Yao-Chun Hsu1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26, Grace Lai-Hung Wong5, Chien-Hung Chen6, Cheng-Yuan Peng7, Ming-Lun Yeh8, Ka-Shing Cheung9, Hidenori Toyoda10, Chung-Feng Huang8, Huy Trinh11, Qing Xie12, Masaru Enomoto13, Li Liu14, Satoshi Yasuda10, Yasuhito Tanaka15, Ritsuzo Kozuka13, Pei-Chien Tsai8, Yen-Tsung Huang16, Christopher Wong17, Rui Huang18, Tyng-Yuan Jang8, Joseph Hoang19, Hwai-I Yang20, Jiayi Li21, Dong-Hyun Lee22, Hirokazu Takahashi23, Jian Q Zhang24, Eiichi Ogawa25, Changqing Zhao26, Chenghai Liu26, Norihiro Furusyo25, Yuichiro Eguchi23, Clifford Wong17, Chao Wu18, Takashi Kumada10, Man-Fung Yuen9, Ming-Lung Yu8, Mindie H Nguyen19. 1. Division of Gastroenterology and Hepatology, E-Da Hospital, Kaohsiung, Taiwan. 2. Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan. 3. School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan. 4. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan. 5. Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong SAR, China. 6. Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 7. Department of Gastroenterology, China Medical University Hospital, Taichung, Taiwan. 8. Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 9. Department of Medicine, the University of Hong Kong, Hong Kong SAR, China. 10. Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan. 11. San Jose Gastroenterology, San Jose, California, USA. 12. Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China. 13. Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan. 14. Department of Infection Disease, the Third Hospital of Kumming City, Kumming, People's Republic of China. 15. Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. 16. Institute of Statistical Science, Academia Sinica, Taipei, Taiwan. 17. Wong Clinics, San Francisco, California, USA. 18. Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, People's Republic of China. 19. Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, the United States of America. 20. Genomics Research Center, Academia Sinica, Taipei, Taiwan. 21. Palo Alto Medical Foundation, Mountain View Division, Mountain View, California, USA. 22. Department of Gastroenterology, Good Gang-An Hospital, Busan, Sourth Korea. 23. Department of Internal Medicine, Saga University Hospital, Saga, Japan. 24. Chinese Hospital, San Francisco, California, USA. 25. Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan. 26. Department of Cirrhosis, Institute of Liver Disease, Shuguang Hospital affiliated to Shanghai University of T.C.M., Shanghai, People's Republic of China.
Abstract
INTRODUCTION: It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) differ in their effectiveness for preventing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). METHODS: This retrospective cohort study analyzed an international consortium that encompassed 19 centers from 6 countries or regions composed of previously untreated CHB patients then treated with either ETV or TDF monotherapy. Those who developed HCC before antiviral treatment or within 1 year of therapy were excluded. The association between antiviral regimen and HCC risk was evaluated using competing-risk survival regression. We also applied propensity score matching (PSM) to 1:1 balance the 2 treatment cohorts. A total of 5,537 patients were eligible (n = 4,837 received ETV and n = 700 received TDF) and observed for HCC occurrence until December 23, 2018. Before PSM, the TDF cohort was significantly younger and had generally less advanced diseases. RESULTS: In the unadjusted analysis, TDF was associated with a lower risk of HCC (subdistribution hazard ratio [SHR], 0.45; 95% confidence interval [CI], 0.26-0.79; P = 0.005). The multivariable analysis, however, found that the association between TDF and HCC no longer existed (SHR, 0.81; 95% CI, 0.42-1.56; P = 0.52) after adjustment for age, sex, country, albumin, platelet, α-fetoprotein, cirrhosis, and diabetes mellitus. Furthermore, the PSM analysis (n = 1,040) found no between-cohort differences in HCC incidences (P = 0.51) and no association between regimens (TDF or ETV) and HCC risk in the multivariable-adjusted analysis (adjusted SHR, 0.89; 95% CI, 0.41-1.92; P = 0.77). DISCUSSION: TDF and ETV did not significantly differ in the prevention of HCC in patients with CHB.
INTRODUCTION: It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) differ in their effectiveness for preventing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). METHODS: This retrospective cohort study analyzed an international consortium that encompassed 19 centers from 6 countries or regions composed of previously untreated CHB patients then treated with either ETV or TDF monotherapy. Those who developed HCC before antiviral treatment or within 1 year of therapy were excluded. The association between antiviral regimen and HCC risk was evaluated using competing-risk survival regression. We also applied propensity score matching (PSM) to 1:1 balance the 2 treatment cohorts. A total of 5,537 patients were eligible (n = 4,837 received ETV and n = 700 received TDF) and observed for HCC occurrence until December 23, 2018. Before PSM, the TDF cohort was significantly younger and had generally less advanced diseases. RESULTS: In the unadjusted analysis, TDF was associated with a lower risk of HCC (subdistribution hazard ratio [SHR], 0.45; 95% confidence interval [CI], 0.26-0.79; P = 0.005). The multivariable analysis, however, found that the association between TDF and HCC no longer existed (SHR, 0.81; 95% CI, 0.42-1.56; P = 0.52) after adjustment for age, sex, country, albumin, platelet, α-fetoprotein, cirrhosis, and diabetes mellitus. Furthermore, the PSM analysis (n = 1,040) found no between-cohort differences in HCC incidences (P = 0.51) and no association between regimens (TDF or ETV) and HCC risk in the multivariable-adjusted analysis (adjusted SHR, 0.89; 95% CI, 0.41-1.92; P = 0.77). DISCUSSION: TDF and ETV did not significantly differ in the prevention of HCC in patients with CHB.
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