Comparative Effectiveness of Entecavir Versus Tenofovir for Preventing Hepatocellular Carcinoma in Patients with Chronic Hepatitis B: A Systematic Review and Meta‐Analysis

Abstract

Background and Aims Chronic hepatitis B (CHB) can lead to hepatocellular carcinoma (HCC). While both tenofovir disoproxil (TDF) and entecavir (ETV) have been shown to reduce the risk of HCC, their comparative effectiveness is unclear. We estimated the comparative effectiveness of these two agents in reducing the risk of HCC in patients with CHB, through a systematic review and meta‐analysis. Approach and Results We searched multiple electronic databases from January 1, 1998, to October 31, 2019, for randomized controlled trials and observational comparative effectiveness studies in adults with CHB treated with ETV compared to TDF, reporting the incidence of HCC (minimum follow‐up 12 months). Primary outcome was incidence of HCC, calculated as incidence rate ratio (IRR) with 95% confidence interval (CI, unadjusted analysis) and hazard ratio (HR) with 95% CI (adjusted analysis, where reported). Of 1,971 records identified, 14 studies (263,947 person‐years) were included for quantitative analysis. On unadjusted meta‐analysis of 14 studies, the risk of HCC was not statistically different between ETV and TDF (IRR, 1.28; 95% CI, 0.99‐1.66). When using available adjusted data (multivariate or propensity‐matched data), the risk of HCC among patients treated with ETV was 27% higher when compared to TDF (seven studies; 95% CI, 1.01‐1.60, P = 0.04). Additional analysis of adjusted data when separately reported among patients with cirrhosis demonstrated an adjusted HR of 0.90 (95% CI, 0.66‐1.23), suggesting no difference between ETV‐treated and TDF‐treated groups. The overall confidence in estimates was very low (observational studies, high heterogeneity). Conclusions TDF may be associated with lower risk of HCC when compared to ETV.

Secondary prevention for hepatocellular carcinoma in patients with chronic hepatitis B: are all the nucleos(t)ide analogues the same?

“…and Dave et al . draw the similar conclusions that TDF may be associated with lower risk of HCC when compared to entecavir [ 56 , 57 ].…”

“…These studies concluded either both NAs are just as good, or TDF is better than entecavir in HCC prevention. Amidst all the controversies, two recent meta-analyses by Choi et al and Dave et al draw the similar conclusions that TDF may be associated with lower risk of HCC when compared to entecavir [56,57].…”

“…They showed by propensity score-matched analysis that there was no statistically significant difference between TDF and entecavir treatment on HCC risk, with an HR of 1.02. Thereafter, multiple observational studies and meta-analyses concerning the same clinical question on TDF vs. entecavir on HCC development in CHB patients have been published and continue to show that either TDF was associated with a lower risk of HCC than entecavir treatment, or TDF and entecavir treatment did not have a significant difference on the risk of HCC development (Table 1) [56,57]. One of the largest studies was conducted by the authors and colleagues based on a territory-wide retrospective cohort of 1309 and 28,041 patients treated by TDF and entecavir monotherapy in Hong Kong, respectively [58].…”

“…Summary of baseline characteristics and outcomes of studies comparing entecavir (ETV) and tenofovir disoproxil fumarate (TDF) treatment on risk of HCC development (Modified from Choi et al[57] and Dave et al[56] …”

Hepatocellular carcinoma and death and transplantation in chronic hepatitis B treated with entecavir or tenofovir disoproxil fumarate

“…www.nature.com/scientificreports/ Since Choi et al reported that TDF, in comparison with ETV, reduced HCC by analysing large insurance claim data and hospital cohorts 1 , subsequent studies have analysed the association between NAs and the incidence of HCC. However, they have failed to show consistent results [15][16][17][18][19][20][21][22] . Of note, a recent meta-analysis including more than 60,000 patients from 15 studies demonstrated that TDF significantly reduced the risk of HCC by 20% 23 .…”