Conflicting Evidence Surfaces on Anti-HCV Drugs for Liver Cancer

A new generation of drugs has proved highly effective against the hepatitis C virus but there is conflicting evidence about whether the therapies promote cancer recurrence in infected patients with hepatocellular carcinoma who already have responded to curative treatment.

María Reig, MD

A new generation of drugs has proved highly effective against the hepatitis C virus (HCV), a leading risk factor for liver cancer in the United States, but there is conflicting evidence about whether the therapies promote cancer recurrence in infected patients with hepatocellular carcinoma (HCC) who already have responded to curative treatment.

Researchers who have been at the forefront of studying this unexpected controversy concerning direct-acting antiviral (DAA) treatments for HCV presented their findings at the 2016 International Liver Cancer Association (ILCA) conference in Vancouver, Canada.

María Reig, MD, of the Barcelona Clinic Liver Cancer (BCLC) Group, reported that 27.6% of 58 patients who had achieved a complete response and lacked non-characterized nodules after curative HCC therapy and went on to take the anti-HCV drugs experienced a recurrence of their cancer after a median follow-up of 5.7 months. The incidence was higher if broader groups of patients who had been treated with HCC were considered, Reig indicated.

Notably, the recurrence rates were higher and surfaced earlier than has been shown in other cohorts of patients who have responded to various HCC treatments, Reig said.

By contrast, no evidence of an increased risk of recurrence was found by researchers who culled through findings from 3 French prospective multicenter trials of 660 patients with chronic HCV or cirrhosis who were treated for HCC. Of these patients, 516 received DAA therapy after their cancer treatment.2

In one group of patients with chronic HCV who responded to HCC therapy, the rate of HCC recurrence was 12.7% among 189 patients who received posttreatment DAA drugs versus 20.5% among 78 patients who did not. In the largest study, the rate of recurrence among liver transplant patients after DAA therapy was 2.2%.2

The controversy, which has been brewing since the BCLC findings1 were initially reported in April, has helped spark a review of the class of HCV drugs by the European Medicines Agency (EMA).3

The agency said it began evaluating the DAA therapies in March after reports that the drugs triggered a reactivation of hepatitis B in patients who had been infected with the hepatitis B and C viruses. The scope of the review was expanded to include the risk of HCC recurrence after DAA therapy as a result of the BCLC report, the EMA said.3

The FDA has approved approximately 6 new drugs or regimens in the DAA class since 2013, when the approval of the first such medication signaled a major advance in the treatment of HCV. DAA therapies are interferon-free regimens that have demonstrated rates of sustained virological responses in 95% to 97% in patients with compensated cirrhosis and 85% to 90% in patients with more advanced liver disease.1

Jordi Bruix, MD

“With the new antivirals, it was supposed that we would find a reduction in the development of cancer in patients who have not had such disease and also that we would better control the liver function and the potential development of new cancer in the patients who have been treated and cured of cancer,” said Jordi Bruix, MD, PhD, director of the BCLC Group, in an interview with OncLive at ILCA.

“What we detected in Barcelona was that we had an unexpected high rate of recurrence of cancer in patients who were free of the disease after being treated in a timeframe that was quite close to their treatment with new antivirals,” he said.

Bruix said his group’s findings were raised as “a note of caution” about the impact of the DAA therapies in patients with HCC and that further study is needed. Pivotal trials of the new generation HCV drugs did not include patients with cancer, including HCC, as is typical in such studies, Bruix noted.

A likely reason for HCC recurrence in patients who have responded to treatment may be due to the impact on the immune system of the anti-viral medications, which achieve rapid reductions in the viral load, Bruix said.

“This probably shakes the relationship with inflammation and immune activation,” he said. “It may be that what we have at that point is a reduction of the immune surveillance and that clones that were dormant are able to be awakened and grow.”

He said a similar phenomenon has been seen in other cancers; for example, patients with breast cancer can be free of disease but harbor malignant cells in their bone marrow. “The cells are there but they do not grow because the immune control maintains everything in place,” he said.

“We need to have more data properly analyzed with the populations fully defined,” said Bruix, adding that it may turn out that some patients with HCC will either not benefit from the DAA therapies or may experience adverse events.


  1. Reig M, Mariño Z, Perelló C, et al. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy [published online April 13, 2016]. J Hepatol. doi:10.1016/j.jhep.2016.04.008.
  2. The ANRS collaborative study group on hepatocellular carcinoma. Lack of evidence of an effect of direct-acting antivirals on the recurrence of hepatocellular carcinoma: data from three ANRS cohorts [published online June 7, 2016]. J Hepatol. doi: 10.1016/j.jhep.2016.05.045.
  3. EMA reviews direct-acting antivirals for hepatitis C. European Medicines Agency website. Published April 15, 2016. Accessed September 11, 2016.


View more from the 2016 International Liver Cancer Association Annual Conference

There was a lower incidence of HCC recurrence among those who went on to receive DAA therapy than those who did not, said Nathalie Ganne-Carrié, MD, of Inserm, the French National Institute of Health and Medical Research.

Related Videos
View All
Related Content