Dr Jacinta Holmes

Evidence from a real world cohort of patients with hepatitis C treated with direct acting antivirals has countered the findings of a Cochrane Review that claimed the drugs did not reduce morbidity or mortality.

Findings from a multicentre French study that followed up more than 10,000 adult patients with chronic HCV for three years showed that DAA treatment was associated with a 50% reduction in all cause mortality and 33% reduction in hepatocellular carcinoma.

Published in The Lancet, the study reported outcomes at a mean of 33 months for 7,344 people treated with DAAs and 2,551 who were untreated.

Findings of adjusted multivariable analyses showed that exposure to DAAs significantly reduced all-cause mortality (84 vs 40 deaths per 10,000 patients/year for untreated vs treated patients, Hazard Ratio 0·48).

Significant reductions were also seen for liver-related mortality (HR 0·39), non-liver-related mortality (HR 0·60), and hepatocellular carcinoma (129 vs 86/10,000 patients, HR 0·66), but not decompensated cirrhosis (HR 1·14).

The reductions in mortality and morbidity were stronger when the analysis was restricted to patients with cirrhosis who achieved a sustained virological response (SVR).

There was an increased risk of hepatocellular carcinoma (HR 2.23) in the 5% of patients who failed to achieve SVR.

However the study authors said that overall, the findings were likely to have underestimated the potential benefits of DAAs because the study excluded patients with a history of decompensated cirrhosis and liver transplantation.

They noted that for ethical reasons it was not possible to conduct a trial with an untreated control arm to confirm the findings.

“Nevertheless, our results support urgent treatment of patients with advanced liver disease and extension of the follow-up of treated patients with less severe disease to assess the long-term clinical effect of direct-acting antiviral treatment,” they wrote.

An accompanying commentary in the Lancet, co-authored by Dr Jacinta Holmes of the Department of Gastroenterology, St Vincent’s Hospital, Melbourne, said the trial offered substantive evidence that cure of HCV with DAAs 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,” it said.

“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.”

In 2017 GESA strongly rejected the conclusions of Cochrane authors, who said their systematic review showed it was questionable whether eradication of HCV with DAAs led to improved survival and fewer complications.