Direct-acting antivirals are associated with reduced risk of mortality and liver cancer, according to results from the first prospective, longitudinal study investigating their use in treating chronic hepatitis C
The research, published in The Lancet, is the first to demonstrate the clinical effectiveness of DAAs on the disease. It suggests that they should be considered for all patients with chronic hepatitis C infection, the authors say.
They compared the incidence of death, hepatocellular carcinoma, and decompensated cirrhosis between patients treated with DAAs and those untreated, in the French ANRS CO22 Hepather cohort.
Because ethics precluded setting up a trial with a control group, the researchers set up an observational study with 10,166 patients eligible between August 2012 and December 2015.
They excluded patients excluded patients with a history of decompensated cirrhosis and liver transplantation, saying that the potential benefits of treatment in this group could be underestimated because of their exclusion, as trial data shows improvements in liver function in patients with decompensated cirrhosis who achieved a sustained virological response.
Of the more than 10,000 eligible patients, 9,895 (97%) had available follow-up information and were included in the analyses.
“Median follow-up was 33.4 months (IQR 24.0–40.7),” they wrote.
“Treatment with direct-acting antivirals was initiated during follow-up in 7,344 patients, and 2,551 patients remained untreated at the final follow-up visit.
“During follow-up, 218 patients died (129 treated, 89 untreated), 258 reported hepatocellular carcinoma (187 treated, 71 untreated), and 106 had decompensated cirrhosis (74 treated, 32 untreated).
“Exposure to direct-acting antivirals was associated with increased risk for hepatocellular carcinoma (unadjusted hazard ratio [HR] 2.77, 95% CI 2.07–3·71) and decompensated cirrhosis (3.83, 2.29–6.42).
“After adjustment for variables (age, sex, body-mass index, geographical origin, infection route, fibrosis score, HCV treatment-naive, HCV genotype, alcohol consumption, diabetes, arterial hypertension, biological variables, and model for end-stage liver disease score in patients with cirrhosis), exposure to direct-acting antivirals was associated with a decrease in all-cause mortality (adjusted HR 0.48, 95% CI 0.33–0.70) and hepatocellular carcinoma (0.66, 0.46–0.93), and was not associated with decompensated cirrhosis (1.14, 0.57–2.27).
“Taking a large cohort like this provides the opportunity to evaluate the effect of direct-acting antiviral therapy on the long-term outcomes of patients with hepatitis C,” said Professor Fabrice Carrat of the Sorbonne Université, France.
“We saw a reduction of risk for complications related to the disease, and to mortality, and believe this treatment should be considered for all patients with chronic hepatitis C infection.”
“Writing in a linked Comment, Dr Raymond T Chung, Director of the Liver Center at Massachusetts General Hospital, USA, says: “The study by Carrat and colleagues offers substantive evidence that cure of HCV delivered by all-oral direct-acting antiviral regimens is associated with clinical benefits”.
“These findings firmly counter those of a Cochrane review of direct-acting antiviral treatment trials that could neither confirm nor reject if direct-acting antivirals had an effect on long-term HCV-related morbidity and mortality.
“They also provide the best evidence to date to support guidance documents that recommend direct-acting antiviral treatment for all patients with chronic HCV infection. Finally, they provide credence to the achievability of the goals set out by WHO, not only to eliminate HCV but also to substantially reduce its complications.”