Assessing the Risk of HCC for Hepatitis B Treatments

New research shows very little difference in the risk of hepatocellular carcinoma (HCC) for patients with chronic hepatitis B virus (HBV) treated with tenofovir compared to patients treated with entecavir.

A team, led by Darren Hun Hao Tan, Yong Loo Lin School of Medicine, National University of Singapore, reconstructed individual patient data to estimate the comparative risk of HCC between patients with chronic HBV treated with tenofovir or entecavir.

The Risk of HCC

Past research largely through conventional meta-analyses with aggregated study-level data, has been conflicting for comparing the effectiveness of tenofovir disoproxil fumarate with entecavir in reducing the risk of hepatocellular carcinoma in patients with chronic HBV.

In the study, the investigators searched databases for relevant studies from inception to October 6, 2021 and identified 3435 articles, 14 of which used propensity score matching to balance baseline characteristics.

The final analysis of the 14 studies included 24,269 total patients, 10,534 of which were treated with tenofovir and 13,735 of which were treated with entecavir. The mean age of the patient population was 49.86 years (95% CI, 48.35-51.36) and 65% of the patient population (95% CI, 58.60-71.00%) was male.

The team followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline and reconstructed individual patient data from Kaplan-Meier curves.

They also evaluated the risk of HCC using random-effects hazard ratios (HR) through a shared-frailty model and a Cox proportional hazards model stratified by study group.

Finally, they conducted a restricted mean survival time (RMST) analysis to account for varying estimated treatment effect across time.

The investigators sought main outcomes of the comparative risk of HCC in patients treated with tenofovir compared to patients treated with entecavir.

Tenofovir Vs Entecavir

Overall, tenofovir was linked to a decreased incidence rate of HCC compared to entecavir (stratified Cox HR, 0.85; 95% CI, 0.76-0.94 at 5 years; P = .002).

However, the investigators did not find a significant difference in their subanalysis of clinical cohort studies (stratified Cox HR, 0.92, 95% CI, 0.80-1.06 at 5 years; P = .24).

After examining administrative database studies, the team validated proportionality, while hazard ratios could not be obtained through Cox proportional hazards-based models.

They also found the mean time to developing HCC in the RMST analysis was 2.8 weeks longer (95% CI, 1.8-3.7; P <.001) in the tenofovir group than it was in the entecavir group at 5 years.

In other subgroups, there was either insignificant or minimal differences (<3 weeks) in the mean time to HCC at 5 years.

“In this meta-analysis, there was no clinically meaningful difference in the risk of HCC between patients who received entecavir and patients who received tenofovir,” the authors wrote. “There was no difference between tenofovir and entecavir among clinical cohort studies, whereas the mean time to HCC development was less than 3 weeks longer for patients who received tenofovir vs those who received entecavir at year 5 among administrative database studies. The choice between tenofovir or entecavir should be decided based on patient convenience and tolerability.”

The study, “Risk of Hepatocellular Carcinoma With Tenofovir vs Entecavir Treatment for Chronic Hepatitis B Virus,” was published online in JAMA Network Open.