Hepatocellular carcinoma risk in patients with chronic hepatitis B receiving tenofovir- vs. entecavir-based regimens: Individual patient data meta-analysis
Year: 2022
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: BACKGROUND & AIMS: The comparative risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) receiving tenofovir disoproxil fumarate (TDF) vs. entecavir (ETV) remains controversial. In this individual patient data (IPD) meta-analysis, we aimed to compare HCC risk between the two drugs and identify subgroups who may benefit more from one treatment than the other. METHODS: Published meta-analyses, electronic databases and congress proceedings were searched to identify eligible studies through January 2021. We compared HCC risk between the two drugs using a multivariable Cox proportional hazards model with anonymised IPD from treatment-naïve patients with CHB receiving TDF or ETV for ≥1 year. Treatment effect consistency was explored in propensity score matching (PSM), weighting (PSW) and subgroup analyses for age, sex, hepatitis B e-antigen (HBeAg) positivity, cirrhosis and diabetes status. RESULTS: We included 11 studies from Korea, Taiwan and Hong Kong involving 42,939 patients receiving TDF (n = 6,979) or ETV (n = 35,960) monotherapy. Patients receiving TDF had significantly lower HCC risk (adjusted hazard ratio [HR] 0.77; 95% CI 0.61-0.98; p = 0.03). Lower HCC risk with TDF was consistently observed in PSM (HR 0.73; 95% CI 0.59-0.88; p <0.01) and PSW (HR 0.83; 95% CI 0.67-1.03; p = 0.10) analyses and in all subgroups, with statistical significance in the ≥50 years of age (HR 0.76; 95% CI 0.58-1.00; p <0.05), male (HR 0.74; 95% CI 0.58-0.96; p = 0.02), HBeAg-positive (HR 0.69; 95% CI 0.49-0.97; p = 0.03) and non-diabetic (HR 0.79; 95% CI 0.63-1.00; p <0.05) subgroups. CONCLUSION: TDF was associated with significantly lower HCC risk than ETV in patients with CHB, particularly those with HBeAg positivity. Longer follow-up may be needed to better define incidence differences between the treatments in various subgroups. IMPACT AND IMPLICATIONS: Previous aggregate data meta-analyses have reported inconsistent conclusions on the relative effectiveness of tenofovir disoproxil fumarate and entecavir in reducing hepatocellular carcinoma risk in patients with chronic hepatitis B (CHB). This individual patient data meta-analysis on 11 studies involving 42,939 patients from Korea, Taiwan and Hong Kong suggested that tenofovir disoproxil fumarate-treated patients have a significantly lower hepatocellular carcinoma risk than entecavir-treated patients, which was observed in all subgroups of clinical interest and by different analytical methodologies. These findings should be taken into account by healthcare providers when determining the optimal course of treatment for patients with CHB and may be considered in ensuring that treatment guidelines for CHB remain pertinent.
Source: Journal of Hepatology
Authors: Won-Mook Choi, Terry Cheuk-Fung Yip, Grace Lai-Hung Wong, W. Ray Kim, Leland J. Yee, Craig Brooks-Rooney, Tristan Curteis, Harriet Cant, Chien-Hung Chen, Chi-Yi Chen, Yi-Hsiang Huang, Young-Joo Jin, Dae Won Jun, Jin-Wook Kim, Neung Hwa Park, Cheng-Yuan Peng, Hyun Phil Shin, Jung Woo Shin, Yao-Hsu Yang, Young-Suk Lim
Institutions: Asan Medical Center, University of Ulsan, Chinese University of Hong Kong, Stanford Medicine, Stanford University, Gilead Sciences (United States), Costello Medical Consulting (United Kingdom), Chang Gung University, Kaohsiung Chang Gung Memorial Hospital, Chia-Yi Christian Hospital, National Yang Ming Chiao Tung University, Taipei Veterans General Hospital, Inha University, Inha University Hospital, Hanyang University Seoul Hospital, Hanyang University Medical Center, Seoul National University, Seoul National University Bundang Hospital, Ulsan University Hospital, China Medical University, China Medical University Hospital, Kyung Hee University, Kyung Hee University Hospital at Gangdong, Chang Gung Memorial Hospital, Chiayi Chang Gung Memorial Hospital
Language: English
Topic: Hepatitis B Virus Studies
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Funders: Gilead Sciences, Seoul National University Bundang Hospital, Hanyang University, Seoul National University, University of Ulsan, Kyung Hee University, Inha University, Chang Gung University, Shanghai Educational Development Foundation, China Medical University Hospital, Chang Gung Medical Foundation, Chinese University of Hong Kong, China Medical University, Taipei Veterans General Hospital, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Inha University Hospital, School of Medicine, Stanford University, College of Medicine, Seoul National University, Kaohsiung Chang Gung Memorial Hospital, Chiayi Chang Gung Memorial Hospital, Ulsan University Hospital
OpenAlex ID: W4312157397