The American Gastroenterological Association has collected evidence describing interactions between oral direct-acting antiviral (DAA) therapy for hepatitis C and hepatocellular cancer with regard to incidence, recurrence, and efficacy. This has resulted in an updated summary of best practice advice for surveillance of hepatocellular cancer and DAA therapy timing, according to a clinical practice update published in Gastroenterology. This update provided best practice recommendations based on published evidence.
First, DAA treatments are associated with hepatocellular cancer incident risk reduction, and the relative reduction is similar for patients with and without cirrhosis. For patients with cirrhosis achieving sustained virologic response, hepatocellular cancer incidence and hepatocellular cancer survival was similar between DAA-treated patients and interferon-treated patients (21.2 vs 22.8 per 1,000 person-years; P =.78 and log-rank P =.17, respectively). Overall, achieving sustained virologic response resulted in a ~70% hepatocellular cancer risk reduction, which was evident within 3 to 6 months and increased over time.
Further, the most important hepatocellular cancer precursor lesion in patients with hepatitis C is cirrhosis or advanced fibrosis, and absolute hepatocellular cancer risk remains high with DAA treatment at the time of sustained virologic response (1.8% to 2.5% overall annual risk), exceeding the cut-off for cost-effective hepatocellular cancer surveillance (0.8 to 1.5% per year). Therefore, all patients with cirrhosis or advanced liver fibrosis should receive surveillance imaging prior to DAA initiation. In addition, patients with an advanced case of cirrhosis at the time of treatment should receive hepatocellular cancer surveillance, performed using ultrasound every 6 months, after achieving sustained virologic response. The researchers stated that while future studies may show a hepatocellular cancer risk reduction over time, current evidence supports continual surveillance, indefinitely.
In addition, DAA therapy for patients with active hepatocellular cancer has been associated with a statistically significant, though small, decrease in sustained virologic response, and patients eligible for potentially curative ablation or liver resection should defer DAA therapy. Median wait times, hepatitis C-positive organ availability, and the level of liver dysfunction should be considered when determining DAA therapy timing for patients with hepatocellular cancer who are on a list for liver transplant.
Lastly, conflicting studies fail to show conclusive data that DAA therapy is associated with differential time-to-recurrence, decreased or increased risk, or recurrent hepatocellular cancer aggressiveness in patients who achieve complete response to hepatocellular cancer therapy. DAA therapy should not be withheld from these patients, but DAA therapy can be deferred for 4 to 6 months to confirm therapy response, as those with complete response have continued recurrence risk of hepatocellular cancer, and require indefinite surveillance every 3 to 6 months with dynamic contrast enhanced computerized tomography or magnetic resonance imaging.
Authors report conflicts of interest due to research funding and consulting for Abbvie, Allergan, Bayer, Bristol-Myers Squibb, Conatus, Exact Sciences, Eisai, Exelixis, Gilead, Genfit, Glycotest, Merck, Roche, and Wako Diagnostics.
Singal AG, Lim JK, Kanwal F. AGA clinical practice update on interaction between oral direct-acting antivirals (DAAs) for chronic hepatitis C infection and hepatocellular carcinoma: expert review [published online March 13, 2019]. Gastroenterology. doi: 10.1053/j.gastro.2019.02.046