GOALS This meta-analysis evaluated the comparative effectiveness of tenofovir disoproxil fumarate (TDF) versus entecavir (ETV) in reducing the risk of hepatocellular carcinoma (HCC).

BACKGROUND It is unclear whether TDF or ETV is more effective in reducing the risk of HCC in chronic hepatitis B (CHB) patients with or without underlying cirrhosis.

METHODS We searched the MEDLINE database through April 13, 2020, for studies involving CHB treated with TDF and/or ETV. Primary and secondary outcomes were the incidence of HCC and overall survival, respectively, calculated as risk ratios (RRs). Adjusted results were further evaluated by pooling propensity score matched cohorts.

RESULTS Of the 229 records identified, 17 studies were included in the quantitative analysis. TDF treatment was associated with a significantly lower risk of HCC development [RR, 0.63; 95% confidence interval (CI), 0.43-0.93; P=0.024] and mortality (RR, 0.69; 95% CI, 0.57-0.84; P=0.003) than ETV treatment. Moreover, TDF significantly lowered HCC risk in patients with cirrhosis (RR, 0.69; 95% CI, 0.56-0.84) and antiviral treatment-naive patients (RR, 0.59; 95% CI, 0.35-0.98) compared with ETV. Among treatment-naive patients, TDF significantly prolonged survival compared with ETV (RR, 0.69; 95% CI, 0.52-0.91).

CONCLUSIONS TDF likely confers a lower risk of HCC development and longer survival in patients with CHB, especially among treatment-naive patients and those with underlying cirrhosis, than ETV.