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WASHINGTON -- Analysis of America's veterans might have closed the books on a controversy over modern hepatitis C (HCV) treatment.

In the largest cohort analyzed to date -- some 62,000 patients in the VA system -- there is no evidence that therapy with newer agents that act directly against the virus (DAAs) increases the risk of hepatocellular carcinoma (HCC), according to George Ioannou, BMBCh, of the Veterans Affairs Puget Sound Health Care System in Seattle.

In fact, curing HCV with the DAAs is associated with a 71% reduction in the risk of HCC -- much the same picture seen after a cure with earlier regimens, Ioannou told reporters at the Liver Meeting, the annual conference of the.

The issue has been controversial. In 2016, Italian researchers reported that they had found that cirrhotic patients treated with DAAs had sharply higher-than-expected rates of HCC after they were cured of HCV.

Earlier this year, other studies appeared to show the finding was incorrect but experts said the case was not quite closed and suggested more research was needed.

The findings had made some physicians and patients less eager to use the new agents, which had appeared to deliver cures with "no downside," Ioannou said.

But the VA study, and other research with similar outcomes, appears to have settled the question, Ioannou told 番茄社区app. "I am more relaxed," he said.

Indeed, the issue of some mysterious effect of the DAAs that increases the risk of new cancers "has been put to rest," commented Norah Terrault, MD, of the University of California San Francisco, who was not part of the study, but who moderated the media briefing at which details were presented.

Terrault said the apparent increase in HCC risk was probably seen because the physicians were treating sicker patients with the DAAs, patients who would not have been eligible for the more toxic and arduous earlier regimens.

"The beauty of the VA database is that you have so much power to account for all the potential confounders" and come up with an accurate estimate of risk, she said. She cautioned there is still some question about what effect DAAs have on recurrence of HCC after treatment, but that too, she said, can likely be addressed by the VA database.

Ioannou and colleagues looked at 62,354 vets with HCV who started antiviral therapy between 1999 and the end of 2015. A majority of those were treated with the older interferon-based regimens, and some with a combination of DAAs and interferon, but 21,948 were treated with DAAs alone.

Through June 15 this year -- with an average follow-up of 6.1 years -- those patients had 3,271 incident liver cancers.

Analysis found:

• Patients who were cured, regardless of the method, had a lower risk of liver cancer than those who failed therapy.
• The risk reduction was 50% if the patients had cirrhosis and 68% if not.
• Compared with those whose weren't cured, successful interferon therapy led to a 68% risk reduction, while successful DAA treatment reduced the risk by 71%. (The combination therapies had a lower benefit at 52%.)
• The type of antiviral regimen was not associated with HCC incidence.

Ioannou cautioned that the study only examined new cases of HCC, not recurrent disease, and did not include a "no treatment" control group. He added that the relationship between HCV cure and reduced cancer risk might not be causal.

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