Lower liver-cancer risk seen with tenofovir treatment of chronic hepatitis B

Last Updated: 2018-10-04

By Will Boggs MD

NEW YORK (Reuters Health) - The risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) treated with tenofovir is lower than in those treated with entecavir, according to a nationwide study from South Korea.

"Patients with CHB have about 1% risk of developing HCC," Dr. Young-Suk Lim from the University of Ulsan College of Medicine, in Seoul, told Reuters Health by email. "Once diagnosed with HCC, the overall prognosis of the patients is very poor, with 5-year survival rate of less than 30%. Therefore, prevention of HCC is of utmost importance in the management of CHB patients."

Entecavir and tenofovir disoproxil fumarate (TDF), first-line antiviral agents for CHB infection, have similar efficacy for intermediate-term virologic, biochemical, serologic and histologic outcomes. Their relative efficacy in reducing HCC risk remains uncertain.

Dr. Lim's team used data from the National Health Insurance Service of the Republic of Korea to compare the effectiveness of entecavir and tenofovir on the risk of HCC in patients with CHB.

During follow-up, the incidence of HCC was significantly lower in the tenofovir group (0.64 per 100 person-years) than in the entecavir group (1.06 per 100 person-years), the researchers report in JAMA Oncology, online September 27.

In a propensity-score-matched analysis, the risk of HCC diverged between the two groups after two years' follow-up and became 38% lower in the tenofovir group over time.

The annual rate of all-cause mortality or liver transplant was 23% lower in the tenofovir group by multivariable analysis and 21% lower in the tenofovir group by propensity score-matched analysis, both significant differences.

In a validation cohort of 2,701 patients with CHB infection who commenced treatment with entecavir or tenofovir, virologic response rates were significantly lower in the entecavir group (78.7%) than in the tenofovir group (85.2%), and tenofovir treatment was independently associated with a 34% lower risk of HCC.

The risk of death or transplant did not differ between the two treatment groups in the validation cohort.

"Oral antiviral agents to treat CHB patients are not the same in terms of cancer prevention," Dr. Lim concluded. "Our findings suggest that we could reduce HCC incidence as much as 35% by selecting TDF rather than entecavir (ETV), and it may have considerable clinical implications for preventing the occurrence of HCC in patients with CHB."

This "work is the first to our knowledge to suggest that TDF offers advantages over ETV in terms of HCC prevention, but given the inherent limitations of observational data, this study should not lead to a widespread paradigm shift in selecting TDF over ETV," write Dr. Jennifer A. Flemming from Queen's University, in Kingston, Canada, and Dr. Norah H. Terrault from the University of California, San Francisco, in a linked editorial. "Rather, it should spur more investigators to address the issue of whether one of these HBV drugs is not like the other."

Dr. Hashem B. El-Serag from Baylor College of Medicine, in Houston, Texas, who studies the epidemiology of hepatocellular carcinoma, told Reuters Health by email, "Successful treatment of chronic HBV results in a reduction in HCC risk. The adequacy of HBV suppression was not examined in the national-database portion of the study; this is essential in order to understand/believe the findings."

"Given that this is only one observational study from Korea, additional evidence is required," he said. "As noted by the authors, previous observational studies did not find differences in HCC risk between those treated with tenofovir or entecavir."

"I believe it is still premature to choose tenofovir preferentially over entecavir for the possible additional HCC reductive effect," Dr. El-Serag said.

SOURCE: https://bit.ly/2IG5Na8 and https://bit.ly/2O7TsRN

JAMA Oncol 2018.