Liver cancer patients should receive direct-acting antivirals with highest response rates

The use of direct-acting antiviral agents (DAAs) in patients with hepatocellular carcinoma (HCC) requires specific considerations when planning the timing and course of treatment, as well as determining subsequent follow-up, according to a new study.

The use of DAAs for patients with hepatitis C virus (HCV) has transformed treatment, with cure rates of more than 90% in the vast majority of patients previously considered difficult to treat, including those with prior treatment experience, genotype 3, coinfection with HIV, patients with kidney or liver transplants, and advanced cirrhosis. However, data regarding potential treatment benefits versus risks of DAAs in HCV patients with HCC, or a prior history of HCC, are only now beginning to emerge and may impact future treatment recommendations, said senior author Behnam Saberi, MD, of the Icahn School of Medicine at Mount Sinai in New York.

“Potentially lower SVR rates seen in patients with HCC may require selection of DAAs that have been associated with the highest SVR rates in clinical trials, as well as the potential addition of ribavirin to further boost SVR rates,” said Saberi. Also, the presence of HCC may affect the timing of DAA treatment, especially in regards to liver transplantation.

The researchers published their results in March 2018 Current Opinion in Gastroenterology.

The current data on the use of DAAs in HCC patients are largely drawn from retrospective cohort studies. The majority of the studies show a lower sustained virologic response (SVR) in HCC patients, which may be related in part to the extent of the HCC, although it remains unclear whether the volume of HCC tumors or the number of prior HCC treatments plays a role, he said.

Clinicians must consider host/viral factors that will affect SVR rates. These factors include: type of DAA, duration of therapy, with or without ribavirin, proportion of genotype 3, treatment-experienced (prior protease inhibitors or NS5A inhibitor exposures), degree of liver decompensation, and clinically relevant resistant-associated variants. In addition, attention should be given to number, size, and stage of HCC in determining response of patients with HCC to DAA therapy, said Saberi.

A number of studies have evaluated potential HCC recurrence. Earlier studies suggested an increase in HCC recurrence rates, but subsequent larger, prospective studies suggest that treatment with DAAs may actually decrease recurrence risk, he said.

In order to truly validate lower SVR rates in HCC patients, prospective, double-blind clinical trials in HCV/HCC patients on various DAA regimens as well as potentially longer duration of therapy are needed.

“Well-designed future studies are required to evaluate the optimal timing of HCV treatment in patients with HCC on the liver transplant list. Patients with advanced stage HCC and patients with HCC and significant liver decompensation who are not liver transplant candidates may not benefit from DAA therapy given short-term survival. DAA therapy in these patients, however, may improve or stabilize the liver function to some extent and slightly improve quality of life,” said Saberi.