Mortality in patients with chronic hepatitis B treated with tenofovir or entecavir: A multinational study

Author:

Jang Tyng‐Yuan123ORCID,Liang Po‐Cheng12,Jun Dae Won4ORCID,Jung Jang Han5,Toyoda Hidenori6ORCID,Wang Chih‐Wen12ORCID,Yuen Man‐Fung78,Cheung Ka Shing7,Yasuda Satoshi6,Kim Sung Eun9,Yoon Eileen L4,An Jihyun10,Enomoto Masaru11,Kozuka Ritsuzo11,Chuma Makoto12,Nozaki Akito12ORCID,Ishikawa Toru13ORCID,Watanabe Tsunamasa14ORCID,Atsukawa Masanori15ORCID,Arai Taeang15,Hayama Korenobu15,Ishigami Masatoshi16,Cho Yong Kyun17,Ogawa Eiichi18,Kim Hyoung Su19,Shim Jae‐Jun20,Uojima Haruki21ORCID,Jeong Soung Won22,Ahn Sang Bong23,Takaguchi Koichi24,Senoh Tomonori24,Buti Maria25,Vargas‐Accarino i Elena25,Abe Hiroshi26,Takahashi Hirokazu2728ORCID,Inoue Kaori2728,Yeh Ming‐Lun1229ORCID,Dai Chia‐Yen1229ORCID,Huang Jee‐Fu1229ORCID,Huang Chung‐Feng122930ORCID,Chuang Wan‐Long1229,Nguyen Mindie H31,Yu Ming‐Lung12293233ORCID

Affiliation:

1. Division of Hepatobiliary, Department of Internal Medicine Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung Taiwan

2. Center of Hepatitis Research, College of Medicine and Center for Liquid Biopsy and Cohort Research Kaohsiung Medical University Kaohsiung Taiwan

3. Program of Environmental and Occupational Medicine and Graduate Institute of Clinical Medicine Kaohsiung Medical University Kaohsiung Taiwan

4. Department of Internal Medicine Hanyang University Hospital, Hanyang University College of Medicine Seoul South Korea

5. Division of Gastroenterology, Department of Internal Medicine Severance Hospital, Yonsei University College of Medicine Seoul South Korea

6. Department of Gastroenterology and Hepatology Ogaki Municipal Hospital Gifu Japan

7. Department of Medicine, School of Clinical Medicine Queen Mary Hospital, The University of Hong Kong Hong Kong

8. State Key Laboratory of Liver Research The University of Hong Kong Hong Kong

9. Department of Internal Medicine Hallym University Sacred Heart Hospital, Hallym University College of Medicine Anyang South Korea

10. Department of Internal Medicine Hanyang University Guri Hospital, Hanyang University College of Medicine Guri South Korea

11. Department of Hepatology, Graduate School of Medicine Osaka Metropolitan University Osaka Japan

12. Gastroenterological Center Yokohama City University Medical Center Yokohama Japan

13. Department of Gastroenterology Saiseikai Niigata Hospital Niigata Japan

14. Division of Gastroenterology and Hepatology St. Marianna University School of Medicine Kawasaki Japan

15. Division of Gastroenterology and Hepatology Nippon Medical School Tokyo Japan

16. Department of Gastroenterology and Hepatology Nagoya University Graduate School of Medicine Nagoya Japan

17. Department of Internal Medicine Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine Seoul South Korea

18. Department of General Internal Medicine Kyushu University Fukuoka Japan

19. Department of Internal Medicine Hallym University Kangdong Sacred Heart Hospital, Hallym University College of Medicine Seoul South Korea

20. Department of Internal Medicine Kyung Hee University Hospital, Kyung Hee University School of Medicine Seoul South Korea

21. Department of Gastroenterology and Internal Medicine Kitasato University School of Medicine Sagamihara Japan

22. Department of Internal Medicine Soonchunhyang University Hospital, Soonchunhyang University College of Medicine Seoul South Korea

23. Department of Internal Medicine, Nowon Eulji Medical Center Eulji University College of Medicine Seoul South Korea

24. Department of Hepatology Kagawa Prefectural Central Hospital Takamatsu Japan

25. Liver Unit Hospital Universitari Vall d'Hebron and CIBEREHD del Instituto Carlos III Barcelona Spain

26. Division of Gastroenterology and Hepatology Shinmatsudo Central General Hospital Chiba Japan

27. Liver Center Saga University Hospital Saga Japan

28. Division of Metabolism and Endocrinology, Faculty of Medicine Saga University Saga Japan

29. Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, and Center for Cancer Research and Liquid Biopsy Kaohsiung Medical University Kaohsiung Taiwan

30. PhD Program in Translational Medicine, College of Medicine Kaohsiung Medical University and Academia Sinica Kaohsiung Taiwan

31. Division of Gastroenterology and Hepatology, Department of Medicine Stanford University Medical Center Palo Alto California USA

32. School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease National Sun Yat‐sen University Kaohsiung Taiwan

33. Division of Hepato‐Gastroenterology, Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital Kaohsiung Taiwan

Abstract

AbstractBackground and AimThe benefits of entecavir (ETV) versus tenofovir disoproxil fumarate (TDF) in reducing the development of chronic hepatitis B (CHB)‐related hepatocellular carcinoma remain controversial. Whether mortality rates differ between patients with CHB treated with ETV and those treated with TDF is unclear.MethodsA total of 2542 patients with CHB treated with either ETV or TDF were recruited from a multinational cohort. A 1:1 propensity score matching was performed to balance the differences in baseline characteristics between the two patient groups. We aimed to compare the all‐cause, liver‐related, and non‐liver‐related mortality between patients receiving ETV and those receiving TDF.ResultsThe annual incidence of all‐cause mortality in the entire cohort was 1.0/100 person‐years (follow‐up, 15 757.5 person‐years). Patients who received TDF were younger and had a higher body mass index, platelet count, hepatitis B virus deoxyribonucleic acid levels, and proportion of hepatitis B e‐antigen seropositivity than those who received ETV. The factors associated with all‐cause mortality were fibrosis‐4 index > 6.5 (hazard ratio [HR]/confidence interval [CI]: 3.13/2.15–4.54, P < 0.001), age per year increase (HR/CI: 1.05/1.04–1.07, P < 0.001), alanine aminotransferase level per U/L increase (HR/CI: 0.997/0.996–0.999, P = 0.003), and γ‐glutamyl transferase level per U/L increase (HR/CI: 1.002/1.001–1.003, P < 0.001). No significant difference in all‐cause mortality was observed between the ETV and TDF groups (log–rank test, P = 0.69). After propensity score matching, no significant differences in all‐cause, liver‐related, or non‐liver‐related mortality were observed between the two groups.ConclusionsLong‐term outcomes of all‐cause mortality and liver‐related and non‐liver‐related mortality did not differ between patients treated with ETV and those receiving TDF.

Funder

Kaohsiung Medical University

Kaohsiung Medical University Chung-Ho Memorial Hospital

Publisher

Wiley

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