From the AGA Journals

AGA Clinical Practice Update: Direct-acting antivirals and hepatocellular carcinoma



Achieving sustained virologic response to direct-acting antiviral therapy for chronic hepatitis C virus infection cuts lifetime hepatocellular carcinoma risk by approximately 70%, even when patients have baseline cirrhosis, experts wrote in Gastroenterology.

Dr. Amit G. Singal

When used after curative-intent treatment for hepatocellular carcinoma, direct-acting antiviral (DAA) therapy also does not appear to make recurrent cancer more probable or more aggressive, wrote Amit G. Singal, MD, and associates in an American Gastroenterological Association clinical practice update. Studies that compared DAA therapy with either interferon-based therapy or no treatment have found “similar if not lower recurrence than the comparator groups,” they wrote. Rather, hepatocellular carcinoma is in itself highly recurrent: “While surgical resection and local ablative therapies are considered curative, [probability of] recurrence approaches 25%-35% within the first year, and 50%-60% within 2 years.”

Direct-acting antiviral therapy for chronic hepatitis C infection improves several aspects of liver health, but experts have debated whether and how these benefits affect the risk and behavior of hepatocellular carcinoma. To explore the issue, Dr. Singal, medical director of the liver tumor program and clinical chief of hepatology at UT Southwestern Medical Center in Dallas and associates reviewed published clinical trials, observational studies, and systematic reviews. Among 11 studies of more than 3,000 patients in five countries, sustained virologic response (SVR) to DAA therapy was associated with about a 70% reduction in the risk of liver cancer, even after adjustment for clinical and demographic variables. “The relative reduction is similar in patients with and without cirrhosis,” the experts wrote.

Since patients with fibrosis (F3) or cirrhosis are at highest risk for hepatocellular carcinoma, they should undergo baseline imaging and remain under indefinite post-SVR surveillance as long as they are eligible for potentially curative treatment, the practice update states. The experts recommended twice-yearly ultrasound, with or without serum alpha-fetoprotein, noting that current evidence supports neither shorter surveillance intervals nor alternative imaging modalities.

“The presence of active hepatocellular carcinoma is associated with a small but statistically significant decrease in SVR with DAA therapy,” the experts confirmed, based on the results of three studies. They recommended that, when possible, patients with hepatocellular carcinoma first receive curative-intent treatment, such as with liver resection or ablation. Direct-acting antiviral therapy can begin 4-6 months later, once there has been time to confirm response to hepatocellular carcinoma treatment.

For patients who are listed for liver transplantation, timing of DAA therapy “should be determined on a case-by-case basis with consideration of median wait times for the region, availability of HCV-positive organs, and degree of liver dysfunction,” they added. “For example, DAA therapy may be beneficial pretransplant for patients in regions with long wait times or limited hepatitis C virus–positive donor organ availability, whereas therapy may be delayed until posttransplant in regions with shorter wait times or a high proportion of hepatitis C virus–positive donor organs that would otherwise go unused.”

For patients with active intermediate or advanced liver cancer, it remains unclear whether DAA therapy is usually worth the costs and risks, they noted. This is because the likelihood of complete response is lower and the competing risk of death is higher than in patients with earlier-stage hepatocellular carcinoma. Pending further data, they recommend basing the decision on patients’ preferences, tumor burden, degree of liver dysfunction, and life expectancy. At their institutions, the researchers do not treat patients with DAA therapy unless their life expectancy exceeds 2 years.

The experts disclosed research funding from the National Cancer Institute, U.S. Veterans Administration, and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Singal reported personal fees or research funding from AbbVie, Bayer, Bristol-Myers Squibb, Eisai, Exact Sciences, Exelixis, Gilead, Glycotest, Roche, and Wako Diagnostics. His coauthors disclosed ties to AbbVie, Allergan, Bristol-Myers Squibb, Conatus, Genfit, Gilead, Intercept, and Merck.

SOURCE: Singal AG et al. Gastroenterology. 2019 Mar 13. doi: 10.1053/j.gastro.2019.02.046.

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