Direct-Acting Antivirals Lower All-Cause Mortality in Chronic HCV Infection

hepatocellular carcinoma
hepatocellular carcinoma
Researchers compared the prevalence of death, hepatocellular carcinoma, and decompensated cirrhosis between patients treated with direct-acting antivirals and patients not treated.

For patients with chronic hepatitis C virus (HCV) infection, treatment with direct-acting antivirals reduces the risk for all-cause mortality and hepatocellular carcinoma (HCC), according to results published in the Lancet.

The study included adult participants with chronic HCV infection from 32 hepatology centers in France. Participants were excluded if they had chronic hepatitis B, a history of decompensated cirrhosis, a history of HCC, a history of liver transplantation, and participants treated with interferon-ribavirin with/without first-generation protease inhibitors.

The coprimary outcomes were incidence of all-cause mortality, HCC, and decompensated cirrhosis. The researchers used Cox proportional hazard models to determine associations between direct-acting antivirals and the study outcomes.

In total, the study included 9895 participants with a median follow-up time of 33.4 months. During the follow-up period, 7344 participants initiated treatment with direct-acting antivirals, whereas 2551 remained untreated as of their final follow-up visit.

During follow-up, 218 participants died (129 treated and 89 untreated), 258 reported HCC (187 treated and 71 untreated), and 106 had decompensated cirrhosis (74 treated and 32 untreated).

The researchers then adjusted for variables including age, sex, body mass index, geographical origin, infection route, fibrosis score, HCV treatment naivety, HCV genotype, alcohol consumption, diabetes, arterial hypertension, biological variables, and model for end-stage liver disease score in participants with cirrhosis. They found that exposure to direct-acting antivirals was associated with a decrease in both all-cause mortality (adjusted hazard ratio [aHR], 0.48; 95% CI, 0.33-0.70) and HCC (aHR 0.66; 95% CI, 0.46-0.93). It was not associated with decompensated cirrhosis (aHR 1.14; 95% CI, 0.57-2.27).

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“To our knowledge, the [French National Research Agency] CO22 Hepather cohort study is the first prospective longitudinal study to investigate clinical outcomes associated with direct-acting antiviral treatment in patients with chronic HCV infection, by comparing patients treated with direct-acting antivirals with those untreated with these drugs, irrespective of the status of sustained virological response, with careful control of confounding and indication biases,” the researchers wrote.


Carrat F, Fontaine H, Dorival C, et al. Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: a prospective cohort study [published online February 11, 2019]. Lancet. doi: 10.1016/S0140-6736(18)32111-1