Min Li1, Tingting Lv2, Shanshan Wu1, Wei Wei1, Xiaohai Wu3, Xiaojuan Ou2, Hong Ma2, Shein-Chung Chow4, Yuanyuan Kong5, Hong You6, Jidong Jia7. 1. Clinical Epidemiology and EBM Unit, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China. 2. Liver Research Center, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China. 3. Library of Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China. 4. Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, 27708, USA. 5. Clinical Epidemiology and EBM Unit, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China. kongyy@ccmu.edu.cn. 6. Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China. youhongliver@ccmu.edu.cn. 7. Liver Research Center, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, China. jia_jd@ccmu.edu.cn.
Abstract
BACKGROUND: Controversy exists on whether tenofovir disoproxil fumarate (TDF) is superior to entecavir (ETV) in lowering the risk of hepatocellular carcinoma (HCC) development. This meta-analysis was performed to clarify this issue with critical clinical and methodological considerations. METHODS: PubMed, EMBASE, and Cochrane Library were searched from inception to Oct 28, 2019. Randomized control trials and observational studies reporting the impact of TDF and ETV on the risk of HCC in patients with chronic hepatitis B (CHB) were eligible. Risk ratios (RRs) calculated with cumulative incidence rate and/or annual incidence rate, or hazard ratio (HR) were pooled using random-effect models. Subgroup analyses were performed to assess the potential impact of between-study level and within-study level factors. RESULTS: A total of 32 studies with 78,136 CHB patients were included. Overall cumulative incidence rate of HCC was lower in TDF group than ETV group (3.07% vs. 5.25%; RR 0.55; 95% CI 0.42-0.72). However, this difference was not statistically significant in pooled results of hazard ratio (HR 0.87; 95% CI 0.73-1.04) and RR calculated with annual incidence rate (RR 0.88; 95% CI 0.67-1.16). Potential confounding factors at between-study level included prior nucleos(t)ide usage, disease stage at baseline and region of study. More importantly, at within-study level, disparity in follow-up duration between TDF and ETV groups may impact the result, usually favoring a treatment with shorter follow-up duration. CONCLUSIONS: Compared with ETV, TDF treatment tended to have a lower overall cumulative incidence rate of HCC. However, disparity in follow-up duration may be a key factor to influence the result.
BACKGROUND: Controversy exists on whether tenofovir disoproxil fumarate (TDF) is superior to entecavir (ETV) in lowering the risk of hepatocellular carcinoma (HCC) development. This meta-analysis was performed to clarify this issue with critical clinical and methodological considerations. METHODS: PubMed, EMBASE, and Cochrane Library were searched from inception to Oct 28, 2019. Randomized control trials and observational studies reporting the impact of TDF and ETV on the risk of HCC in patients with chronic hepatitis B (CHB) were eligible. Risk ratios (RRs) calculated with cumulative incidence rate and/or annual incidence rate, or hazard ratio (HR) were pooled using random-effect models. Subgroup analyses were performed to assess the potential impact of between-study level and within-study level factors. RESULTS: A total of 32 studies with 78,136 CHBpatients were included. Overall cumulative incidence rate of HCC was lower in TDF group than ETV group (3.07% vs. 5.25%; RR 0.55; 95% CI 0.42-0.72). However, this difference was not statistically significant in pooled results of hazard ratio (HR 0.87; 95% CI 0.73-1.04) and RR calculated with annual incidence rate (RR 0.88; 95% CI 0.67-1.16). Potential confounding factors at between-study level included prior nucleos(t)ide usage, disease stage at baseline and region of study. More importantly, at within-study level, disparity in follow-up duration between TDF and ETV groups may impact the result, usually favoring a treatment with shorter follow-up duration. CONCLUSIONS: Compared with ETV, TDF treatment tended to have a lower overall cumulative incidence rate of HCC. However, disparity in follow-up duration may be a key factor to influence the result.
Authors: Sahil Mittal; Jennifer R Kramer; Ronald Omino; Maneerat Chayanupatkul; Peter A Richardson; Hashem B El-Serag; Fasiha Kanwal Journal: Clin Gastroenterol Hepatol Date: 2017-09-01 Impact factor: 11.382
Authors: Seung Up Kim; Yeon Seok Seo; Han Ah Lee; Mi Na Kim; Yu Rim Lee; Hye Won Lee; Jun Yong Park; Do Young Kim; Sang Hoon Ahn; Kwang-Hyub Han; Seong Gyu Hwang; Kyu Sung Rim; Soon Ho Um; Won Young Tak; Young Oh Kweon; Beom Kyung Kim; Soo Young Park Journal: J Hepatol Date: 2019-04-06 Impact factor: 25.083
Authors: Darren Jun Hao Tan; Cheng Han Ng; Phoebe Wen Lin Tay; Nicholas Syn; Mark D Muthiah; Wen Hui Lim; Ansel Shao Pin Tang; Kai En Lim; Grace En Hui Lim; Nobuharu Tamaki; Beom Kyung Kim; Margaret Li Peng Teng; James Fung; Rohit Loomba; Mindie H Nguyen; Daniel Q Huang Journal: JAMA Netw Open Date: 2022-06-01