Tenofovir Treatment Has Lower Risk of Hepatocellular Carcinoma than Entecavir Treatment in Patients with Chronic Hepatitis B: A Systematic Review and Meta-Analysis

Abstract

Tenofovir (TDF) and entecavir (ETV) are both equally recommended as first-line treatments for patients with chronic hepatitis B (CHB). They have comparable efficacy in virologic response, but their effect on the development of hepatocellular carcinoma (HCC) in CHB is controversial. Therefore, we aimed to compare TDF and ETV evaluating the risk of HCC development in CHB patients. Methods: A systematic literature search was conducted up to November 2019 in MEDLINE/PubMed, SCOPUS, and Web of Science databases without language and time restrictions. DerSimonian and Laird random-effects models were used to estimate combined hazard ratios (HRs) and 95% CIs. Results: Seven studies containing 35,785 participants were included in this systematic review and meta-analysis. The pooled HR (95% CI) of HCC in the patients who used TDF versus patients who used ETV was 0.75 (0.56-0.96). There was no significant heterogeneity detected among the included studies results (I 2 = 47.5%). There was no significant publication bias detected among the included studies (Begg's p = 0.88 and Egger's regression test p = 0.96). Conclusions: Evidence to date suggests that TDF treatment is associated with significantly fewer cases of HCC when compared to ETV.

No difference in hepatocellular carcinoma risk in chronic hepatitis B patients treated with tenofovir vs entecavir: evidence from an updated meta-analysis

“…The majority of previous meta-analyses found that TDF was associated with a lower risk of HCC than entecavir [ 20 – 28 ], which is inconsistent with our study. For example, a recent meta-analysis by Liu et al, including seven studies and 35785 CHB patients, found that patients on TDF treatment were at a lower risk of HCC than those on entecavir treatment (HR 0.75, 95% CI 0.56–0.96) [ 20 ].…”

“…The majority of previous meta-analyses found that TDF was associated with a lower risk of HCC than entecavir [ 20 – 28 ], which is inconsistent with our study. For example, a recent meta-analysis by Liu et al, including seven studies and 35785 CHB patients, found that patients on TDF treatment were at a lower risk of HCC than those on entecavir treatment (HR 0.75, 95% CI 0.56–0.96) [ 20 ]. The publication of several cohort studies motivates us to re-evaluate the potential differences in HCC incidence between TDF and entecavir groups, given that they consistently showed no difference in risk reduction of HCC between two groups [ 31 – 33 ].…”

“…However, whether they differ in the degree of improving such an outcome remains unclear [ 10 – 19 ]. A few meta-analyses on this topic had been published [ 20 – 30 ], but they presented inconclusive results. Specifically, most of them found that TDF was associated with a reduced risk of HCC compared with entecavir [ 20 – 28 ], while two contemporary meta-analyses failed to observe the putative superiority of TDF over entecavir in reducing the risk of HCC [ 29 , 30 ].…”

“…A few meta-analyses on this topic had been published [ 20 – 30 ], but they presented inconclusive results. Specifically, most of them found that TDF was associated with a reduced risk of HCC compared with entecavir [ 20 – 28 ], while two contemporary meta-analyses failed to observe the putative superiority of TDF over entecavir in reducing the risk of HCC [ 29 , 30 ]. More importantly, published meta-analyses could be severely affected by confounding bias, as they combined unadjusted risk estimates with adjusted risk estimates; also, they did not perform subgroup analyses to identify the potential effect modifiers for the comparative effectiveness of TDF vs entecavir in the prevention of HCC (e.g., cirrhosis).…”

Tenofovir Disoproxil Fumarate Is Superior to Entecavir in Reducing Hepatitis B Surface Antigen for Chronic Hepatitis B in China: 2-Year Comprehensive Comparative Result of a Matched Comparative Study

“…However, comparison of efficacy between ETV and TDF is still controversial. It is reported in a large proportion of studies including comparative studies and meta-analysis that TDF and ETV are comparable in treatment response, preventing occurrence of hepatocellular carcinoma and safety (20)(21)(22)(23)(24)(25)(26). A small number of studies suggest otherwise.…”