Direct-Acting Antivirals for HCV Reduce Risk of Liver Cancer

Amanda Singer, PhD, MPH

The single leading cause of hepatocellular carcinoma (HCC) around the world is chronic infection with hepatitis C virus (HCV).

Other risk factors associated with an increased incidence of HCC include liver fibrosis, cirrhosis, increased age, male sex, diabetes, obesity, smoking, excessive alcohol intake, hepatitis B virus (HBV) co-infection, and HCV genotype 3 infection.

Prior to the recent availability of direct-acting antivirals (DAAs) for the treatment of HCV, interferons were a mainstay of therapy. Evidence suggests that interferon-based therapy to achieve sustained virologic response (SVR) in patients with chronic HCV dramatically reduces the risk of HCC, although it may take many years to fully realize that risk reduction.

Recent studies have reached disparate conclusions regarding the impact of DAAs on the risk of HCC among patients with HCV who have achieved SVR. As a result, Gilead Sciences, Inc., a biopharmaceutical company responsible for bringing a number of DAAs to the market, funded an investigation to further elucidate the relationship between DAAs and the risk of HCC.

Amanda Singer, PhD, MPH, researcher at Gilead and lead study author, and colleagues explained the rationale for their investigation, “The seriousness of HCC as a potential treatment-related outcome, contrasted with the serious implications of withholding HCV treatment from sick patients due to a potentially unfounded concern of an increased risk of HCC development after DAA therapy, warrants further investigation.”

This retrospective observational cohort study used a database that included de-identified pharmacy and medical data for over 100 million patient-lives. Patients were included in the study if they were 18 years or older with HCV, based on ICD-9 and ICD-10 codes for HCV or prescriptions for HCV, treated with a DAA-based regimen.

For comparison, investigators also examined a group of patients with untreated HCV and a group of patients with HCV treated with an interferon-based regimen. They additionally collected baseline characteristics, including age and sex, for all patients.

The DAA-treated group consisted of 30,183 patients, compared with 137,502 patients in the untreated group and 12,948 patients in the interferon-treated group. Without accounting for baseline characteristics, the incidence rates of liver cancer were higher among patients in the DAA-treated group when compared with both the untreated group and the interferon-treated group.

Once adjustments were made for age, sex, and baseline medical conditions (including cirrhosis, portal hypertension, and thrombocytopenia), the results showed a reduced risk of liver cancer among patients treated with DAAs when compared with both untreated patients and patients treated with interferons.

Singer and colleagues offered their reasoning for adjusting for baseline characteristics as part of their analysis, “At baseline, DAA-treated patients had a higher prevalence of independent risk factors for liver cancer (including older age, male gender, and advanced liver disease) compared with untreated and interferon-treated HCV patients.”

The authors also pointed out that a number of other studies that found an increased risk of HCC among patients with HCV treated with DAAs did not account for these baseline differences.

The study authors acknowledged that it is still too early to determine the long-term impact of DAAs on the risk of liver cancer, noting, “As patients cured of their HCV infection through treatment with DAAs are followed for longer periods of time, the true benefit of these medications in improvement of patient health, both from hepatic as well as extra-hepatic complications, will become more apparent.”

The study, “Direct-acting antiviral treatment for hepatitis C virus infection and risk of incident liver cancer: a retrospective cohort study,” was published online ahead of print this month in Alimentary Pharmacology and Therapeutics.