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

Abstract

Conflicting results have been reported regarding which of entecavir (ETV) or tenofovir disoproxil fumarate (TDF) is associated with better outcomes. Chronic hepatitis B patients who started ETV or TDF between 2010 and 2015 were analysed. The primary outcomes were hepatocellular carcinoma and death and transplantation. The impact of the treatment on the primary outcomes was analysed using Cox proportional hazards models in the entire and propensity score-matched cohorts. A total of 404 patients (180 and 224 in the ETV and TDF groups, respectively) were analysed. The median duration of follow-up was significantly longer in the ETV group (64.0 vs. 49.1 months; P < 0.001). Virological response (79.4% vs. 68.4%; P = 0.018) and sustained virological suppression (59.7% vs. 45.2%; P = 0.005) were significantly higher in the TDF group. TDF was associated with lower hepatocellular carcinoma [hazard ratio (HR) 0.31, 95% confidence interval (95% CI), 0.12-0.79; P = 0.014]; however, statistical significance was not reached after adjusting sustained virological suppression using propensity score matching (HR 0.36, 95% CI 0.12-1.14; P = 0.08). Death and transplantation was comparable. In conclusion, the impact of TDF on the lower hepatocellular carcinoma was blunted after adjusting sustained virological suppression. Further comparison in a larger number of patients who show sustained virological suppression over a longer period of time is needed.

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

“…Eight studies were conducted in Korea [ 10 , 11 , 13 , 15 – 17 , 31 , 33 ], one in the USA [ 19 ], two in China [ 14 , 32 ], one in the Europe [ 18 ], and one in the USA, China, Japan, and Korea [ 12 ]. The sample size of included studies ranged from 404 [ 33 ] to 29350 [ 14 ], with a total of 80202 patients. The follow-up duration varied from 3.0 years [ 15 ] to 7.1 years [ 18 ].…”

“…The follow-up duration varied from 3.0 years [ 15 ] to 7.1 years [ 18 ]. HBV DNA levels were somewhat lower in the TDF group than in the entecavir group in nine out of 13 included studies [ 10 – 15 , 19 , 31 , 33 ]. The quality of included studies was generally good, with an average score of 6.9 stars ( Supplementary Table 3 ).…”

“…No significant difference in the risk of HCC was found between TDF and entecavir groups (HR 0.86, 95% CI 0.72–1.04, I 2 =62.3%, P heterogeneity < 0.01) ( Figure 2 ). We then performed a propensity-score-matched meta-analysis, which included ten studies (11 cohorts) [ 10 – 17 , 31 , 33 ] with 18085 matched pairs ( Supplementary Table 4 ). Similar to the results of multivariable analysis, no significant difference in HCC incidence was found between TDF and entecavir groups (HR 0.83, 95% CI 0.66–1.03, I 2 =63.0%, P heterogeneity < 0.01) ( Figure 3 ).…”

“…Finally, for comparison with the results of multivariable-adjusted and propensity-score-matched meta-analyses, we performed a meta-analysis of unadjusted risk estimates. Based on 12 studies (13 cohorts) [ 10 – 19 , 31 , 33 ], HCC incidence was found to be significantly lower in the TDF group than in the entecavir group (HR 0.75, 95% CI 0.60–0.95, I 2 =80.9%, P heterogeneity < 0.01) ( Supplementary Figure 1 ).…”

“…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). In addition, several subsequent observational studies consistently found that there was no significant difference in HCC incidence between TDF and entecavir groups [ 31 – 33 ]; hence, it is essential to perform an updated meta-analysis to determine whether the results of previous meta-analyses persisted after including newly published studies.…”