Hep B Liver Cancer Risk Comparable With Tenofovir, Entecavir

Chronic hepatitis B patients face similar risk liver cancer risks whether treated with tenofovir or entecavir, according to a systematic review and meta-analysis.

"The key purpose of our research program is to advocate for antiviral therapy for patients with active chronic hepatitis B to prevent liver cancer and to save lives," Dr. Mindie Nguyen of Stanford University in Palo Alto and Dr. Yao-Chun (Holden) Hsu of EDA Hospital in Kaohsiung, Taiwan, told Reuters Health.

"To that end, we are glad to have confirmed that the two most commonly used and widely available antiviral agents are both effective and equally so in preventing liver cancer," they said by email. "This is important so patients and physicians can select whichever agent most affordable and most appropriate for patient safety and tolerability."

As reported in The Lancet Gastroenterology and Hepatology, the team searched the literature from 2006-2020, and conference abstracts in 2018 and 2019, and analyzed 31 relevant studies involving more than 119,000 chronic hepatitis B patients.

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The five-year cumulative incidence of hepatocellular carcinoma in unmatched populations was 5.97% for entecavir (28 studies) and 3.06% (13 studies) for tenofovir.

For eight studies matched by propensity score, the five-year cumulative incidence was 3.44% for entecavir and 3.39% for tenofovir.

An analysis of 14 comparative studies with covariate adjustment found that tenofovir and entecavir had a similar hepatocellular cancer risk (adjusted hazard ratio, 0.88), although heterogeneity was significant.

In a subgroup analysis for hospital-based cohorts, no difference in hepatocellular incidence was seen between the antivirals (adjusted HR, 1.03). However, in administrative database research, tenofovir was associated with a lower risk compared with entecavir (adjusted HR, 0.67).

"The field has spent much effort to investigate this topic since the initial observation favoring tenofovir from South Korea a few years ago," Drs. Nguyen and Yao-Chun said. "We don't believe more work in this area is needed. Instead, we should focus on finding a cure for chronic hepatitis B while escalating our efforts to find and diagnose the 250-290 million people already infected around the world, many of whom may benefit from treatment with one of these two antiviral agents or equivalent."

Dr. Gail Matthews of Kirby Institute, UNSW Sydney, coauthor of a related editorial, commented in an email to Reuters Health. Like the authors, she said, "This meta-analysis provides important data to reassure clinicians that there is no evidence for differential risk between entecavir and tenofovir for liver cancer development. In fact, both of these agents are important drugs in their ability to reduce liver cancer risk in people living with chronic hepatitis B."

"The ideal study still needed would be a randomized head-to-head comparison of the two drugs," she added. "But given this is very unlikely to ever be feasible, unless strong evidence from well conducted alternative studies to the contrary becomes available, this most recent study should provide strong reassurance to clinicians."

—Marilynn Larkin

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