Hepatitis C Genotype, Cirrhosis, Gender May Impact Effectiveness of DAA Therapy

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Although the overall response rate among the cohort was 96.4%, this figure dropped as low as 66.7% when accounting for male gender, GT3 infection, cirrhosis, obesity, and non-response to previous therapy.

Treatment-experienced men with cirrhosis and obesity infected with hepatitis C virus (HCV) genotype 3 (GT3) may be susceptible to reduced treatment efficacy for pan-genotypic direct-acting antiviral (DAA) therapy, according to findings from a recent study.

Although the overall response rate to the sofosbuvir/velpatasvir was 96.4% among the cohort, male gender, genotype 3 infection, cirrhosis, obesity, and non-response to previous therapy were shown to negatively impact the odds of cure, reducing this figure to as low as 66.7%.1

Although the World Health Organization estimates DAAs are able to cure more than 95% of the 58 million cases of HCV worldwide, access to diagnosis and treatment remains low and continues to inhibit disease management and eradication efforts. However, other clinical factors may play a role in determining the curative power of DAAs and can aid clinicians’ ability to treat patients and best predict outcomes in those who may not respond to therapy. Thus, a comprehensive understanding of these influences will be critical.2

“These difficulties have been overcome in the era of DAA drugs, especially with the introduction of highly potent pangenotypic regimens, but still, a success rate of more than 95% does not mean that every patient will be cured,” wrote investigators.1 “And although the scale of failure is incomparably smaller than in the case of interferon-based therapies, knowledge about the factors that reduce the chances of recovery is extremely important, even for the strategy of planning rescue therapy.”

To identify negative predictors reducing the odds of successful pangenotypic sofosbuvir/velpatasvir therapy, Robert Flisiak, MD, PhD, head of the department of infectious diseases and hepatology at the Medical University of Bialystok in Poland, and colleagues retrospectively collected clinical and laboratory data for patients from the EpiTer-2 database and assessed the effectiveness of therapy for inducing a cure in different patient populations. A retrospective, multicenter, real-world study examining DAA treatment in patients with HCV, EpiTer-2 involves 17,166 patients with HCV from 22 hepatology centers in Poland.1

Investigators identified a total of 5549 patients from EpiTer-2 who were treated with pangenotypic regimens. After excluding those lost to follow-up, the population was limited to 5355 patients, which included 2267 treated with sofosbuvir/velpatasvir and the possible addition of ribavirin. Of those patients, 92% received sofosbuvir/velpatasvir-based treatment for 12 weeks and 7.1% had ribavirin added to their regimen.1

The majority of patients in the analyzed group were men (57.6%) and the median age was 50 years (Interquartile range [IQR], 40-60). Infection with GT1 (60.3%) and and GT3 (30.1%) were most common among the cohort, and advanced liver disease (F3 or F4) was diagnosed in 43% of patients.1

Investigators assessed the effectiveness of treatment in the Intent to Treat (ITT) analysis, which included patients who received ≥ 1 dose of antiviral. However, they noted their primary focus was on the per-protocol (PP) analysis established by excluding patients with non-virologic failure.1

Among patients with GT3 (n = 646), the cure rate was 93.5%. In the 421 patients with body mass index (BMI) > 30, 94.1% were cured. This figure was further reduced among 635 patients with cirrhosis (92.3%) but increased slightly to 95.5% in a population of 1233 men. Patients demonstrating previous non-response to treatment (n = 214) exhibited a cure rate of 89.7%.1

Investigators noted patients with a combination of these worsening factors accounted for approximately 2.6% of the cohort. An analysis of a group of 60 cirrhotic and obese patients infected with HCV GT3 showed 85% effectiveness of sofosbuvir/velpatasvir with ribavirin. However, after limiting this group to men only (n = 43), this figure decreased to 79.1% and reached a lowest 66.7% cure rate after taking into account non-responders to previous therapies.1

“Despite a high overall cure rate exceeding 96%, we demonstrated a relatively low effectiveness of therapy in treatment-experienced men with obesity and cirrhosis infected with GT3. In this small, because constituting less than 2.6% of the population ‘difficult to cure’ patient population, triple pangenotypic therapy should be considered as first-line management, which needs to be confirmed in further studies,” investigators concluded.1


  1. Flisiak R, Zarębska-Michaluk D, Berak H, et al. Treatment with Sofosbuvir/Velpatasvir of the most difficult to cure HCV-infected population. Pol Arch Intern Med. doi:10.20452/pamw.16644
  2. World Health Organization. Hepatitis C. Newsroom. July 18, 2023. Accessed January 11, 2024.