Direct-Acting Antivirals for HCV Reduce Mortality, Liver Cancer

The first prospective, longitudinal study of direct-acting antivirals (DAA) for hepatitis C virus (HCV) infection finds that treatment provides clinical benefit beyond virologic response, reducing risk for both all-cause mortality and for liver cancer.

Fabrice Carrat, PhD, Professor, Sorbonne Université, Institut National de la Santé et de la Récherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France, and colleagues note that, despite the success of DAA treatment in producing sustained virologic response (SVR) in HCV infections, there have been very few studies comparing clinical outcomes in treated and untreated patients.

"Although I have no doubt that SVR can be considered as a surrogate endpoint for clinical efficacy, it has not been formally demonstrated," Carrat told MD Magazine®.

A randomized clinical trial to compare treated and untreated groups is not an ethical option, nor would it be feasible to conduct a trial of sufficient length to ascertain associated clinical benefits, Carrat explained. An observational trial, however, can provide that comparison.

"To address the same issue in an observational cohort study, you compare treated versus untreated patients with careful control of potential confounding factors," Carrat said. "This is what we did in our study."

Carrat and colleagues identified 11,870 patients with chronic HCV infection seen at clinics between August 2012 and December 2015 from the prospective French ANRS Hepather cohort. Patients were excluded from the study if they had active HBV coinfection, history of hepatocellular carcinoma (HCC), decompensated cirrhosis, or had undergone liver transplantation.

The final study population comprised 9896 with a sufficient record for follow-up (median 33.4 months) to assess clinical outcomes. Approximately one-fourth of the population (n = 2551) did not receive DAA treatment and could therefore serve as a control comparison. The study primary clinical outcomes were incidence of death, HCC, and decompensated cirrhosis.

The investigators reported that the treated patients were 52% less likely to die prematurely than those who did not receive treatment, with an estimated adjusted risk in treated patients of 40 deaths in one year per 10,000 in comparison to 84 in untreated patients. Treated patients were also 33% less likely to present with HCC, with estimated adjusted risk in 1 year of 86 per 10,000 in comparison to 129 per 10,000 without treatment. DAA treatment was not associated with reduced risk of decompensated cirrhosis, however.

In an invited comment accompanying the study, Raymond Chung, MD, Director of the Liver Center, Massachusetts General Hospital, Boston, MA, and colleagues point out that previous studies have not resolved the question of whether HCC is associated with DAAs.

"The association of direct-acting antivirals with increased risk for hepatocellular carcinoma has been investigated in several single-centre reports, which have suggested an increased incidence of hepatocellular carcinoma early after direct-acting antiviral treatment," Chun and colleagues wrote. "However subsequent studies noted no association between direct-acting antivirals and increased risk for hepatocellular carcinoma—rather, they were associated with decreased risk.”

"Carrat and colleagues' findings confirm that the risk for hepatocellualar carcinoma is reduced after direct-acting antiviral treatment," Chun and colleagues declared. "These findings firmly counter those of a Cochrane review…that could neither confirm nor reject if direct-acting antivirals had an effect on long-term HCV-related morbidity and mortality."

The high tolerability and efficacy of DAA treatment in achieving SVR and this evidence of clinical benefit should be a compelling case for universal treatment, Carrat emphasized in discussing the study with MD Mag.

"Treatment of hep C with direct-acting antivirals is associated with reduced risk of mortality and liver cancer," Carrat said. "This suggests that DAAs should be considered for all patients with chronic hepatitis C infections."

The study, “Clinical Outcomes in Patients with Chronic Hepatitis C after Direct-Acting Antiviral Treatment: A Prospective Cohort Study,” was published in The Lancet.