Glecaprevir, Pibrentasvir Effective for HCV Regardless of Cirrhosis, Treatment Period

Credit: Adobe Stock

Findings from a recent study suggest glecaprevir/pibrentasvir therapy is effective for patients with cirrhosis with chronic hepatitis C virus (HCV) infection, regardless of whether they undergo an 8 or 12-week treatment period.¹

Results showed glecaprevir/pibrentasvir was highly efficacious regardless of fibrosis status and treatment period with an overall sustained virological response (SVR) rate of 99% in a cohort of more than 1000 patients across 24 centers in Japan. This finding was consistent across patients with cirrhosis who received 8 weeks of treatment, as opposed to 12.¹

“In clinical practice, liver fibrosis may be difficult to assess accurately, and an appropriate treatment period may not be selected,” Namiki Izumi, MD, PhD, of Musashino Red Cross Hospital in Japan, and colleagues wrote.¹ “Specifically, whether 8 weeks of treatment for cirrhosis may reduce treatment efficacy has not been adequately investigated.”

Although DAA therapy can cure more than 95% of HCV infections and treatment duration is generally short, the World Health Organization cites cirrhosis as an important consideration when assessing the appropriate treatment period for a patient with chronic hepatitis C.² Liver biopsy is the gold standard for assessing fibrosis, but the invasive nature of this test hinders its feasibility in clinical practice, potentially posing important implications for patients who may have cirrhosis and require an altered DAA treatment period.³

To address this gap in research, investigators conducted a prospective, nationwide, multicenter cohort study of patients with chronic HCV who received glecaprevir/pibrentasvir therapy at 24 participating sites across Japan from November 2017 - January 2019. Investigators noted patients with decompensated cirrhosis were excluded due to glecaprevir/pibrentasvir not being approved for this patient population in Japan. Additionally, they excluded patients with a previous history of DAA therapy, patients who were not evaluated for SVR after 12 weeks of treatment, and patients who were lost to follow-up or did not complete treatment.¹

In total, 1275 patients with chronic HCV were included in the study. Patients were assigned 8 or 12-week treatment periods by their physicians. Apart from the clinical diagnoses made by each physician, liver fibrosis was assessed retrospectively using the fibrosis-4 (FIB-4) index, with FIB-4 >3.25 serving as the threshold of cirrhosis. The primary endpoint was the SVR rate in patients with chronic hepatitis and cirrhosis.¹

Among the cohort, the median age was 66 years and 54.3% of patients were female, 5.8% of whom had a history of hepatocellular carcinoma (HCC). In all patients, the SVR rate of glecaprevir/pibrentasvir therapy was 99.1%. Investigators noted SVR did not significantly differ based on patients’ genotype (P = .06).¹

Additionally, they noted rates of SVR were not statistically significantly different between patients with chronic hepatitis with 8 weeks of treatment (98.9%), chronic hepatitis with 12 weeks of treatment (100%), cirrhosis with 8 weeks of treatment (100%), and cirrhosis with 12 weeks of treatment (99.1%; P = 0.4).¹

Investigators highlighted multiple limitations to these findings, including the use of FIB-4 to determine the presence of cirrhosis, potential selection bias from physicians regarding treatment periods, and the possibility of non-cirrhosis cases being mislabeled.¹

“In this study, GLE/PIB therapy had high efficacy regardless of liver fibrosis status and treatment periods, and even patients with cirrhosis and 8 weeks of treatment achieved high SVR rates,” investigators concluded.¹

References:

1. Morita A, Tamaki N, Kobashi H, et al. Effect of treatment periods on efficacy of glecaprevir and pibrentasvir in chronic hepatitis C: A nationwide, prospective, multicenter study. JGH Open. 2024;8(4):e13068. doi:10.1002/jgh3.13068
2. World Health Organization. Hepatitis C. Newroom. April 9, 2024. Accessed May 10, 2024. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c
3. American Liver Foundation. Fibrosis (Scarring). About Your Liver. September 6, 2023. Accessed May 20, 2024. https://liverfoundation.org/about-your-liver/how-liver-diseases-progress/fibrosis-scarring/