Elbasvir-Grazoprevir Zepatier
Glecaprevir-Pibrentasvir Mavyret
Ledipasvir-Sofosbuvir Harvoni
Ribavirin Copegus, Rebetol, Ribasphere
Sofosbuvir Sovaldi
Sofosbuvir-Velpatasvir Epclusa
Sofosbuvir-Velpatasvir-Voxilaprevir VoseviDuration of glecaprevir-pibrentasvir in compensated cirrhosis
Clinical Challenge
What duration of therapy would you recommend?
Expert Opinions
Charles Landis, MD, PhD
Associate Professor of Medicine
Division of Gastroenterology
University of Washington
The patient should be sent for an HCC screening ultrasound (US) prior to starting any treatment.
Current AASLD/IDSA guidelines recommend 8 weeks of glecaprevir-pibrentasvir (G/P) for patients with compensated cirrhosis and genotype 3. The recommendation is based on findings from the EXPEDITION-8 study which evaluated 8 weeks of G/P in 343 patients with GT1-6 and compensated cirrhosis. Overall, 98% of the entire cohort achieved an SVR12. In a subgroup of in 63 patients with genotype 3 (n=63), 95% achieved SVR12 (60/63). Of the 3 treatment failures, one was virologic failure (relapse) and 2 were lost to follow-up (per-protocol SVR 98%). Subsequent real world studies have found similar SVRs rates for this group. Some clinicians are reluctant to embrace an 8 week treatment duration, citing limited data and modestly reduced SVR rates. Faced with the available data, treatment with 8 weeks of therapy appears adequate. Assuming that this patient's US does not identify an HCC or ascites, I would offer 8 weeks of G/P, per current AASLD/IDSA guidelines.
- Brown RS Jr, Buti M, Rodrigues L, et al. Glecaprevir/pibrentasvir for 8 weeks in treatment-naïve patients with chronic HCV genotypes 1-6 and compensated cirrhosis: The EXPEDITION-8 trial. J Hepatol. 2020;72:441-9.[PubMed Abstract] -
- Cornberg M, Ahumada A, Aghemo A, et al. Safety and Effectiveness Using 8 Weeks of Glecaprevir/Pibrentasvir in HCV-Infected Treatment-Naïve Patients with Compensated Cirrhosis: The CREST Study. Adv Ther. 2022 May 11.[PubMed Abstract] -
Medical Director
Laura Rodriguez Research Institute
Chief, Population Health
Director, Graduate Medical Education
Family Health Centers of San Diego
Grants: Gilead Sciences
Speaker's Fee: Abbvie, Gilead Sciences, Janssen, Merck
Because this patient is treatment naive, HIV-negative, CTP of 5 and without any known decompensating events, the correct duration of treatment is 8 weeks of Glecaprevir-Pibrentasvir. This is in line with AASLD/IDSA guideline recommendations and is based on the EXPEDITION-8 trial, a single-arm, multi-center, phase IIIb trial of Glecaprevir/Pibrentasvir in N = 343 patients with compensated cirrhosis. SVR12 rate overall in patients with compensated cirrhosis was 99.7% (334/335) in the per protocol population and 97.7% (335/343) in the intention to treat population.
Specifically with respect to GT-3 cirrhotic patients, in EXPEDITION-8 there were 63 patients with GT-3 of which only one had a virologic failure and two were lost to follow-up, yielding a per protocol SVR12 rate of 95% (60-63). It should be noted that HIV and HBV co-infected patients, and those with HCC and decomensated cirrhosis were excluded, and that Glecaprevir/Pibrentasvir is in fact contraindicated in patients with decompensated cirrhosis as there have been reports of worsening hepatic function and precipitated decompensation in patients treated with HCV protease inhibitors.