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

Tyng-Yuan Jang^{1

2

3}, Po-Cheng Liang^{1

2}, Dae Won Jun⁴, Jang Han Jung⁵, Hidenori Toyoda⁶, Chih-Wen Wang^{1

2}, Man-Fung Yuen^{7

8}, Ka Shing Cheung⁷, Satoshi Yasuda⁶, Sung Eun Kim⁹, Eileen L Yoon⁴, Jihyun An¹⁰, Masaru Enomoto¹¹, Ritsuzo Kozuka¹¹, Makoto Chuma¹², Akito Nozaki¹², Toru Ishikawa¹³, Tsunamasa Watanabe¹⁴, Masanori Atsukawa¹⁵, Taeang Arai¹⁵, Korenobu Hayama¹⁵, Masatoshi Ishigami¹⁶, Yong Kyun Cho¹⁷, Eiichi Ogawa¹⁸, Hyoung Su Kim¹⁹, Jae-Jun Shim²⁰, Haruki Uojima²¹, Soung Won Jeong²², Sang Bong Ahn²³, Koichi Takaguchi²⁴, Tomonori Senoh²⁴, Maria Buti²⁵, Elena Vargas-Accarino I²⁵, Hiroshi Abe²⁶, Hirokazu Takahashi^{27

28}, Kaori Inoue^{27

28}, Ming-Lun Yeh^{1

2

29}, Chia-Yen Dai^{1

2

29}, Jee-Fu Huang^{1

2

29}, Chung-Feng Huang^{1

2

29

30}, Wan-Long Chuang^{1

2

29}, Mindie H Nguyen³¹, Ming-Lung Yu^{1

2

29

32

33}

Affiliations

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.

PMID: 38480009
DOI: 10.1111/jgh.16537

Multicenter Study

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

Tyng-Yuan Jang et al. J Gastroenterol Hepatol. 2024 Jun.

. 2024 Jun;39(6):1190-1197.

doi: 10.1111/jgh.16537. Epub 2024 Mar 13.

Authors

Affiliations

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.

PMID: 38480009
DOI: 10.1111/jgh.16537

Abstract

Background and aim: The 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.

Methods: A 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.

Results: The 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.

Conclusions: Long-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.

Keywords: ETV; NA; TDF; antigen; antiviral; cohort; fibrosis; hepatocellular carcinoma; liver; prognosis.

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References

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

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

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