakistan
| |
Collapse
|
|
3
|
Zhang W, Zhang J, Tang S, Liu Y, Du X, Qiu L, Liu M, Yu H, Pan CQ. Efficacy and Safety of Sofosbuvir-based Regimens in Hepatitis C Patients With Decompensated Cirrhosis: A Systematic Review and Meta-analysis. J Clin Transl Hepatol 2023; 11:144-155. [PMID: 36406321 PMCID: PMC9647115 DOI: 10.14218/jcth.2022.00006] [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: 01/04/2022] [Revised: 05/04/2022] [Accepted: 05/13/2022] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND AND AIMS Decompensated cirrhotic patients with hepatitis C (HCV) are often under-represented in clinical trials. We aimed to evaluate pooled data on the efficacy and safety of sofosbuvir (SOF)-based regimens in these patients. METHODS We conducted a systemic review and meta-analysis by searching multiple databases for studies published from October 2010 to October 2020. Outcomes of interest were sustained virologic response (SVR) and safety of SOF-based regimens in decompensated HCV patients. Two reviewers independently performed the study selection and data extraction. RESULTS We included 33 studies that enrolled 5,302 HCV patients. The pooled SVR rate in decompensated patients with SOF-based regimens was 85.1% (95% CI: 82.8-87.3). Patients on SOF/velpatasvir±ribavirin achieved a significantly higher SVR (91.0%, 95% CI: 87.7-93.9) than that of SOF/ledipasvir±ribavirin [(86.3%, 95% CI: 84.6-87.8); p=0.004)], or on SOF/daclatasvir±ribavirin (82.4%, 95% CI: 78.2-86.2%; p<0.001). Adding ribavirin to SOF-based regimens (pooled SVR 84.9%, 95% CI: 81.7-87.9) did not significantly increase the SVR [(83.8% (95% CI: 76.8-89.8%; p=0.76)] in decompensated patients, which was also true in subgroup analyses for each regimen within the same treatment duration. However, adding ribavirin significantly increased the frequency of adverse events from 52.9% (95% CI: 28.0-77.1) to 89.2% (95% CI: 68.1-99.9) and frequency of severe events. The pooled incidence of hepatocellular carcinoma and case-fatality of decompensated patients were 3.1% (95% CI: 1.5-5.0) and 4.6% (95% CI: 3.1-6.3), respectively. The overall heterogeneity was high. There was no publication bias. CONCLUSIONS The analysis found that 12 weeks of SOF/velpatasvir without ribavirin is the preferred therapy, with a significantly higher SVR compared with other SOF-based regimens in decompensated HCV patients.
Collapse
Affiliation(s)
- Wenyan Zhang
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jing Zhang
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Shan Tang
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Yali Liu
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Xiaofei Du
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Lixia Qiu
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Menglu Liu
- Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Haibin Yu
- Beijing Youan Hospital, Capital Medical University, Beijing, China
- Correspondence to: Haibin Yu, The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China. ORCID: https://orcid.org/0000-0002-2123-7790. Tel: +86-13811669802, Fax: +86-10-63056962, E-mail: ; Calvin Q Pan, Tisch Hospital of NYU Langone Health, NYU School of Medicine, NY, USA. ORCID: https://orcid.org/0000-0002-3723-6688. Tel: +1-7188887728, Fax: +1-7183536901, E-mail:
| | - Calvin Q. Pan
- Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Health, NYU Grossman School of Medicine, New York, USA
- Correspondence to: Haibin Yu, The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China. ORCID: https://orcid.org/0000-0002-2123-7790. Tel: +86-13811669802, Fax: +86-10-63056962, E-mail: ; Calvin Q Pan, Tisch Hospital of NYU Langone Health, NYU School of Medicine, NY, USA. ORCID: https://orcid.org/0000-0002-3723-6688. Tel: +1-7188887728, Fax: +1-7183536901, E-mail:
| |
Collapse
|
|
4
|
Rodrigues JPV, Campos GRF, Bittar C, Martinelli ADLC, Campos MSDA, Pereira LRL, Rahal P, Souza FF. Selection dynamics of HCV genotype 3 resistance-associated substitutions under direct-acting antiviral therapy pressure. Braz J Infect Dis 2022; 26:102717. [PMID: 36410397 PMCID: PMC9706524 DOI: 10.1016/j.bjid.2022.102717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 10/07/2022] [Accepted: 10/30/2022] [Indexed: 11/21/2022] Open
Abstract
The chronic hepatitis C (CHC) treatment is currently based on the use of direct-acting antivirals (DAAs), and patients infected with hepatitis C virus genotype 3 (GT3) have emerged as a more difficult-to-cure population. The NS5A inhibitor daclatasvir (DCV) and sofosbuvir (SOF), an NS5B viral polymerase inhibitor, are among the drugs that compose more effective and safer treatment regimens. The virus genetic variability is related to resistance-associated substitutions (RASs) that adversely impact DAAs effectiveness. The aims of this study were to analyze the association of NS5A and NS5B RASs and other clinical factors with DAAs regimens effectiveness in patients with GT3 CHC infection. This was a prospective cohort study performed in a Brazilian university hospital. Individuals older than 18 years with GT3 CHC treated with SOF + DCV ± ribavirin (RBV) or SOF + peginterferon (PEG) + RBV were included. Blood samples were collected at baseline and post-treatment. A total of 121 patients were included. Sustained virological response rates were 87.6% for the SOF + DCV ± RBV group and 80.0% for the SOF + PEG + RBV arm. Cirrhosis, prior treatment with interferon/PEG + RBV, and baseline NS5A RAS were associated with higher risk of treatment failure. The NS5A analysis suggested that A30K, Y93H, and RAS at site 62 were related to failure. Interestingly, a likely compensatory effect was shown between A30K and A62T. Emergence of Y93H was always associated with RAS at position 62. The RASs dynamics comprehension is an important tool to indicate more effective treatment for GT3 patients.
Collapse
Affiliation(s)
- João Paulo Vilela Rodrigues
- Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
| | | | - Cintia Bittar
- Instituto de Biociências, Letras e Ciências Exatas, Universidade Estadual Paulista, São José do Rio Preto, SP, Brasil
| | | | - Marília Silveira de Almeida Campos
- Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
| | - Leonardo Régis Leira Pereira
- Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
| | - Paula Rahal
- Instituto de Biociências, Letras e Ciências Exatas, Universidade Estadual Paulista, São José do Rio Preto, SP, Brasil
| | - Fernanda Fernandes Souza
- Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
| |
Collapse
|
|
5
|
Mita E, Liu LJ, Shing D, Force L, Aoki K, Nakamoto D, Ishizaki A, Konishi H, Mizutani H, Ng LJ. Real-world Safety and Effectiveness of 24-week Sofosbuvir and Ribavirin Treatment in Patients Infected with Rare Chronic Hepatitis C Virus Genotypes 3, 4, 5, or 6 in Japan. Intern Med 2022; 62:1405-1414. [PMID: 36047126 DOI: 10.2169/internalmedicine.0067-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Objectives Real-world evidence on the safety and effectiveness of direct-acting antivirals in patients infected with chronic hepatitis C virus (HCV) genotypes (GTs) 3, 4, 5, or 6 in Japan is limited. This prospective observational study assesses the real-world safety profile and treatment effectiveness among patients prescribed sofosbuvir with ribavirin (SOF+RBV) for HCV GT3-6 infection in Japan. Methods Adults receiving 24-week SOF+RBV treatment for HCV GT3-6 infection were prospectively enrolled and observed through 24 weeks post-treatment for treatment-emergent adverse events (AEs) considered related to SOF and/or RBV by treating physicians and for a sustained virologic response at 12 and 24 weeks post-treatment (SVR12, SVR24). Incidence rates of related AEs and serious AEs (SAEs) were calculated. Proportions of patients experiencing related AEs/SAEs and those achieving SVR12 and SVR24 were assessed overall and by baseline characteristics, including treatment experience and cirrhosis status. Results Among the 50 patients included in the safety analysis, 92% had GT3 infection. The incidence rates of related AEs and SAEs were low overall (1.52 and 0.25 per 100 person-weeks, respectively), with 6.0% and 14.0% patients experiencing AEs related to SOF or RBV, respectively. There were no marked differences in the occurrence of related AEs/SAEs by patient baseline characteristics. SVR12 and SVR24 were achieved in 83.7% (41/49) and 82.2% (37/45) of patients, respectively. Lower effectiveness was observed among treatment-experienced patients and patients with cirrhosis at baseline. Conclusions This study demonstrated that SOF+RBV treatment for HCV GT3-6 infection was safe, effective, and an important treatment option for this difficult-to-treat patient population in Japan.
Collapse
Affiliation(s)
- Eiji Mita
- National Hospital Organization Osaka National Hospital, Japan
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
6
|
Majid A, Khan S, Siraj S, Haleem S, ul Haq N, Ullah R, Ali EA, Mustafa A, Hussain H, Sohaib M. Emergence of resistance against direct acting antivirals in chronic HCV patients: A real-world study. Saudi J Biol Sci 2022; 29:2613-2619. [PMID: 35531150 PMCID: PMC9072881 DOI: 10.1016/j.sjbs.2021.12.044] [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: 10/26/2021] [Revised: 12/02/2021] [Accepted: 12/19/2021] [Indexed: 01/09/2023] Open
Abstract
Interferon/Ribavirin therapy has been replaced by Direct Acting Antivirals (DAAs) due to emergence of Resistance Associated Variants (RAVs) and decrease Sustain Virologic Response (SVR). Current study investigated treatment response of Sofosbuvir and Ribavirin in chronic HCV patients. Total 256 HCV patients with genotype 1a, 2 and 3a received sofosbuvir/ribavirin according to international standards. HCV RNA presence in serum was used as marker for end treatment response (ETR) and sustain virologic response after 24 weeks of treatment (SVR24) in each case. Response to treatment with SOF + RBV was found statistically significant among different HCV genotypes (GT) as out of 47 HCV GT1 patients 42(89.36%) resulted into good ETR but 4(9.52%) of these relapsed and 5(10.63%) led into virologic failure. 5(100%) HCV GT2 patients resulted into SVR24 whereas, out of 204 HCV GT3 patients 194(95.69%) achieved good ETR however, 8(4.12%) of these relapsed and 10(4.90%) resulted in to virologic failure. Efficacy of therapy was found non-significant in treatment naïve and treatment experienced patients as in this study out of 145 treatment naïve patients 139(95.86%) achieved good ETR where 4(2.87%) relapsed while 6(4.13%) led into virologic break through on the other hand among 111 treatment experienced patients 102(91.89%) resulted into good ETR but 8(7.84%) relapsed whereas 9(8.10%) lead into virologic failure. Current study also propose that various liver and spleen complications/liver cirrhosis are related to response of HCV patients to SOF + RBV therapy whereas, variables like old age, gender is not compromising treatment response to DAAs therapy. Various mild side effects encountered by patients during treatment were fatigue, insomnia, headache, nausea, burning body, diarrhea, cough. Overall, this study reported 89.45% efficacy of SOF + RBV regime in chronic HCV Pakistani patients. Current study suggests hunting for possible reasons of resistance so that SOF + RBV therapy may not share the same fortune as previous therapies in near future.
Collapse
Affiliation(s)
- Abdul Majid
- Department of Zoology, Kohat University of Science and Technology, Kohat, Pakistan
| | | | - Sami Siraj
- Institute of Basic Medical Sciences, Khyber Medical University, Pakistan
| | - Sumbal Haleem
- Department of Zoology, Kohat University of Science and Technology, Kohat, Pakistan
| | - Najib ul Haq
- Peshawar Medical College, Riphah International University, Pakistan
| | - Riaz Ullah
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Essam A. Ali
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Adeela Mustafa
- Community Medicine Department, Khyber Medical College Peshawar, Pakistan
| | - Hidayat Hussain
- Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120 Halle (Salle), Germany
| | - Muhammad Sohaib
- Department of Soil Science, College of Food and Agricultural Sciences, King Saud University, 12 Riyadh 11451, Saudi Arabia
| |
Collapse
|
|
7
|
Meshram RJ, Kathwate GH, Gacche RN. Progress, evolving therapeutic/diagnostic approaches, and challenges in the management of hepatitis C virus infections. Arch Virol 2022; 167:717-736. [PMID: 35089390 PMCID: PMC8795940 DOI: 10.1007/s00705-022-05375-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2021] [Accepted: 12/02/2021] [Indexed: 12/11/2022]
Abstract
Hepatitis C virus (HCV) infections are emerging as one of the foremost challenges in healthcare owing to its chronicity and the virus's quasispecies nature. Worldwide, over 170 million people are chronically infected with HCV, with an annual mortality of over 500,000 people across the world. The emerging pathophysiological evidence links HCV infections to a risk of developing liver diseases such as cirrhosis and hepatocellular carcinoma. Despite the great strides that have been made towards understanding the pathophysiology of disease progression, the tailored treatments of HCV infection remain to be established. The present review provides an update of the literature pertaining to evolving therapeutic approaches and prophylactic measures for the effective management of HCV infections. An extensive discussion of established and experimental immune prophylactic measures also sheds light on current developments in the design of vaccination strategies against HCV infection. We have also attempted to address the application of nanotechnology in formulating effective therapeutic interventions against HCV. Pointing out the limitations of the existing diagnostic methods and therapeutic approaches against HCV might inspire the design and development of novel, efficient, reliable, and cost-effective diagnostic technologies as well as novel therapeutic and immune prophylactic interventions for the effective management of HCV.
Collapse
Affiliation(s)
| | | | - Rajesh Nivarti Gacche
- Department of Biotechnology, Savitribai Phule Pune University, Pune, MS, 411007, India.
| |
Collapse
|
|
8
|
Zhuang L, Li J, Zhang Y, Ji S, Li Y, Zhao Y, Li B, Li W, Quan M, Duan Y, Zhao H, Cheng D, Wang X, Ou W, Xing H. Real-World Effectiveness of Direct-Acting Antiviral Regimens against Hepatitis C Virus (HCV) Genotype 3 Infection: A Systematic Review and Meta-Analysis. Ann Hepatol 2022; 23:100268. [PMID: 33059055 DOI: 10.1016/j.aohep.2020.09.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 09/16/2020] [Accepted: 09/21/2020] [Indexed: 02/04/2023]
Abstract
Patients with hepatitis C virus (HCV) genotype 3 (GT3) infection are resistant to direct-acting antiviral (DAA) treatments. This study aimed to analyze the effectiveness of sofosbuvir (SOF)+daclatasvir (DCV) ± ribavirin (RBV); SOF+velpatasvir (VEL)±RBV; SOF+VEL+voxilaprevir (VOX); and glecaprevir (GLE)+pibrentasvir (PIB) in the treatment of HCV GT3-infected patients in real-world studies. Articles were identified by searching the PubMed, EMBASE, and Cochrane Library databases from January 1, 2016 to September 10, 2019. The meta-analysis was conducted to determine the sustained virologic response (SVR) rate, using R 3.6.2 software. Thirty-four studies, conducted on a total of 7328 patients from 22 countries, met the inclusion criteria. The pooled SVR rate after 12/24 weeks of treatment was 92.07% (95% CI: 90.39-93.61%) for the evaluated regimens. Also, the SVR rate was 91.17% (95% CI: 89.23-92.94%) in patients treated with SOF+DCV±RBV; 95.08% (95% CI: 90.88-98.13%) in patients treated with SOF+VEL±RBV; 84.97% (95% CI: 73.32-93.91%) in patients treated with SOF+VEL+VOX; and 98.54% (95% CI: 96.40-99.82%) in patients treated with GLE+PIB. The pooled SVR rate of the four regimens was 95.24% (95% CI: 93.50-96.75%) in non-cirrhotic patients and 89.39% (95% CI: 86.07-92.33%) in cirrhotic patients. The pooled SVR rate was 94.41% (95% CI: 92.02-96.42%) in treatment-naive patients and 87.98% (95% CI: 84.31-91.25%) in treatment-experienced patients. The SVR rate of GLE+PIB was higher than other regimens. SOF+VEL+VOX can be used as a treatment regimen following DAA treatment failure.
Collapse
Affiliation(s)
- Liwei Zhuang
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China; Peking University Ditan Teaching Hospital, Beijing, China
| | - Junnan Li
- Department of Science and Education, Beijing Ditan Hospital, Capital Medical University, Beijing, China; Peking University Ditan Teaching Hospital, Beijing, China
| | - Yu Zhang
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Shibo Ji
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yue Li
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yingying Zhao
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ben Li
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wei Li
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Min Quan
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ying Duan
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hong Zhao
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Danying Cheng
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaomei Wang
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China; Peking University Ditan Teaching Hospital, Beijing, China
| | - Weini Ou
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China; Peking University Ditan Teaching Hospital, Beijing, China
| | - Huichun Xing
- Center of Liver Disease Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China; Peking University Ditan Teaching Hospital, Beijing, China.
| |
Collapse
|
|
9
|
Raza MN, Sughra K, Zeeshan N, Anwar MZ, Shahzad MA, Rashid U, Afroz A, Munir H. Recurrence of hepatitis C virus after treatment with pegylated interferon and direct acting antivirals in Punjab Pakistan. BRAZ J BIOL 2021; 83:e252610. [PMID: 34909837 DOI: 10.1590/1519-6984.252610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 07/01/2021] [Indexed: 11/22/2022] Open
Abstract
Although increased response rates concomitant in hepatitis C virus but relapse after treatment is threatened. Therefore, it is terrible requirement to evaluate the response of Pegylated interferon and direct acting antivirals in Punjab Pakistan. The study was conducted to find the rate of recurrence of HCV infection after treatment with Pegylated Interferon and Direct Acting Antivirals in Punjab Pakistan. This study was conducted at Department of Pathology, Nawaz Sharif Medical College Gujrat, while treatment effects monitored in different Government and Private Hospitals of Punjab, Pakistan. Total 973 patients who administered the recommended dose and divided in two groups (i) Interferon based therapy (ii) direct acting antivirals (DAAs).Other parameters like ALT and viral load studied. The rate of recurrence was higher in female infected with genotype 2b and in male with mixed genotype 3a/2b after six month of antiviral therapy. Genotype 3a showed significant response to therapy after three month. 32 among 374 (8.5%) were positive after 24 weeks of treatment with interferon, 29 (7.7%) patients have same genotype while 3 patients were re-infected with different HCV strains. With DAAs, only 27 (4.8%) patients were positive among 558 after 2 weeks and one patient re-infected with different genotype. Early and sustained virological response noted in DAAs. ALT and viral load decreased faster with DAAs that not achieved after 4 weeks with pegylated interferon. Sustained virological response appears in DAAs and recurrence rate is high in interferon therapy compared to DAAs. Therefore, reinfection has implications for correct treatment efficiency and to select strategies for retreatment cases.
Collapse
Affiliation(s)
- M N Raza
- University of Gujrat, Department of Biochemistry and Biotechnology, Gujrat, Punjab, Pakistan
| | - K Sughra
- University of Gujrat, Department of Biochemistry and Biotechnology, Gujrat, Punjab, Pakistan
| | - N Zeeshan
- University of Gujrat, Department of Biochemistry and Biotechnology, Gujrat, Punjab, Pakistan
| | - M Z Anwar
- Department of Biochemistry, Combined Military Hospital, Kharian Medical College, Kharian, Punjab, Pakistan
| | - M A Shahzad
- Department of Anesthesia, Major Shabeer Shareef THQ Hospital, Kunjah, Punjab, Pakistan
| | - U Rashid
- University of Gujrat, Department of Biochemistry and Biotechnology, Gujrat, Punjab, Pakistan
| | - A Afroz
- University of Gujrat, Department of Biochemistry and Biotechnology, Gujrat, Punjab, Pakistan
| | - H Munir
- University of Gujrat, Department of Biochemistry and Biotechnology, Gujrat, Punjab, Pakistan
| |
Collapse
|
|
10
|
Andrieux-Meyer I, Tan SS, Thanprasertsuk S, Salvadori N, Menétrey C, Simon F, Cressey TR, Said HRHM, Hassan MRA, Omar H, Tee HP, Chan WK, Kumar S, Thongsawat S, Thetket K, Avihingsanon A, Khemnark S, Yerly S, Ngo-Giang-Huong N, Siva S, Swanson A, Goyal V, Bompart F, Pécoul B, Murad S. Efficacy and safety of ravidasvir plus sofosbuvir in patients with chronic hepatitis C infection without cirrhosis or with compensated cirrhosis (STORM-C-1): interim analysis of a two-stage, open-label, multicentre, single arm, phase 2/3 trial. Lancet Gastroenterol Hepatol 2021; 6:448-458. [PMID: 33865507 PMCID: PMC9767645 DOI: 10.1016/s2468-1253(21)00031-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 01/22/2021] [Accepted: 01/22/2021] [Indexed: 12/30/2022]
Abstract
BACKGROUND In low-income and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, and sofosbuvir has shown efficacy and safety in patients with chronic HCV genotype 4 infection. STORM-C-1 trial aimed to assess the efficacy and safety of ravidasvir plus sofosbuvir in a diverse population of adults chronically infected with HCV. METHODS STORM-C-1 is a two-stage, open-label, phase 2/3 single-arm clinical trial in six public academic and non-academic centres in Malaysia and four public academic and non-academic centres in Thailand. Patients with HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-3) aged 18-69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for patients without cirrhosis and for 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA <12 IU/mL in Thailand and HCV RNA <15 IU/mL in Malaysia at 12 weeks after the end of treatment). This trial is registered with ClinicalTrials.gov, number NCT02961426, and the National Medical Research Register of Malaysia, NMRR-16-747-29183. FINDINGS Between Sept 14, 2016, and June 5, 2017, 301 patients were enrolled in stage one of STORM-C-1. 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection. 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment. The most common treatment-emergent adverse events were pyrexia (35 [12%]), cough (26 [9%]), upper respiratory tract infection (23 [8%]), and headache (20 [7%]). There were no deaths or treatment discontinuations due to serious adverse events related to study drugs. Of the 300 patients included in the full analysis set, 291 (97%; 95% CI 94-99) had SVR12. Of note, SVR12 was reported in 78 (96%) of 81 patients with cirrhosis and 153 (97%) of 158 patients with genotype 3 infection, including 51 (96%) of 53 patients with cirrhosis. There was no difference in SVR12 rates by HIV co-infection or previous interferon treatment. INTERPRETATION In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality. FUNDING National Science and Technology Development Agency, Thailand; Department of Disease Control, Ministry of Public Health, Thailand; Ministry of Health, Malaysia; UK Aid; Médecins Sans Frontières (MSF); MSF Transformational Investment Capacity; FIND; Pharmaniaga; Starr International Foundation; Foundation for Art, Research, Partnership and Education; and the Swiss Agency for Development and Cooperation.
Collapse
Affiliation(s)
| | - Soek-Siam Tan
- Department of Hepatology, Selayang Hospital, Batu Caves, Malaysia
| | | | - Nicolas Salvadori
- Public Health Promotion Research and Training-Institut de Recherche pour le Développement, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
| | | | - François Simon
- Drugs for Neglected Diseases initiative, Geneva, Switzerland
| | - Tim R Cressey
- Public Health Promotion Research and Training-Institut de Recherche pour le Développement, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; Department of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, UK
| | | | | | - Haniza Omar
- Department of Hepatology, Selayang Hospital, Batu Caves, Malaysia
| | - Hoi-Poh Tee
- Gastroenterology Unit, Medical Department, Hospital Tengku Ampuan Afzan, Kuantan, Malaysia
| | - Wah Kheong Chan
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Suresh Kumar
- Infectious Disease Unit, Medical Department, Hospital Sungai Buloh, Selangor, Malaysia
| | - Satawat Thongsawat
- Department of Internal Medicine, Chiang Mai University, Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand
| | - Kanawee Thetket
- Internal Medicine unit, Medical Department, Nakornping Hospital, Chiang Mai, Thailand
| | - Anchalee Avihingsanon
- HIV-Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand; Tuberculosis Research Unit, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Suparat Khemnark
- Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand
| | - Sabine Yerly
- Laboratory of Virology, Geneva University Hospitals, Geneva, Switzerland
| | - Nicole Ngo-Giang-Huong
- Public Health Promotion Research and Training-Institut de Recherche pour le Développement, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; Laboratory of Virology, Program for HIV Prevention and Treatment L'Institut de Recherche pour le Développement, Chiang Mai, Thailand
| | - Sasikala Siva
- Drugs for Neglected Diseases initiative, Kuala Lumpur, Malaysia
| | | | - Vishal Goyal
- Drugs for Neglected Diseases initiative, New York, NY, USA
| | | | - Bernard Pécoul
- Drugs for Neglected Diseases initiative, Geneva, Switzerland
| | | |
Collapse
|
|
11
|
Janczewska E, Kołek MF, Lorenc B, Klapaczyński J, Tudrujek-Zdunek M, Sitko M, Mazur W, Zarębska-Michaluk D, Buczyńska I, Dybowska D, Czauż-Andrzejuk A, Berak H, Krygier R, Jaroszewicz J, Citko J, Piekarska A, Dobracka B, Socha Ł, Deroń Z, Laurans Ł, Białkowska-Warzecha J, Tronina O, Adamek B, Tomasiewicz K, Simon K, Pawłowska M, Halota W, Flisiak R. Factors influencing the failure of interferon-free therapy for chronic hepatitis C: Data from the Polish EpiTer-2 cohort study. World J Gastroenterol 2021; 27:2177-2192. [PMID: 34025072 PMCID: PMC8117732 DOI: 10.3748/wjg.v27.i18.2177] [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: 01/26/2021] [Revised: 03/13/2021] [Accepted: 04/21/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C, making it highly effective and safe for patients. However, few researchers have analyzed the factors causing therapy failure in some patients.
AIM To analyze factors influencing the failure of direct antiviral drugs in the large, multicenter EpiTer-2 cohort in a real-world setting.
METHODS The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from 2016-2020. Data collected from the online EpiTer-2 database included the following: hepatitis C virus (HCV) genotype, stage of fibrosis, hematology and liver function parameters, Child-Turcotte-Pugh and Model for End-stage Liver Disease scores, prior antiviral therapy, concomitant diseases, and drugs used in relation to hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV) coinfections. Adverse events observed during the treatment and follow-up period were reported. Both standard and machine learning methods were used for statistical analysis.
RESULTS During analysis, 12614 patients with chronic hepatitis C were registered, of which 11938 (mean age: 52 years) had available sustained virologic response (SVR) data [11629 (97%) achieved SVR and 309 (3%) did not]. Most patients (78.1%) were infected with HCV genotype 1b. Liver cirrhosis was diagnosed in 2974 patients, while advanced fibrosis (F3) was diagnosed in 1717 patients. We included patients with features of hepatic failure at baseline [ascites in 142 (1.2%) and encephalopathy in 68 (0.6%) patients]. The most important host factors negatively influencing treatment efficacy were liver cirrhosis, clinical and laboratory features of liver failure, history of hepatocellular carcinoma, and higher body mass index. Among viral factors, genotype 3 and viral load also exerted an influence on treatment efficacy. Classical statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex, which was not confirmed by the multivariate analysis using the machine learning algorithm (random forest). Coinfection with HBV (including patients with on-treatment reactivation of HBV infection) or HIV, extrahepatic manifestations, and renal failure did not significantly affect the treatment efficacy.
CONCLUSION In patients with advanced liver disease, individualized therapy (testing for resistance-associated variants and response-guided treatment) should be considered to maximize the chance of achieving SVR.
Collapse
Affiliation(s)
- Ewa Janczewska
- Department of Basic Medical Sciences, The School of Health Sciences in Bytom, Medical University of Silesia, Bytom 41-902, Poland
| | - Mateusz Franciszek Kołek
- Department of Animal Physiology, Faculty of Biology, University of Warsaw, Warszawa 02-096, Poland
| | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Medical University Gdańsk, Gdańsk 80-214, Poland
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, Warszawa 02-507, Poland
| | | | - Marek Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University, Kraków 30-688, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Medical University of Silesia in Katowice, Chorzów 41-500, Poland
| | | | - Iwona Buczyńska
- Department of Infectious Diseases and Hepatology, Medical University Wrocław, Wrocław 51-149, Poland
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Ludwik Rydygier Collegium Medicum in Bydgoszcz Faculty of Medicine Nicolaus Copernicus University in Toruń, Bydgoszcz 85-030, Poland
| | - Agnieszka Czauż-Andrzejuk
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-540, Poland
| | - Hanna Berak
- One-Day Department, Hospital for Infectious Diseases in Warsaw, Warszawa 01-201, Poland
| | - Rafał Krygier
- Outpatient Clinic, State University of Applied Sciences in Konin, Konin 62-510, Poland
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia in Katowice, Bytom 41-902, Poland
| | - Jolanta Citko
- Department of Medical Practice of Infections, Regional Hospital, Olsztyn 10-561, Poland
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź, Łódź 90-419, Poland
| | | | - Łukasz Socha
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, Szczecin 71-455, Poland
| | - Zbigniew Deroń
- Ward of Infectious Diseases and Hepatology, Biegański Regional Specialist Hospital, Łódź 91-347, Poland
| | - Łukasz Laurans
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, Szczecin 71-455, Poland
- Infectious and Liver Diseases Clinic, Multidisciplinary Regional Hospital, Gorzów Wielkopolski 66-400, Poland
| | | | - Olga Tronina
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warszawa 02-091, Poland
| | - Brygida Adamek
- Department of Basic Medical Sciences, The School of Health Sciences in Bytom, Medical University of Silesia, Bytom 41-902, Poland
| | - Krzysztof Tomasiewicz
- Department of Infectious Diseases, Medical University of Lublin, Lublin 20-081, Poland
| | - Krzysztof Simon
- Department of Infectious Diseases and Hepatology, Medical University Wrocław, Wrocław 51-149, Poland
| | - Malgorzata Pawłowska
- Department of Paediatric Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Toruń, Bydgoszcz 85-030, Poland
| | - Waldemar Halota
- Department of Infectious Diseases and Hepatology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Faculty of Medicine, Nicolaus Copernicus University in Toruń, Bydgoszcz 85-030, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-540, Poland
| |
Collapse
|
|
12
|
Gupta E, Agarwal R, Rastogi A, Rani N, Jindal A. Naturally Occurring Resistance Associated Substitutions in Non-Cirrhotic, Treatment Naive HCV-HIV Co-Infected Patients Does Not Affect the Treatment Response for Anti-HCV Antiviral Therapy. Infect Drug Resist 2021; 14:1381-1387. [PMID: 33880042 PMCID: PMC8052117 DOI: 10.2147/idr.s301032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 03/13/2021] [Indexed: 12/27/2022] Open
Abstract
Purpose Limited literature on the prevalence of baseline resistance associated substitutions (BL-RAS) among HCV–HIV co-infected patients and their association with treatment outcomes is available especially from India. Hence, the present study aimed to study naturally occurring RAS among non-cirrhotic HCV–HIV co-infected patients and their impact on the response to anti-HCV therapy. Patients and Methods In this retrospective study, archived blood samples of 80 HCV–HIV co-infected patients, before anti-HCV therapy initiation, were tested for substitutions at the drug acting sites (NS5a and NS5b) in the HCV genome by direct PCR sequencing. Results BL-RAS were seen in 19 (23.7%) patients. As well as BL-RAS, all patients were given sofosbuvir (SOF) 400 mg+ daclatasvir (DCV) 60 mg for 12 weeks. Overall, sustained virological response (SVR) was achieved in 63 (78.8%) patients, in 13 with BL-RAS and in 50 without BL-RAS. All the SVR failure cases (n=17) were retreated with SOF (400 mg) +DCV (60 mg)+ ribavirin (RBV) for 24 weeks. SVR was eventually attained in 14 (82.3%) patients, in 4/6 (66.6%) with BL-RAS and in 10/11 (91%) without BL-RAS. On univariate analysis, age more than 30 years (OR: 11.6; 95% CI: 3.0–45.5, p-value<0.001) and female gender (OR: 8.6; 95% CI: 1.1−69, p-value <0.009) were found to be significant factors associated with the attainment of SVR. Conclusion BL-RAS are common in HCV–HIV co-infected patients. The existence of BL-RAS, however, did not affect the attainment of SVR among non-cirrhotic, treatment naive HCV–HIV co-infected patients.
Collapse
Affiliation(s)
- Ekta Gupta
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Reshu Agarwal
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Aayushi Rastogi
- Department of Epidemiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Nitiksha Rani
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| |
Collapse
|
|
13
|
Zarębska-Michaluk D. Genotype 3-hepatitis C virus’ last line of defense. World J Gastroenterol 2021; 27:1006-1021. [PMID: 33776369 PMCID: PMC7985731 DOI: 10.3748/wjg.v27.i11.1006] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 01/24/2021] [Accepted: 03/01/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic infection with hepatitis C virus (HCV) is one of the leading causes of liver disease globally, affecting approximately 71 million people. The majority of them are infected with genotype (GT) 1 but infections with GT3 are second in frequency. For many years, GT3 was considered to be less pathogenic compared to other GTs in the HCV family due to its favorable response to interferon (IFN)-based regimen. However, the growing evidence of a higher rate of steatosis, more rapid progression of liver fibrosis, and lower efficacy of antiviral treatment compared to infection with other HCV GTs has changed this conviction. This review presents the specifics of the course of GT3 infection and the development of therapeutic options for GT3-infected patients in the era of direct-acting antivirals (DAA). The way from a standard of care therapy with pegylated IFN-alpha (pegIFNα) and ribavirin (RBV) through a triple combination of pegIFNα + RBV and DAA to the highly potent IFN-free pangenotypic DAA regimens is discussed along with some treatment options which appeared to be dead ends. Although the implementation of highly effective pangenotypic regimens is the most recent stage of revolution in the treatment of GT3 infection, there is still room for improvement, especially in patients with liver cirrhosis and those who fail to respond to DAA therapies, particularly those containing inhibitors of HCV nonstructural protein 5A.
Collapse
Affiliation(s)
- Dorota Zarębska-Michaluk
- Department of Infectious Diseases, Jan Kochanowski University, Kielce 25-369, Świętokrzyskie, Poland
| |
Collapse
|
|
14
|
Fahnøe U, Pedersen MS, Sølund C, Ernst A, Krarup HB, Røge BT, Christensen PB, Laursen AL, Gerstoft J, Thielsen P, Madsen LG, Pedersen AG, Schønning K, Weis N, Bukh J. Global evolutionary analysis of chronic hepatitis C patients revealed significant effect of baseline viral resistance, including novel non-target sites, for DAA-based treatment and retreatment outcome. J Viral Hepat 2021; 28:302-316. [PMID: 33131178 DOI: 10.1111/jvh.13430] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 09/20/2020] [Accepted: 09/28/2020] [Indexed: 12/11/2022]
Abstract
Direct-acting antivirals (DAAs) have proven highly effective against chronic hepatitis C virus (HCV) infection. However, some patients experience treatment failure, associated with resistance-associated substitutions (RASs). Our aim was to investigate the complete viral coding sequence in hepatitis C patients treated with DAAs to identify RASs and the effects of treatment on the viral population. We selected 22 HCV patients with sustained virologic response (SVR) to match 21 treatment-failure patients in relation to HCV genotype, DAA regimen, liver cirrhosis and previous treatment experience. Viral-titre data were compared between the two patient groups, and HCV full-length open reading frame deep-sequencing was performed. The proportion of HCV NS5A-RASs at baseline was higher in treatment-failure (82%) than matched SVR patients (25%) (p = .0063). Also, treatment failure was associated with slower declines in viraemia titres. Viral population diversity did not differ at baseline between SVR and treatment-failure patients, but failure was associated with decreased diversity probably caused by selection for RAS. The NS5B-substitution 150V was associated with sofosbuvir treatment failure in genotype 3a. Further, mutations identified in NS2, NS3-helicase and NS5A-domain-III were associated with DAA treatment failure in genotype 1a patients. Six retreated HCV patients (35%) experienced 2nd treatment failure; RASs were present in 67% compared to 11% with SVR. In conclusion, baseline RASs to NS5A inhibitors, but not virus population diversity, and lower viral titre decline predicted HCV treatment failure. Mutations outside of the DAA targets can be associated with DAA treatment failure. Successful DAA retreatment in patients with treatment failure was hampered by previously selected RASs.
Collapse
Affiliation(s)
- Ulrik Fahnøe
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.,Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Martin S Pedersen
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.,Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Department of Clinical Microbiology, Copenhagen University Hospital, Hvidovre, Denmark.,Department of Science and Environment, Roskilde University, Roskilde, Denmark
| | - Christina Sølund
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.,Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark
| | - Anja Ernst
- Department of Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark
| | - Henrik B Krarup
- Department of Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark.,Department of Medical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
| | - Birgit T Røge
- Department of Medicine, Lillebaelt Hospital, Kolding, Denmark
| | - Peer B Christensen
- Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.,Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
| | - Alex L Laursen
- Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark
| | - Jan Gerstoft
- Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Peter Thielsen
- Department of Gastroenterology, Copenhagen University Hospital, Herlev, Denmark
| | - Lone G Madsen
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Department of Medical Gastroenterology, Zealand University Hospital, Køge, Denmark
| | - Anders G Pedersen
- Department of Health Technology, Section for Bioinformatics, Technical University of Denmark, Lyngby, Denmark
| | - Kristian Schønning
- Department of Clinical Microbiology, Copenhagen University Hospital, Hvidovre, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Denmark
| | - Nina Weis
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jens Bukh
- Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.,Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark
| |
Collapse
|
|
15
|
Aas CF, Vold JH, Skurtveit S, Odsbu I, Chalabianloo F, Økland JM, Leiva RAM, Vickerman P, Johansson KA, Fadnes LT. On the path towards universal coverage of hepatitis C treatment among people receiving opioid agonist therapy (OAT) in Norway: a prospective cohort study from 2013 to 2017. BMJ Open 2020; 10:e036355. [PMID: 32847908 PMCID: PMC7451452 DOI: 10.1136/bmjopen-2019-036355] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVES We aimed to calculate cumulative hepatitis C virus (HCV) treatment coverage among individuals enrolled in opioid agonist therapy (OAT) in Norway between 2013 and 2017 and to document the treatment transition to direct-acting antiviral (DAA) agents. Moreover, we aimed to describe adherence to DAAs in the same cohort. DESIGN Prospective cohort, registry data. SETTING Specialist healthcare service (secondary) PARTICIPANTS AND OUTCOMES: This observational study was based on data from The Norwegian Prescription Database. We studied dispensed OAT and HCV treatment annually to calculate the cumulative frequency, and employed secondary sources to calculate prevalence, incidence and HCV treatment coverage from 2013 to 2017, among the OAT population. Factors associated with adherence to DAAs were identified a priori and subject to logistic regression. RESULTS 10 371 individuals were identified with dispensed OAT, 1475 individuals of these were identified with dispensed HCV treatment. Annual HCV treatment coverage increased from 3.5% (95% CI: 3.2 to 4.4) in 2013 to 17% (95% CI: 17 to 20) in 2017, giving a cumulative HCV coverage among OAT patients in Norway of 38.5%. A complete shift to interferon-free treatment regimens occurred, where DAAs accounting for 32% of HCV treatments in 2013 and 99% in 2017. About two-thirds of OAT patients were considered adherent to their DAA regimens across all genotypes. High level of OAT continuity was associated with improved adherence to DAAs (adjusted OR 1.4, 95% CI: 1 to 2, p=0.035). CONCLUSIONS A large increase in HCV treatment coverage attributed by a complete shift to interferon-free regimens among the Norwegian OAT population has been demonstrated. However, treatment coverage is inadmissibly too low and a further substantial scale-up in HCV treatment is required to reach the universal targets of controlling and eliminating the HCV endemic.
Collapse
Affiliation(s)
- Christer Frode Aas
- Department of Addiction Medicine, Helse Bergen HF, Bergen, Norway
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
| | - Jørn Henrik Vold
- Department of Addiction Medicine, Helse Bergen HF, Bergen, Norway
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
| | - Svetlana Skurtveit
- Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway
- Norwegian Centre for Addiction Research, University of Oslo, Oslo, Norway
| | - Ingvild Odsbu
- Department of Medicine, Karolinska Institute, Stockholm, Sweden
| | - Fatemeh Chalabianloo
- Department of Addiction Medicine, Helse Bergen HF, Bergen, Norway
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
| | - Jan Magnus Økland
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
| | | | - Peter Vickerman
- London School of Hygiene and Tropical Medicine, London, UK
- School of Social and Community Medicine, University of Bristol, Bristol, UK
| | - Kjell Arne Johansson
- Department of Addiction Medicine, Helse Bergen HF, Bergen, Norway
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
| | - Lars T Fadnes
- Department of Addiction Medicine, Helse Bergen HF, Bergen, Norway
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
| |
Collapse
|
|
16
|
Lionetti R, Piccolo P, Lenci I, Siciliano M, Visco-Comandini U, De Santis A, Pompili M, Milana M, Taibi C, Dell'Isola S, Montalbano M, Mastroianni C, Begini P, Garbuglia AR, Angelico M, D'Offizi G. Daclatasvir, sofosbuvir with or without ribavirin for 24 weeks in hepatitis C genotype 3 cirrhosis: A real-life study. Ann Hepatol 2020; 18:434-438. [PMID: 31023614 DOI: 10.1016/j.aohep.2018.09.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 09/02/2018] [Accepted: 09/05/2018] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Cirrhotic patients with hepatitis C virus genotype 3 infection show unsatisfactory outcomes after 12 weeks' treatment with direct antiviral agents. The National Italian Drug Agency allows 24 weeks of therapy in difficult-to-treat patients, including genotype 3 cirrhotics. Aim of this study was to evaluate efficacy and safety of a 24-week course of sofosbuvir plus daclatasvir±ribavirin in this population. MATERIALS AND METHODS 106 consecutive cirrhotics (70.8% males, mean age 55.3±7.6 years) in 8 tertiary hepatology centers received sofosbuvir plus daclatasvir for 24 weeks. Ribavirin was administered in 85 (80.2%) based expected tolerability, at a mean dose of 964±202mg/day. Baseline Child-Pugh class was A 91.5%, B 6.6%, C 1.9%; mean baseline MELD was 8.5±2.7. RESULTS All patients completed 12-week follow-up post-treatment, and 104 (98.1%) obtained sustained virological response (100% in ribavirin -treated patients vs. 90.4% without ribavirin; p=0.04). No worsening in renal and liver function was observed, no serious adverse events occurred. Two virological failures showed resistance associated variants (Y93H and S282T). CONCLUSION An extended 24-week treatment with sofosbuvir plus daclatasvir+ribavirin obtained 100% efficacy in genotype 3 hepatitis C cirrhosis, with very limited side effects. The role of ribavirin seems crucial in this setting and should be administered if clinically feasible.
Collapse
Affiliation(s)
- Raffaella Lionetti
- Liver and Infectious Diseases, Lazzaro Spallanzani National Institute for Infectious Disease, Rome, Italy.
| | - Paola Piccolo
- Internal Medicine Unit, Fatebenefratelli Hospital Isola Tiberina, Rome, Italy; Liver Unit, Tor Vergata University Hospital, Rome, Italy
| | - Ilaria Lenci
- Liver Unit, Tor Vergata University Hospital, Rome, Italy
| | - Massimo Siciliano
- Gastroenterology and Liver Unit, Policlinico Gemelli, Catholic University, Rome, Italy
| | - Ubaldo Visco-Comandini
- Liver and Infectious Diseases, Lazzaro Spallanzani National Institute for Infectious Disease, Rome, Italy
| | - Adriano De Santis
- Gastroenterology and Liver Unit, Policlinico Umberto I, Sapienza University, Rome, Italy
| | - Maurizio Pompili
- Gastroenterology and Liver Unit, Policlinico Gemelli, Catholic University, Rome, Italy
| | - Martina Milana
- Liver Unit, Tor Vergata University Hospital, Rome, Italy
| | - Chiara Taibi
- Liver and Infectious Diseases, Lazzaro Spallanzani National Institute for Infectious Disease, Rome, Italy
| | - Serena Dell'Isola
- Medicina Protetta-Infectious Diseases, Belcolle Hospital, Viterbo, Italy
| | - Marzia Montalbano
- Liver and Infectious Diseases, Lazzaro Spallanzani National Institute for Infectious Disease, Rome, Italy
| | - Claudio Mastroianni
- Infectious Diseases, Policlinico Umberto I, Sapienza University, Rome, Italy
| | - Paola Begini
- Liver Unit, Sant'Andrea University Hospital, Rome, Italy
| | - Anna Rosa Garbuglia
- Laboratory of Virology, Lazzaro Spallanzani National Institute for Infectious Disease, Rome, Italy
| | - Mario Angelico
- Liver Unit, Tor Vergata University Hospital, Rome, Italy
| | - Gianpiero D'Offizi
- Liver and Infectious Diseases, Lazzaro Spallanzani National Institute for Infectious Disease, Rome, Italy
| |
Collapse
|
|
17
|
Sofosbuvir and Ribavirin Combination Therapy Response in Various Hepatitis C Virus Genotypes in Peshawar, Khyber Pakhtunkhwa. Jundishapur J Microbiol 2020. [DOI: 10.5812/jjm.99625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Background: Approximately 3% of the population worldwide is infected with Hepatitis C Virus (HCV). Different regimens have been used to treat HCV, each of which has its side effects and efficacy. Sofosbuvir, a direct-acting antiviral drug, has replaced all previous regimens with the highest response rate. However, its response is not fully covered in Pakistan, especially Khyber Pakhtunkhwa. Objectives: The study aimed to examine the response to Sofosbuvir and Ribavirin combination therapy in chronic HCV patients infected with various HCV genotypes. Methods: This study was conducted in Tertiary Care Hospitals, Peshawar, Pakistan. The patients were enrolled from January 2016 to March 2017. A total of 80 patients (57 naïve and 23 non-responder) were enrolled in this study. The age range was 16 - 70 years, and the mean age was 36 ± 2 years. Genotyping, biochemical profile, PCR tests, and liver ultrasounds were done for all of the enrolled subjects at the start and end of therapy. All patients were given direct-acting antiviral drugs for six months and then, the end of treatment response was noted. Results: A total of 80 subjects with HCV infection took part in the study, including 57 (71.25%) treatment-naïve and 23 (28.75%) treatment non-responding patients. The end of therapy response was reported after 24 weeks of treatment. Among the 80 patients, 72 (90%) patients achieved the end of therapy response. The highest end of therapy response (100%) was noted in genotype 1 and mixed genotypes and patients with normal liver ultrasound. The lowest end of therapy response (70%) was found in un-type genotype and patients with an abnormal texture of liver ultrasound. The end of therapy response rate was higher in females than in males. Conclusions: In the current study, the minimal response was found in un-type genotypes and genotypes that did not respond to INF, as compared to treatment-naïve subjects. Further research is needed to understand the relevant host and viral factors, with particular attention to relapsed patients and non-responders that are difficult to treat in the Pakistani population.
Collapse
|
|
18
|
Zarębska-Michaluk D, Flisiak R, Jaroszewicz J, Janczewska E, Czauż-Andrzejuk A, Berak H, Horban A, Staniaszek A, Gietka A, Tudrujek M, Tomasiewicz K, Dybowska D, Halota W, Piekarska A, Sitko M, Garlicki A, Orłowska I, Simon K, Belica-Wdowik T, Baka-Ćwierz B, Mazur W, Białkowska J, Socha Ł, Wawrzynowicz-Syczewska M, Laurans Ł, Deroń Z, Lorenc B, Dobracka B, Tronina O, Pawłowska M. Is Interferon-Based Treatment of Viral Hepatitis C Genotype 3 Infection Still of Value in the Era of Direct-Acting Antivirals? J Interferon Cytokine Res 2019; 38:93-100. [PMID: 29443655 DOI: 10.1089/jir.2017.0113] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
The aim of the study is to analyze treatments available for patients infected with genotype (G) 3 hepatitis C virus (HCV) in Poland at the beginning of the interferon (IFN)-free era and evaluate the efficacy and safety of different therapeutic options administered in a real-world setting. We analyzed data of 198 patients who started antiviral therapy after July 1, 2015, and completed it before December 31, 2016; 57.6% of them had liver cirrhosis and 46% were treatment experienced. Fifty percent of patients were assigned to sofosbuvir (SOF)+pegylated IFN alfa (PegIFNa)+ribavirin (RBV), 9% to PegIFNa+RBV, 36% received SOF+RBV, and 5% SOF+daclatasvir (DCV)±RBV. Cirrhotic patients were assigned more frequently to IFN-free regimens. Overall, a sustained virological response was achieved by 84.3% of patients in intent-to-treat (ITT) analysis and 87% in modified ITT analysis. For SOF+PegIFNa+RBV and SOF+DCV±RBV regimens, the sustained virologic response (SVR) rate reached at least 90%, whereas the two other therapeutic options demonstrated efficacy <80%. The SVR rate in noncirrhotics was higher than in cirrhotics, irrespective of regimen. Adverse events were documented in 52.5%, with the most common being weakness/fatigue and anemia. We confirmed effectiveness and safety of the SOF-based treatment in a real-world cohort of patients with chronic HCV G3 infection. Most notably, we demonstrated good tolerability and high efficacy of the SOF+PegIFNa+RBV regimen.
Collapse
Affiliation(s)
- Dorota Zarębska-Michaluk
- 1 Department of Infectious Diseases, Voivodship Hospital and Jan Kochanowski University , Kielce, Poland
| | - Robert Flisiak
- 2 Department of Infectious Diseases and Hepatology, Medical University of Białystok , Białystok, Poland
| | - Jerzy Jaroszewicz
- 3 Department of Infectious Diseases and Hepatology, Medical University of Silesia in Katowice , Bytom, Poland
| | | | - Agnieszka Czauż-Andrzejuk
- 2 Department of Infectious Diseases and Hepatology, Medical University of Białystok , Białystok, Poland
| | - Hanna Berak
- 5 Hospital for Infectious Diseases in Warsaw , Warsaw, Poland
| | - Andrzej Horban
- 5 Hospital for Infectious Diseases in Warsaw , Warsaw, Poland
| | - Agnieszka Staniaszek
- 6 Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration , Warsaw, Poland
| | - Andrzej Gietka
- 6 Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration , Warsaw, Poland
| | - Magdalena Tudrujek
- 7 Department of Infectious Diseases and Hepatology, Medical University of Lublin , Lublin, Poland
| | - Krzysztof Tomasiewicz
- 7 Department of Infectious Diseases and Hepatology, Medical University of Lublin , Lublin, Poland
| | - Dorota Dybowska
- 8 Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Toruń , Bydgoszcz, Poland
| | - Waldemar Halota
- 8 Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Toruń , Bydgoszcz, Poland
| | - Anna Piekarska
- 9 Department of Infectious Diseases and Hepatology, Medical University of Łódź , Łódź, Poland
| | - Marek Sitko
- 10 Department of Infectious and Tropical Diseases, Jagiellonian University Collegium Medicum , Kraków, Poland
| | - Aleksander Garlicki
- 10 Department of Infectious and Tropical Diseases, Jagiellonian University Collegium Medicum , Kraków, Poland
| | - Iwona Orłowska
- 11 Department of Infectious Diseases and Hepatology, Wrocław Medical University , Wrocław, Poland
| | - Krzysztof Simon
- 11 Department of Infectious Diseases and Hepatology, Wrocław Medical University , Wrocław, Poland
| | - Teresa Belica-Wdowik
- 12 Regional Center for Diagnosis and Treatment of Viral Hepatitis and Hepatology , John Paul II Hospital, Kraków, Poland
| | - Barbara Baka-Ćwierz
- 12 Regional Center for Diagnosis and Treatment of Viral Hepatitis and Hepatology , John Paul II Hospital, Kraków, Poland
| | - Włodzimierz Mazur
- 13 Clinical Department of Infectious Diseases, Specialist Hospital in Chorzów, Medical University of Silesia , Katowice, Chorzów, Poland
| | - Jolanta Białkowska
- 14 Department of Infectious and Liver Diseases, Medical University of Łódź , Łódź, Poland
| | - Łukasz Socha
- 15 Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University , Szczecin, Poland
| | - Marta Wawrzynowicz-Syczewska
- 15 Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University , Szczecin, Poland
| | - Łukasz Laurans
- 15 Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University , Szczecin, Poland .,16 Multidisciplinary Regional Hospital in Gorzów Wielkopolski , Gorzów Wielkopolski, Poland
| | - Zbigniew Deroń
- 17 Ward of Infectious Diseases and Hepatology, Biegański Regional Specialist Hospital , Łódź, Poland
| | - Beata Lorenc
- 18 Pomeranian Center of Infectious Diseases, Department of Infectious Diseases, Medical University of Gdańsk , Gdańsk, Poland
| | | | - Olga Tronina
- 20 Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw , Warsaw, Poland
| | - Małgorzata Pawłowska
- 8 Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Toruń , Bydgoszcz, Poland
| |
Collapse
|
|
19
|
Welzel TM, Yang M, Sajeev G, Chen YJ, Pinsky B, Bao Y, Wu EQ, Dieterich D. Assessing Patient Preferences for Treatment Decisions for New Direct Acting Antiviral (DAA) Therapies for Chronic Hepatitis C Virus Infections. Adv Ther 2019; 36:2475-2486. [PMID: 31240629 PMCID: PMC6822851 DOI: 10.1007/s12325-019-01012-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Indexed: 01/27/2023]
Abstract
INTRODUCTION The new direct acting antiviral (DAA) therapies are able to effectively treat chronic hepatitis C (CHC). This study elicited the preferences of CHC patients for treatment attributes of new DAAs. METHODS An online discrete choice experiment survey was designed to collect data from adult CHC patients in the USA, UK, France, Germany, Spain, and Italy. Patients were asked to choose from alternative hypothetical DAA options, defined by differing levels of nine attributes [i.e., treatment duration, tablet count and packaging, cure rate, required office visits when on treatment, modifications to statins or to proton pump inhibitors (PPIs), and risks of diarrhea, headache and nausea]. Logistic regression was used to assess preference for the treatment options. RESULTS A total of 328 patients with CHC completed the survey (USA, n = 227; European countries, n = 101), with a mean age of 47.7 years (SD = 14.4) and an average 11.2 years since CHC diagnosis; 51% of patients were female. More than half (60%) of the patients had treatment for CHC. Patients significantly preferred a DAA regimen with higher cure rate, shorter treatment duration, lower risks of diarrhea, headache, and nausea (all p < 0.001), reduced need for office visits when on treatment (p = 0.044), and without requiring dose reduction or timing change in PPIs (p = 0.032). Tablet counts were not found to be statistically significant. CONCLUSION Given the overall high cure rates of new DAAs, CHC patients' preferences for therapy may be influenced by treatment attributes other than cure rates and tolerability. Treatments that are more convenient and require less disruption to their daily life (e.g., shorter treatment duration, no modification in PPI use, and fewer office visits when on treatment) are important to patients with CHC and should be considered when making treatment decisions. FUNDING AbbVie.
Collapse
Affiliation(s)
| | - Min Yang
- Analysis Group, Inc., Boston, MA, USA
| | | | | | | | | | - Eric Q Wu
- Analysis Group, Inc., Boston, MA, USA
| | | |
Collapse
|
|
20
|
Colombo MG, Musabaev EI, Ismailov UY, Zaytsev IA, Nersesov AV, Anastasiy IA, Karpov IA, Golubovska OA, Kaliaskarova KS, AC R, Hadigal S. Consensus on management of hepatitis C virus infection in resource-limited Ukraine and Commonwealth of Independent States regions. World J Gastroenterol 2019; 25:3897-3919. [PMID: 31413526 PMCID: PMC6689802 DOI: 10.3748/wjg.v25.i29.3897] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Revised: 06/04/2019] [Accepted: 06/08/2019] [Indexed: 02/06/2023] Open
Abstract
Globally, 69.6 million individuals were infected with hepatitis C virus (HCV) infection in 2016. Of the six major HCV genotypes (GT), the most predominant one is GT1, worldwide. The prevalence of HCV in Central Asia, which includes most of the Commonwealth of Independent States (CIS), has been estimated to be 5.8% of the total global burden. The predominant genotype in the CIS and Ukraine regions has been reported to be GT1, followed by GT3. Inadequate HCV epidemiological data, multiple socio-economic barriers, and the lack of region-specific guidelines have impeded the optimal management of HCV infection in this region. In this regard, a panel of regional experts in the field of hepatology convened to discuss and provide recommendations on the diagnosis, treatment, and pre-, on-, and posttreatment assessment of chronic HCV infection and to ensure the optimal use of cost-effective antiviral regimens in the region. A comprehensive evaluation of the literature along with expert recommendations for the management of GT1-GT6 HCV infection with the antiviral agents available in the region has been provided in this review. This consensus document will help guide clinical decision-making during the management of HCV infection, further optimizing treatment outcomes in these regions.
Collapse
Affiliation(s)
- Massimo Giuseppe Colombo
- Research and Clinical Center, Department of Medicine, Humanitas Hospital, Rozzano 20089, MI, Italy
| | - Erkin Isakovich Musabaev
- Research Institute of Virology, Scientific Research Institute of Virology, Tashkent 100194, Uzbekistan
| | - Umed Yusupovich Ismailov
- Hepatoсenter, Research Institute of Virology, Scientific Research Institute of Virology, Tashkent 100194, Uzbekistan
| | - Igor A Zaytsev
- Department of Therapy, Infectious Diseases and Dermatology, Bogomolets National Medical University, Kyiv 01601, Ukraine
| | - Alexander V Nersesov
- Department of Gastroenterology and Hepatology, National Research Institute of Cardiology and Internal Diseases, Almaty 050000, Kazakhstan
| | | | | | - Olga A Golubovska
- Department Infectious Diseases, Bogomolets National Medical University, Kyiv 01601, Ukraine
| | | | - Ravishankar AC
- Medical Affairs, Mylan Pharmaceuticals Private Limited, Kadubeesanahalli, Bengaluru 560103, India
| | - Sanjay Hadigal
- Medical Affairs, Mylan Pharmaceuticals Private Limited, Kadubeesanahalli, Bengaluru 560103, India
| |
Collapse
|
|
21
|
Salmon D, Trimoulet P, Gilbert C, Solas C, Lafourcade E, Chas J, Piroth L, Lacombe K, Katlama C, Peytavin G, Aumaitre H, Alric L, Boué F, Morlat P, Poizot-Martin I, Billaud E, Rosenthal E, Naqvi A, Miailhes P, Bani-Sadr F, Esterle L, Carrieri P, Dabis F, Sogni P, Wittkop L. Factors associated with DAA virological treatment failure and resistance-associated substitutions description in HIV/HCV coinfected patients. World J Hepatol 2018; 10:856-866. [PMID: 30533186 PMCID: PMC6280155 DOI: 10.4254/wjh.v10.i11.856] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Revised: 09/10/2018] [Accepted: 10/10/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To describe factors associated with treatment failure and frequency of resistance-associated substitutions (RAS).
METHODS Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients starting a first direct-acting antiviral (DAA) regimen before February 2016 and included in the French ANRS CO13 HEPAVIH cohort were eligible. Failure was defined as: (1) non-response [HCV-RNA remained detectable during treatment, at end of treatment (EOT)]; and (2) relapse (HCV-RNA suppressed at EOT but detectable thereafter). Sequencing analysis was performed to describe prevalence of drug class-specific RAS. Factors associated with failure were determined using logistic regression models.
RESULTS Among 559 patients, 77% had suppressed plasma HIV-RNA < 50 copies/mL at DAA treatment initiation, 41% were cirrhotic, and 68% were HCV treatment-experienced. Virological treatment failures occurred in 22 patients and were mainly relapses (17, 77%) then undefined failures (3, 14%) and non-responses (2, 9%). Mean treatment duration was 16 wk overall. Post-treatment NS3, NS5A or NS5B RAS were detected in 10/14 patients with samples available for sequencing analysis. After adjustment for age, sex, ribavirin use, HCV genotype and treatment duration, low platelet count was the only factor significantly associated with a higher risk of failure (OR: 6.5; 95%CI: 1.8-22.6).
CONCLUSION Only 3.9% HIV-HCV coinfected patients failed DAA regimens and RAS were found in 70% of those failing. Low platelet count was independently associated with virological failure.
Collapse
Affiliation(s)
- Dominique Salmon
- Assistance Publique des Hôpitaux de Paris, Hôpitaux Universitaires Paris Centre, Hôpital Hôtel Dieu, Unité des Maladies infectieuses et tropicales, Paris 75004, France
- Université Paris Descartes, Sorbonne Paris Cité, Paris 75006, France
| | - Pascale Trimoulet
- CHU de Bordeaux, Hôpital Pellegrin, Laboratoire de Virologie, Bordeaux 33000, France
- CNRS-UMR 5234, Microbiologie fondamentale et Pathogénicité, Université de Bordeaux, Bordeaux 3000, France
| | - Camille Gilbert
- Univ. Bordeaux, ISPED, Inserm, Bordeaux Population Health Research Center, team MORPH3EUS, UMR 1219, CIC-EC 1401, Bordeaux F-33000, France
| | - Caroline Solas
- APHM, Hôpital La Timone, Laboratoire de Pharmacocinétique et Toxicologie, Marseille 13005, France
| | - Eva Lafourcade
- Univ. Bordeaux, ISPED, Inserm, Bordeaux Population Health Research Center, team MORPH3EUS, UMR 1219, CIC-EC 1401, Bordeaux F-33000, France
| | - Julie Chas
- Assistance Publique des Hôpitaux de Paris, Hôpital Tenon, Service Maladies infectieuses et tropicales, Paris 75020, France
| | - Lionel Piroth
- Centre Hospitalier Universitaire de Dijon, Département d’Infectiologie, Dijon cedex 21079, France
- INSERM-CIC 1342 Université de Bourgogne, Dijon 21000, France
| | - Karine Lacombe
- Assistance Publique des Hôpitaux de Paris, GHUEP site Saint-Antoine, Services Maladies infectieuses et tropicales, Paris 75011, France
- Université Pierre et Marie Curie, UMR S1136, Institut Pierre Louis d’Epidémiologie et de Santé Publique, Paris 75646, France
| | - Christine Katlama
- Université Paris-Sorbonne, Paris 75005, France
- Assistance Publique des Hôpitaux de Paris Hôpital Pitié Salpêtrière, Services Maladies infectieuses et tropicales, Paris 75013, France
| | - Gilles Peytavin
- Assistance Publique des Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Laboratoire de Pharmacologie, Paris 75877, France
- IAME, UMR 1137, Sorbonne Paris Cité, INSERM, Université Paris Diderot, Paris 75890, France
| | - Hugues Aumaitre
- Centre Hospitalier de Perpignan, Service Maladies infectieuses et tropicales, Perpignan 66000, France
| | - Laurent Alric
- Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Service Médecine interne-Pôle Digestif, Toulouse 31300, France
- UMR 152 IRD Université Toulouse III, Paul Sabatier, Toulouse 31330, France
| | - François Boué
- Hôpital Antoine-Béclère, Assistance Publique des Hôpitaux de Paris, Université Paris Sud, Service Médecine interne et immunologie, Clamart 92140, France
| | - Philippe Morlat
- Univ. Bordeaux, ISPED, Inserm, Bordeaux Population Health Research Center, team MORPH3EUS, UMR 1219, CIC-EC 1401, Bordeaux F-33000, France
- Centre Hospitalier Universitaire de Bordeaux, Service de médecine interne, Hôpital Saint-André, Bordeaux 33000, France
| | - Isabelle Poizot-Martin
- Aix-Marseille Univ, APHM Sainte-Marguerite, Service d’Immuno-hématologie clinique, Marseille 13274, France
- Sciences Economiques and Sociales de la Santéand Traitement de l’Information Médicale, UMR912 INSERM, Aix-Marseille Université, IRD, Marseille 13009, France
| | - Eric Billaud
- Department of Infectious Diseases, CHU de Nantes and CIC 1413, Inserm, Nantes 44000, France
| | - Eric Rosenthal
- Centre Hospitalier Universitaire de Nice, Service de Médecine Interne, Hôpital l’Archet, Nice 06202, France
- Université de Nice-Sophia Antipolis, Nice 06100, France
| | - Alissa Naqvi
- Centre Hospitalier Universitaire de Nice, Service d’Infectiologie, Hôpital l’Archet, Nice 06100, France
| | - Patrick Miailhes
- Service des Maladies Infectieuses et Tropicales, Hospices Civils de Lyon, Hôpital de la Croix Rousse, Lyon 69004, France
| | - Firouzé Bani-Sadr
- Centre Hospitalier Universitaire de Reims, Service de Médecine Interne, Maladies Infectieuses et Immunologie Clinique, Reims 51100, France
- Faculté de Médecine EA-4684/SFR CAP-SANTE, Université de Reims, Champagne-Ardenne, Reims 51100, France
| | - Laure Esterle
- Univ. Bordeaux, ISPED, Inserm, Bordeaux Population Health Research Center, team MORPH3EUS, UMR 1219, CIC-EC 1401, Bordeaux F-33000, France
| | - Patrizia Carrieri
- Sciences Economiques and Sociales de la Santéand Traitement de l’Information Médicale, UMR912 INSERM, Aix-Marseille Université, IRD, Marseille 13009, France
| | - François Dabis
- Univ. Bordeaux, ISPED, Inserm, Bordeaux Population Health Research Center, team MORPH3EUS, UMR 1219, CIC-EC 1401, Bordeaux F-33000, France
| | - Philippe Sogni
- Assistance Publique des Hôpitaux de Paris, Hôpital Cochin, Service d’Hépatologie, Paris 75014, France
- Inserm U-1223 - Institut Pasteur, Paris 75015, France
| | - Linda Wittkop
- Univ. Bordeaux, ISPED, Inserm, Bordeaux Population Health Research Center, team MORPH3EUS, UMR 1219, CIC-EC 1401, Bordeaux F-33000, France
- CHU de Bordeaux, Pôle de santé Publique, Service dâinformation médicale, Bordeaux F-33000, France
| | | |
Collapse
|
|
22
|
Sølund C, Hallager S, Pedersen MS, Fahnøe U, Ernst A, Krarup HB, Røge BT, Christensen PB, Laursen AL, Gerstoft J, Bélard E, Madsen LG, Schønning K, Pedersen AG, Bukh J, Weis N. Direct acting antiviral treatment of chronic hepatitis C in Denmark: factors associated with and barriers to treatment initiation. Scand J Gastroenterol 2018; 53:849-856. [PMID: 29720023 DOI: 10.1080/00365521.2018.1467963] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES We describe factors associated with and barriers to initiation of Direct Acting Antiviral (DAA) treatment in patients with chronic hepatitis C, who fulfill national fibrosis treatment guidelines in Denmark. MATERIALS AND METHODS In this nationwide cohort study, we included patients with chronic hepatitis C from The Danish Database for Hepatitis B and C (DANHEP) who fulfilled fibrosis treatment criteria. Factors associated with treatment initiation and treatment failure were determined by logistic regression analyses. Medical records were reviewed from patients who fulfilled fibrosis treatment criteria, but did not initiate DAA treatment to determine the cause. RESULTS In 344 (49%) of 700 patients, who fulfilled treatment criteria, factors associated with DAA treatment initiation were transmission by other routes than injecting drug use odds ratio (OR) 2.13 (CI: 1.38-3.28), previous treatment failure OR 2.58 (CI: 1.84-3.61) and ALT above upper limit of normal OR 1.60 (CI: 1.18-2.17). The most frequent reasons for not starting treatment among 356 (51%) patients were non-adherence to medical appointments (n = 107/30%) and ongoing substance use (n = 61/17%). Treatment failure with viral relapse occurred in 19 (5.5%) patients, who were more likely to have failed previous treatment OR 4.53 (CI: 1.59-12.91). CONCLUSIONS In this nationwide cohort study, we found non-adherence to medical appointments and active substance use to be major obstacles for DAA treatment initiation. Our findings highlight the need for interventions that can overcome these barriers and increase the number of patients who can initiate and benefit from curative DAA treatment.
Collapse
Affiliation(s)
- Christina Sølund
- a Department of Infectious Diseases , Copenhagen University Hospital , Hvidovre , Denmark.,b Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark
| | - Sofie Hallager
- a Department of Infectious Diseases , Copenhagen University Hospital , Hvidovre , Denmark
| | - Martin S Pedersen
- b Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.,c Department of Clinical Microbiology , Copenhagen University Hospital , Hvidovre , Denmark.,d Department of Science and Environment , Roskilde University , Roskilde , Denmark
| | - Ulrik Fahnøe
- b Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark
| | - Anja Ernst
- e Department of Molecular Diagnostics , Aalborg University Hospital , Aalborg , Denmark
| | - Henrik B Krarup
- e Department of Molecular Diagnostics , Aalborg University Hospital , Aalborg , Denmark.,f Department of Medical Gastroenterology , Aalborg University Hospital , Aalborg , Denmark
| | - Birgit T Røge
- g Department of Medicine , Lillebaelt Hospital , Kolding , Denmark
| | - Peer B Christensen
- h Department of Infectious Diseases , Odense University Hospital , Odense , Denmark.,i Department of Clinical Research, Faculty of Health Sciences , University of Southern Denmark , Odense , Denmark
| | - Alex L Laursen
- j Department of Infectious Diseases , Aarhus University Hospital , Skejby , Denmark
| | - Jan Gerstoft
- k Department of Infectious Diseases , Copenhagen University Hospital, Rigshospitalet , Copenhagen , Denmark.,l Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark
| | - Erika Bélard
- m Department of Gastroenterology , Copenhagen University Hospital , Herlev , Denmark
| | - Lone G Madsen
- l Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.,n Department of Medical Gastroenterology , Zealand University Hospital , Køge , Denmark
| | - Kristian Schønning
- c Department of Clinical Microbiology , Copenhagen University Hospital , Hvidovre , Denmark.,l Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark
| | - Anders G Pedersen
- o DTU Bioinformatics , Technical University of Denmark , Lyngby , Denmark
| | - Jens Bukh
- a Department of Infectious Diseases , Copenhagen University Hospital , Hvidovre , Denmark.,b Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark
| | - Nina Weis
- a Department of Infectious Diseases , Copenhagen University Hospital , Hvidovre , Denmark.,l Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark
| | | |
Collapse
|
|
23
|
Pham TT, Keast SL, Farmer KC, Thompson DM, Rathbun RC, Nesser NJ, Holderread BP, Skrepnek GH. Sustained Virologic Response and Costs Associated with Direct-Acting Antivirals for Chronic Hepatitis C Infection in Oklahoma Medicaid. J Manag Care Spec Pharm 2018; 24:664-676. [PMID: 29952711 PMCID: PMC10398076 DOI: 10.18553/jmcp.2018.24.7.664] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
BACKGROUND Outcomes involving newer direct-acting antiviral (DAA) hepatitis C virus (HCV) regimens have not been studied extensively among the Medicaid population. OBJECTIVE To assess clinical (treatment failure) and economic outcomes for chronic HCV-infected Oklahoma Medicaid members following treatment with DAAs and to measure associations with patient, treatment, and clinical characteristics. METHODS This cross-sectional study used Oklahoma Medicaid pharmacy and medical claims data for adult members who used a newer DAA agent and had reported a successful or failed sustained virological response rate 12 weeks after therapy completion (SVR12) from January 1, 2014, to June 30, 2016. Multivariable logistic and gamma regressions assessed predictors of SVR12 failure and costs controlling for member demographics (i.e., age, sex, race, rural residence); type of DAA and adherence; clinical characteristics (e.g., comorbid conditions, advanced liver disease); and the implementation of changes to a prior authorization program. RESULTS Of 934 Medicaid members eligible for treatment with DAAs between January 1, 2014, and June 30, 2016, 906 received DAA treatment, 40.6% (368/906) had reported SVR12 outcomes, and 59.4% (n = 538) did not have a reported SVR recorded. Of those with reported SVR12 outcomes, patients were 53.1 ± 9.7 years of age, 51.1% were male, 8.4% had SVR12 failure, and each member had mean costs of $140,283 ± $52,779. Multivariable analyses indicated higher odds of SVR12 failure was independently associated with cirrhosis (OR [decompensated] = 6.69 and OR [compensated] = 3.52, P < 0.001), while males had higher odds of failure than females (OR = 3.34, P < 0.010). No significant difference in SVR12 failure was noted, according to DAA type or a medication adherence threshold of > 95%. Ledipasvir/sofosbuvir was independently associated with lower costs (exp[b] = 0.81; P < 0.001) compared with sofosbuvir, while higher costs were associated with decompensated cirrhosis (exp[b] = 1.22; P < 0.001) and treatment failure (exp[b] = 1.18, P < 0.010). In an analysis including members without reported SVR12 outcomes, decompensated and compensated cirrhosis had lower odds (P < 0.001) of no reported SVR12 from ambulatory clinic settings. CONCLUSIONS Almost 60% of Medicaid members receiving DAA treatment did not have a final reported SVR12 outcome. Among those with viral load measurements, treatment success was high and both decompensated and compensated cirrhosis were independently associated with significantly higher odds of treatment failure. Addressing a loss to follow-up among HCV patients and curtailing the development of cirrhosis to improve treatment success may warrant interventions that improve access to care and remove barriers that impede treatment initiation and completion. DISCLOSURES No outside funding supported this study. Pham, Keast, Holderread, Nesser, and Skrepnek disclose either employment by the Oklahoma Health Care Authority or contractual work for this employer. Pham discloses fellowship funding from Purdue Pharma unrelated to this study. Keast and Skrepnek disclose research grant funding from Gilead Sciences and Abbvie. Holderread also reports grant funding from Gilead Sciences and fees from PRIME Education. Thompson, Farmer, and Rathbun have nothing to disclose.
Collapse
Affiliation(s)
- Timothy T Pham
- 1 University of Oklahoma College of Pharmacy, Oklahoma City
| | | | - Kevin C Farmer
- 1 University of Oklahoma College of Pharmacy, Oklahoma City
| | - David M Thompson
- 2 University of Oklahoma College of Public Health, Oklahoma City
| | | | | | | | | |
Collapse
|
|
24
|
Introduction of the second-generation direct-acting antivirals (DAAs) in chronic hepatitis C: a register-based study in Sweden. Eur J Clin Pharmacol 2018; 74:971-978. [PMID: 29632961 PMCID: PMC5999144 DOI: 10.1007/s00228-018-2456-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2017] [Accepted: 03/21/2018] [Indexed: 01/10/2023]
Abstract
PURPOSE Introduction of the direct-acting antivirals (DAAs) for treatment of chronic hepatitis C (CHC) infection has been challenging in all health systems. In Sweden, a national protocol for managed introduction was developed. It was optional, but all county councils agreed to implement and follow it. The purpose of this study was to study (a) cure rates among all patients initiated on treatment in 2014-2015, (b) prescribers' adherence to the drug recommendations and treatment eligibility criteria in the protocol, and (c) introduction rate in the six Swedish healthcare regions. METHOD A cross-sectional study where national data from the Prescribed Drug Register and the quality register InfCare Hepatitis defined the study population, and clinical data from the Patient Register and InfCare Hepatitis were used to monitor outcomes. Descriptive statistics were used. RESULTS A total of 3447 patients were initiated on treatment during 2014-2015. The overall cure rate, based on data from 85% of the cohort, was 96%, with variation between genotypes. Adherence to drug recommendations increased over time and varied between 43.2 and 94.2%. Adherence to the treatment eligibility criteria was initially 80% and increased to 87% when treatment restrictions were widened. The introduction rate differed initially between the regions and reached stable levels 15-18 months after the launch of the first DAA. CONCLUSION The estimated overall cure rate was 96%, with some variations between genotypes. A high level of adherence to the introduction protocol as well as similar introduction rates in the health care regions indicate that the introduction protocol, alongside with other measures taken, contributed considerably to a rapid uptake and equal distribution of DAAs in Sweden.
Collapse
|
|
25
|
Jamil Z, Waheed Y, Malik M, Durrani AA. Effect of Sofosbuvir plus Ribavirin therapy on hepatitis C patients in Pakistan: a retrospective study. PeerJ 2018; 6:e4853. [PMID: 29844992 PMCID: PMC5971832 DOI: 10.7717/peerj.4853] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Accepted: 05/04/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The annual global deaths from viral hepatitis is 1.4 million. Pakistan has the second highest burden of hepatitis C in the world. There is dire need to evaluate the response of new direct acting antivirals for the treatment of hepatitis C patients in Pakistan. World Health Organization has developed a strategy to treat 80% of HCV patients by 2030. In Pakistan, HCV treatment rate is 1%. The aim of the study was to analyze the effect of Sofosbuvir plus Ribavirin therapy on HCV patients in Pakistan. METHODS An observational study was conducted at Fauji Foundation Hospital Rawalpindi from November-2016 to July-2017. All the drugs were administered according to the guidelines of Asia Pacific Association for the Study of Liver (APASL) for the treatment of HCV patients. A total 327 chronic HCV patients were enrolled in the study and 304 completed the treatment. Patients belonged to three different groups including treatment: Naïve patients (n = 107), Non-Responder patients (n = 126) and patients who relapsed to Interferon therapy (n = 71). All the patients were given Sofosbuvir plus Ribavirin therapy for 24 weeks and the early virological response (EVR) and end treatment response (ETR) was calculated. Different parameters including patient age, viral load, viral genotype, blood picture, ultrasound findings and liver function tests were also studied. RESULTS Out of 304 patients, 301 (99%) achieved EVR and 300 achieved ETR (98.7%). End treatment response was 95.6% in HCV genotype 1 and 98.9% in HCV genotype 3 patients. ETR was 99.06% in treatment Naïve, 99.20% in non-responders and 97.18% in previously relapsed patients. We did not find the association of any host and viral factor in the determination of EVR and ETR. CONCLUSION The Sofosbuvir plus Ribavirin treatment is highly effective, safe and cost-effective for the treatment of hepatitis C patients in Pakistan.
Collapse
Affiliation(s)
- Zubia Jamil
- Department of Medicine, Foundation University Medical College, Foundation University Islamabad, Islamabad, Pakistan
| | - Yasir Waheed
- Multidisciplinary Laboratory, Foundation University Medical College, Foundation University Islamabad, Islamabad, Pakistan
| | - Maryam Malik
- Department of Medicine, Fauji Foundation Hospital, Rawalpindi, Pakistan
| | - Asghar A. Durrani
- Department of Medicine, Fauji Foundation Hospital, Rawalpindi, Pakistan
| |
Collapse
|