Multicenter Study to Transplant Hepatitis C–Infected Kidneys (MYTHIC): An Open-Label Study of Combined Glecaprevir and Pibrentasvir to Treat Recipients of Transplanted Kidneys from Deceased Donors with Hepatitis C Virus Infection

BackgroundSingle-center trials and retrospective case series have reported promising outcomes using kidneys from donors with hepatitis C virus (HCV) infection. However, multicenter trials are needed to determine if those findings are generalizable.MethodsWe conducted a prospective trial at seven centers to transplant 30 kidneys from deceased donors with HCV viremia into HCV-uninfected recipients, followed by 8 weeks of once-daily coformulated glecaprevir and pibrentasvir, targeted to start 3 days posttransplant. Key outcomes included sustained virologic response (undetectable HCV RNA 12 weeks after completing treatment with glecaprevir and pibrentasvir), adverse events, and allograft function.ResultsWe screened 76 patients and enrolled 63 patients, of whom 30 underwent kidney transplantation from an HCV-viremic deceased donor (median kidney donor profile index, 53%) in May 2019 through October 2019. The median time between consent and transplantation of a kidney from an HCV-viremic donor was 6.3 weeks. All 30 recipients achieved a sustained virologic response. One recipient died of complications of sepsis 4 months after achieving a sustained virologic response. No severe adverse events in any patient were deemed likely related to HCV infection or treatment with glecaprevir and pibrentasvir. Three recipients developed acute cellular rejection, which was borderline in one case. Three recipients developed polyomavirus (BK) viremia near or >10,000 copies/ml that resolved after reduction of immunosuppression. All recipients had good allograft function, with a median creatinine of 1.2 mg/dl and median eGFR of 57 ml/min per 1.73 m2 at 6 months.ConclusionsOur multicenter trial demonstrated safety and efficacy of transplantation of 30 HCV-viremic kidneys into HCV-negative recipients, followed by early initiation of an 8-week regimen of glecaprevir and pibrentasvir.

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Position Paper on Treatment of Hepatitis C in Romania 2017. Part Two

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.263.rom ◽

2017 ◽

Vol 26 (3) ◽

pp. 309-317 ◽

Cited By ~ 3

Author(s):

Liana Gheorghe ◽

Ioan Sporea ◽

Speranța Iacob ◽

Roxana Șirli ◽

Anca Trifan ◽

...

Keyword(s):

Hepatitis C Virus ◽

Liver Disease ◽

Hepatitis C ◽

Sustained Virologic Response ◽

Real Life ◽

Virologic Response ◽

Position Paper ◽

Hcv Infection ◽

End Stage Liver Disease ◽

End Stage

Background & Aims: Hepatitis C virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments have become available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country.Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention was created and these were discussed and rated. Decisions were taken by consensus.Recommendations: We present here the second part of the Society’s recommendations for chronic HCV infection treatment. An agreement between experts was reached regarding the therapy of the special categories of patients infected with HCV, complications and monitoring of the therapy, follow-up of the patients who reached sustained virologic response and re-treatment of the patients with therapy failure.Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to real-life conditions in Romania. Abbreviations: CKD: Chronic kidney disease; DAAs: Direct-acting antivirals; DDIs: Drug-drug interactions; ESDL: End-stage liver disease; FCH: Fibrosing cholestatic hepatitis; GT: Genotype; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; LT: Liver transplantation; MELD score: Mayo-Clinic End-Stage Liver Disease score; PDC: Premature discontinuation; PWID: Persons who inject drugs; RASs: Resistance associated substitutions; RBV: Ribavirin; RCT: Randomized controlled trial; SAE: Serious adverse events; SRGH: Romanian Society of Gastroenterology and Hepatology; SVR: Sustained virologic response.

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Sofosbuvir Plus Daclatasvir in Treatment of Chronic Hepatitis C Genotype 4 Infection in a Cohort of Egyptian Patients: An Experiment the Size of Egyptian Village

International Journal of Hepatology ◽

10.1155/2018/9616234 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5 ◽

Cited By ~ 18

Author(s):

Ossama Ashraf Ahmed ◽

Eslam Safwat ◽

Mohamed Omar Khalifa ◽

Ahmed I. Elshafie ◽

Mohamed Hassan Ahmed Fouad ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Adverse Events ◽

Chronic Hepatitis C ◽

Sustained Virologic Response ◽

Virologic Response ◽

World Health ◽

Genotype 4 ◽

Positive Results

Background and Aims. As indicated by the World Health Organization (WHO), Egypt is positioned as the country with the world’s highest prevalence of Hepatitis C virus (HCV). HCV is transmitted through unexamined blood transfusions, different employments of syringes, and poor cleansing, as per the WHO. Our study aimed at screening and management of chronic hepatitis C genotype 4 infected patients in Bardeen village, Sharkeya Governorate, Egypt, with Sofosbuvir plus Daclatasvir, as well as estimating the safety and efficacy of that regimen. Methods. Screening of adult patients in Bardeen village was done from March 2016 till November 2016 using hepatitis C virus antibodies by third-generation ELISA testing. Positive results were confirmed by PCR. Patients eligible for treatment received Sofosbuvir 400 mg and Daclatasvir 60 mg daily for 12 weeks and were assessed for sustained virologic response at 12 weeks following the end of treatment (SVR 12). Results. Out of 2047 subjects screened for hepatitis C virus, 249 (12.2%) showed positive results. 221 out of those 249 subjects (88.7%) had detectable RNA by PCR. Treatment of eligible patients (183 patients) with Sofosbuvir plus Daclatasvir for 12 weeks resulted in 96% achievement of sustained virologic response at week 12. Adverse events were tolerable. Conclusion. Sofosbuvir plus Daclatasvir regimen is safe and effective for treatment of chronic hepatitis C Genotype 4 infected patients with minimal adverse events. HCV eradication program implemented in Egypt can be a model for other countries with HCV and limited resources. The availability of generic drugs in Egypt will help much in eradication of the virus.

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Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir ± Dasabuvir Regimen in Haemodialysis Patients With Hepatitis C Virus Infection

Infektološki glasnik ◽

10.37797/ig.39.1.4 ◽

2020 ◽

Vol 39 (1) ◽

pp. 23-27

Author(s):

Antonija Verhaz ◽

Tatjana Roganović ◽

Ljiljana Pašić ◽

Olja Čuković ◽

Tanja Macanović-Kostić

Keyword(s):

Liver Cirrhosis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Adverse Events ◽

Concomitant Medication ◽

Demographic Data ◽

Virologic Response ◽

Hcv Infection ◽

Hcv Rna ◽

Stage Renal Disease

Background: Hepatitis C virus (HCV) infection is common among patients on haemodialysis (HD) therapy and is an important cause of morbidity and mortality. In patients with chronic kidney disease (CKD), the risks for negative outcomes are significantly higher in HCV-infected patients than in those without HCV infection, including progression to cirrhosis, hepatocellular carcinoma and liver-related mortality. Ombitasvir (OBV), paritaprevir (PTV), ritonavir (r), and dasabuvir (DSV) are all hepatically metabolized and, therefore, require no dose adjustment in patients with any degree of renal impairment. Aims: We studied the safety and efficacy of OBV/PTV/r + DSV in a small group of HCV infected patients on haemodialysis therapy. Methods: Treatment course with ombitasvir/paritaprevir/ritonavir and dasabuvir; (3-DAA regimen of OBV/PTV/r+DSV±RBV) was analysed. Pre-treatment evaluation of HCV infection included HCV RNA, genotype, and liver fibrosis assed by transient fibroelastography (FibroScan). The stage 5 CKD was defined as an eGFR of <15 mL/min/1.73 m2, respectively; those on haemodialysis were considered to have stage 5 CKD or end-stage renal disease (ESRD). Demographic data and concomitant medication were retrieved from patients’ records. The primary endpoint was sustained virologic response at post-treatment week 12 (SVR12). We collected data on on-treatment adverse events (AEs), serious AEs, and laboratory abnormalities. Results: Among 7 treated patients, 6 were male and 1 female, all were infected with genotype 1 (5 GT1b, 2 GT1a). Patient had compensated liver cirrhosis and six patients did not have liver cirrhosis, none were liver transplant recipients. All of seven patients completed 12 weeks of treatment and achieved SVR12. Concomitant medication had to be modified with the treatment initiation in 5 out of 7 patients. One of the patients presented with a significant decrease in haemoglobin level, white blood cell and platelet count during the treatment period. The most frequent adverse events were nausea, diarrhoea. Adverse events were primarily mild, and no patient discontinued treatment due to an AE. Conclusions: Treatment with OBV/PTV/r +DSV ± RBV was well-tolerated and resulted in high rates of SVR12 (100%) for patients with HCV GT1b/1a on haemodialysis.

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Treatment with Grazoprevir/Elbasvir in Post-kidney Transplant Patients with Hepatitis C Virus Genotype 4 Infection

Hepatitis Monthly ◽

10.5812/hepatmon.110260 ◽

2021 ◽

Vol 21 (4) ◽

Author(s):

Faisal Abaalkhail ◽

Waleed Al-hamoudi ◽

Ibrahim Altraif ◽

Hazem Mohamed ◽

Hassan Aleid ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Adverse Events ◽

Kidney Transplant ◽

Graft Function ◽

Case Series ◽

Hcv Infection ◽

Fixed Dose ◽

Genotype 4 ◽

Hcv Genotype

Background: Kidney transplant (KT) recipients have a high rate of hepatitis C virus (HCV) infection, which can impact long-term graft and patient survival rates. Although direct-acting antivirals (DAAs) are effective for treating HCV, there is limited data on their use in post-KT patients with HCV genotype 4 infection. Objectives: To evaluate the effectiveness and occurrence of adverse events with grazoprevir/elbasvir combination treatment without ribavirin in post-KT patients with HCV genotype 4 infection. Methods: In this case series, nine therapy-naïve adult post-KT patients with HCV genotype 4 infection were recruited. They had stable graft function and received a fixed dose of grazoprevir/elbasvir (50 mg/100 mg) combination without ribavirin daily for 12 weeks. Patients co-infected with hepatitis B virus, HIV, or with evidence of decompensated liver disease were excluded from the study. Patients were monitored for viral load, laboratory values, and adverse events associated with drug treatment. The response was defined by the sustained virologic response at 12 weeks (SVR12) after the end of treatment. Results: All nine patients completed the treatment period and achieved SVR12 with no treatment failure or relapse. Of them, six patients had HCV genotype 4 infection alone, and three had HCV of mixed genotypes 1 and 4. Two (22%) patients showed a rapid HCV clearance at four weeks. No adverse events or serious adverse events were reported. The patients’ renal function was stable during and after the treatment with no deterioration of graft function, and no adjustments to the immunosuppressive therapy were required. Conclusions: Grazoprevir/elbasvir combination without ribavirin is an effective and safe treatment option for post-KT patients with genotype 4 HCV infection.

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295 - Sustained Virologic Response (SVR) to Direct-Acting Antiviral (DAA) Therapy in Patients with Hepatitis C Virus (HCV) Infection and Hepatocellular Carcinoma (HCC): A Systematic Review and Meta-Analysis

Gastroenterology ◽

10.1016/s0016-5085(18)33608-4 ◽

2018 ◽

Vol 154 (6) ◽

pp. S-1082-S-1083

Author(s):

Fanpu Ji ◽

Mike Wei ◽

Yee Hui Yeo ◽

Bin Wei ◽

Eiichi Ogawa ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systematic Review ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Sustained Virologic Response ◽

Meta Analysis ◽

Virologic Response ◽

Hcv Infection ◽

Direct Acting Antiviral ◽

Direct Acting

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Efficacy and Safety of Danoprevir-Ritonavir plus Peginterferon Alfa-2a–Ribavirin in Hepatitis C Virus Genotype 1 Prior Null Responders

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01515-13 ◽

2013 ◽

Vol 58 (2) ◽

pp. 1136-1145 ◽

Cited By ~ 13

Author(s):

Edward J. Gane ◽

Régine Rouzier ◽

Alicja Wiercinska-Drapalo ◽

Dominique G. Larrey ◽

Peter N. Morcos ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Adverse Events ◽

Sustained Virologic Response ◽

Virologic Response ◽

Hcv Rna ◽

Efficacy And Safety ◽

Genotype 1 ◽

Virus Genotype ◽

Peginterferon Alfa

ABSTRACTDanoprevir (DNV) is a hepatitis C virus (HCV) protease inhibitor that achieves high sustained virologic response (SVR) rates in combination with peginterferon alfa-2a–ribavirin in treatment-naive HCV genotype 1 (G1)-infected patients. This study explored the efficacy and safety of ritonavir-boosted DNV (DNVr) plus peginterferon alfa-2a–ribavirin in G1-infected prior peginterferon-ribavirin null responders. Null responders (<2-log10reduction in HCV RNA level at week 12) were given an open-label combination of 100 mg of ritonavir and 100 mg of DNV (100/100 mg DNVr) every 12 h (q12h) plus peginterferon alfa-2a–ribavirin for 12 weeks. All patients achieving an early virologic response (EVR; ≥2-log10decrease in HCV RNA by week 12) continued treatment with peginterferon alfa-2a–ribavirin; those without an EVR discontinued all study drugs. Twenty-four prior null responders were enrolled; 16 patients (67%) were infected with HCV G1b, and 8 (33%) were infected with G1a. Ninety-six percent of patients had anIL28Bnon-CC genotype. A sustained virologic response at 24 weeks posttreatment (SVR24) was achieved in 67% of patients, with a higher rate in G1b-infected (88%) than G1a-infected (25%) patients. Resistance-related breakthrough occurred in 4/8 G1a and 1/16 G1b patients through the DNV resistance-associated variant (RAV) NS3 R155K. NS3 R155K was also detected in 2/2 G1a patients who relapsed. Treatment was well tolerated. Two patients withdrew prematurely from study medications due to adverse events. Two serious adverse events were reported; both occurred after completion of DNVr therapy and were considered unrelated to treatment. No grade 3 or 4 alanine aminotransferase (ALT) elevations were observed. DNVr plus peginterferon alfa-2a–ribavirin demonstrated high SVR24 rates in HCV G1b-infected prior null responders and was well tolerated. (This study has been registered atClinicalTrials.govunder registration no. NCT01185860.)

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Efficacy and Safety of Elbasvir/Grazoprevir in Hepatitis C Virus GT1- and GT4-Infected People Aged 65 Years or Older

Gerontology and Geriatric Medicine ◽

10.1177/2333721418817398 ◽

2019 ◽

Vol 5 ◽

pp. 233372141881739 ◽

Cited By ~ 1

Author(s):

Steven Flamm ◽

Cheng-Yuan Peng ◽

Oren Shibolet ◽

Ronald Nahass ◽

Peggy Hwang ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Adverse Events ◽

Virologic Response ◽

Hcv Infection ◽

Hcv Rna ◽

Efficacy And Safety ◽

Limit Of Quantification ◽

Serious Adverse Events ◽

Infected People

Background: In elderly individuals aged ≥65 years with hepatitis C virus (HCV) infection, efficacious and safe HCV therapy is complicated by frequent comorbidities and concomitant medications. The aim of this analysis was to evaluate the efficacy and safety of elbasvir/grazoprevir (EBR/GZR) in people aged ≥65 years. Methods: This is an integrated retrospective analysis of EBR/GZR administered for 12 weeks in participants with HCV genotype 1 or 4 infection enrolled in 12 Phase 2/3 clinical trials. The primary end point was sustained virologic response 12 weeks after completing therapy (SVR12; HCV RNA below the lower limit of quantification). Results: Most participants aged ≥65 years were receiving ≥1 concomitant medication (322/339; 95.0%) and had ≥1 comorbidity (334/339; 99%). SVR12 rates were 95.3% (323/339) in participants aged ≥65 years and 95.4% (2,041/2,139) in those aged <65 years. Rates of adverse events, drug-related adverse events, serious adverse events, and discontinuations were similar in participants aged ≥65 years and those aged <65 years. In participants aged ≥65 years, median estimated glomerular filtration rate was similar at baseline and at the end of treatment. Conclusion: The efficacy and safety of EBR/GZR were similar in participants with HCV infection aged ≥65 years and those aged <65 years.

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