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DAA therapy regardless of SVR reduces hepatic, extrahepatic mortality

Results of a prospective study showed that treatment with direct-acting antivirals for hepatitis C correlated with significantly reduced risks for hepatocellular carcinoma and mortality, according to a study published in The Lancet.

“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,” Fabrice Carrat, MD, PhD, from Sorbonne University in France, and lead study author, said in a press release.

Carrat and colleagues reviewed the data and follow-up data of 9,895 initially untreated patients with HCV who had been recruited to the ANRS CO22 Hepather cohort between Aug. 6, 2012, and Dec. 31, 2015. Median follow-up from recruitment to post-DAA treatment was 33.4 months.

During follow-up, 218 patients died including 73 liver-related deaths. The researchers also reported 258 cases of HCC and 106 cases of decompensated cirrhosis. Twenty-five patients underwent liver transplantation.

Multivariate analysis showed that exposure to DAAs correlated with a decreased risk for all-cause mortality (HR = 0.48; 95% CI, 0.33-0.7), liver-related death (HR = 0.39; 95% CI, 0.21-0.71), non-liver-related death (HR = 0.6; 95% CI, 0.36-1), and HCC (HR = 0.66; 95% CI, 0.46-0.93).

The sustained virologic response rate was 94% after excluding patients who were lost to follow-up or outcome was otherwise unknown.

“A striking finding in our study was the lower risk for non-liver-related mortality in patients treated with direct-acting antivirals compared with untreated patients,” Carrat and colleagues wrote. “Although a decrease in long-term non-liver-related mortality has been reported in patients with sustained virological response compared with those without a sustained virological response after interferon-based therapy, reverse causality could be another possibility if patients with the most severe liver disease and the highest risk for death from any cause had a lower probability of starting direct-acting antiviral treatment.”

Results from a further multivariate analysis comparing treated patients with untreated patients, SVR correlated with a significant decrease in all-cause mortality, liver-related mortality, non-liver-related mortality and HCC. In contrast, not achieving SVR correlated with a significant increase in the risk for HCC (HR = 2.23; 95% CI, 1.37-3.64).

“Direct-acting antivirals induce a sustained virological response, reducing liver damage and inflammation. This eect causes liver regeneration, decreasing risk for progression to liver-related complications or hepatocellular carcinoma,” the researchers concluded. – by Talitha Bennett

Disclosure: Carrat reports grants from INSERM-ANRS during the conduct of the study. Please see the full study for the other authors’ relevant financial disclosures.