AMSTERDAM – Debate about whether patients taking direct-acting antiviral (DAA) therapies for hepatitis C viral (HCV) infections are at risk of developing liver cancer after achieving sustained virologic response (SVR) continued unabashed Thursday at the European Association for the Study of the Liver's (EASL) annual International Liver Congress.

Data from eight studies presented at the congress gave voice to both sides of the argument, with some suggesting that DAA therapy is associated with a higher risk of liver cancer vs. interferon (IFN)-based therapy and others finding that there is no difference in liver cancer risk after HCV is cured via either approach. In light of the uncertainty, EASL governing board member Francesco Negro said that "at this stage, there is no reason to alter treatment guidelines until the issue is definitively clarified."

A study from Spain concluded that neither of the therapeutic approaches, DAAs nor IFN-based therapy, eliminated the risk of developing liver cancer – bad news for people with HCV, who are at high risk for liver cancer, also known as hepatocellular carcinoma (HCC). The study, led by Maria Reig and Zoe Mariño, of Hospital Clinic Barcelona, Spain, in which patients with HCV and HCC who had previously been cured of HCC received DAA therapy supported concerns about the issue. After a median 12.4-month follow-up after treatment with DAAs, the rate of HCC recurrence was 31.2 percent. For those who received HCC treatment at recurrence, 30 percent of patients saw disease progression in the immediate six-month follow-up.

"These data indicate that there needs to be further research conducted in this area, clarifying the mechanism for the association between liver cancer recurrence and DAA therapy," said Reig, who was the lead author of the study.

But opposing evidence surfaced in studies from Japan and China as well as via a systematic review, meta-analyses and meta-regression study, conducted by Gregory Dore and Reem Waziry, both at the Kirby Institute at Australia's University of New South Wales, and colleagues. In 41 relevant studies encompassing nearly 14,000 patients that were included in Dore and Waziry's review, they found no evidence for higher risk of HCC occurrence or recurrence following DAA treatment, compared with IFN-based HCV therapy. After adjusting for time of study follow-up and the age of patients enrolled, they found no evidence in favor of a differential HCC occurrence or recurrence between DAA and interferon regimens.

"I try to bring things back to common sense. How would elimination of a pathogenic virus lead to a deleterious effect, sort of causing a major illness such as HCC?" Dore asked rhetorically, during a press conference held to discuss the findings. The review's findings suggested that "the higher incidence of HCC observed following DAA therapy can be explained by the shorter duration of follow-up and older age of participants, rather than the DAA treatment regimen," he said.