PMID- 32621971 OWN - NLM STAT- MEDLINE DCOM- 20210818 LR - 20220531 IS - 1542-7714 (Electronic) IS - 1542-3565 (Linking) VI - 18 IP - 11 DP - 2020 Oct TI - Eight Weeks of Treatment With Glecaprevir/Pibrentasvir Is Safe and Efficacious in an Integrated Analysis of Treatment-Naive Patients With Hepatitis C Virus Infection. PG - 2544-2553.e6 LID - S1542-3565(20)30907-1 [pii] LID - 10.1016/j.cgh.2020.06.044 [doi] AB - BACKGROUND & AIMS: The direct-acting antiviral combination glecaprevir/pibrentasvir has been approved by the Food and Drug Administration for 8 weeks of treatment in treatment-naive patients with hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis. We performed an integrated analysis of data from trials to evaluate the overall efficacy and safety of 8 weeks of glecaprevir/pibrentasvir in treatment-naive patients without cirrhosis or with compensated cirrhosis. METHODS: We pooled data from 8 phase 2 or phase 3 trials of treatment-naive patients with HCV genotype 1 to 6 infections, without cirrhosis or with compensated cirrhosis, who received 8 weeks of glecaprevir/pibrentasvir. RESULTS: Of 1248 patients, 343 (27%) had cirrhosis. Most patients were white (80%) and had HCV genotype 1 infection (47%) or genotype 3 infection (22%); the median age was 54 years. Overall rates of sustained virologic response at post-treatment week 12 were 97.6% (1218 of 1248) in the intention to treat (ITT) and 99.3% (1218 of 1226) in the modified ITT populations. When we excluded patients with genotype 3 infections with compensated cirrhosis (consistent with the European label), rates of sustained virologic response at post-treatment week 12 were 97.6% in the ITT and 99.4% in the modified ITT populations. Eight virologic failures (7 in patients without cirrhosis and 1 in a patient with cirrhosis) occurred in the ITT population. Virologic failure was not associated with markers of advanced liver disease or populations of interest (current alcohol use, opioid substitution therapy, history of injection-drug use, and severe renal impairment). Treatment-emergent adverse events (AEs) occurred in 58% of patients. The most frequent AEs (>10%) were headache (12%) and fatigue (12%). Serious AEs and AEs that led to glecaprevir/pibrentasvir discontinuation were reported in 2% and less than 1% of patients, respectively. CONCLUSIONS: In a pooled analysis of data from 8 trials, we found that 8 weeks of treatment with glecaprevir/pibrentasvir is efficacious and well tolerated in treatment-naive patients with HCV genotype 1 to 6 infections, with or without cirrhosis. CI - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Zuckerman, Eli AU - Zuckerman E AD - Liver Unit, Carmel Medical Center, Faculty of Medicine, Technion Institute, Haifa, Israel. Electronic address: elizuc56@gmail.com. FAU - Gutierrez, Julio A AU - Gutierrez JA AD - Scripps Clinic, Center for Organ and Cell Transplantation, La Jolla, California. FAU - Dylla, Douglas E AU - Dylla DE AD - AbbVie, Inc, North Chicago, Illinois. FAU - de Ledinghen, Victor AU - de Ledinghen V AD - Centre d'Investigation de la Fibrose Hepatique, Bordeaux University Hospital, Pessac, France; INSERM U1053, Bordeaux University, Bordeaux, France. FAU - Muir, Andrew J AU - Muir AJ AD - Duke Clinical Research Institute, Durham, North Carolina. FAU - Gschwantler, Michael AU - Gschwantler M AD - Department of Internal Medicine IV, Wilhelminenspital, Vienna, Austria; Sigmund Freud University, Vienna, Austria. FAU - Puoti, Massimo AU - Puoti M AD - Niguarda ca Grande Hospital, Milan, Italy. FAU - Caruntu, Florin AU - Caruntu F AD - National Institute for Infectious Diseases "Prof. Matei Bals," Bucharest, Romania. FAU - Slim, Jihad AU - Slim J AD - Infectious Disease Division, Department of Internal Medicine, St. Michael's Medical Center, Newark, New Jersey. FAU - Nevens, Frederik AU - Nevens F AD - Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Belgium. FAU - Sigal, Samuel AU - Sigal S AD - Montefiore Medical Center, Bronx, New York. FAU - Cohen, Stanley AU - Cohen S AD - UH Cleveland Medical Center, Cleveland, Ohio. FAU - Fredrick, Linda M AU - Fredrick LM AD - AbbVie, Inc, North Chicago, Illinois. FAU - Pires Dos Santos, Ana Gabriela AU - Pires Dos Santos AG AD - AbbVie, Inc, North Chicago, Illinois. FAU - Rodrigues, Lino Jr AU - Rodrigues L Jr AD - AbbVie, Inc, North Chicago, Illinois. FAU - Dillon, John F AU - Dillon JF AD - Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, United Kingdom. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't DEP - 20200701 PL - United States TA - Clin Gastroenterol Hepatol JT - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association JID - 101160775 RN - 0 (Aminoisobutyric Acids) RN - 0 (Antiviral Agents) RN - 0 (Benzimidazoles) RN - 0 (Cyclopropanes) RN - 0 (Lactams, Macrocyclic) RN - 0 (Pyrrolidines) RN - 0 (Quinoxalines) RN - 0 (Sulfonamides) RN - 2WU922TK3L (pibrentasvir) RN - 9DLQ4CIU6V (Proline) RN - GMW67QNF9C (Leucine) RN - K6BUU8J72P (glecaprevir) SB - IM MH - Aminoisobutyric Acids MH - Antiviral Agents/adverse effects MH - Benzimidazoles MH - Cyclopropanes MH - Genotype MH - Hepacivirus/genetics MH - *Hepatitis C/drug therapy MH - *Hepatitis C, Chronic/complications/drug therapy MH - Humans MH - Lactams, Macrocyclic MH - Leucine/analogs & derivatives MH - Middle Aged MH - Proline/analogs & derivatives MH - Pyrrolidines MH - Quinoxalines MH - Sulfonamides OTO - NOTNLM OT - DAA OT - Fibrosis OT - Liver OT - Panfibrotic OT - Pangenotypic EDAT- 2020/07/06 06:00 MHDA- 2021/08/19 06:00 CRDT- 2020/07/05 06:00 PHST- 2020/03/11 00:00 [received] PHST- 2020/05/06 00:00 [revised] PHST- 2020/06/08 00:00 [accepted] PHST- 2020/07/06 06:00 [pubmed] PHST- 2021/08/19 06:00 [medline] PHST- 2020/07/05 06:00 [entrez] AID - S1542-3565(20)30907-1 [pii] AID - 10.1016/j.cgh.2020.06.044 [doi] PST - ppublish SO - Clin Gastroenterol Hepatol. 2020 Oct;18(11):2544-2553.e6. doi: 10.1016/j.cgh.2020.06.044. Epub 2020 Jul 1.