| Impact of components of metabolic syndrome on long-term outcomes of CHB with nucleos(t)ide analogue treatment |
| Rui Huang1,2,3, Dae Won Jun4,5, Hidenori Toyoda6, Yao-Chun Hsu7, Huy Trinh8, Akito Nozaki9, Toru Ishikawa10, Tsunamasa Watanabe11, Haruki Uojima12,13, Daniel Q. Huang14,15, Takashi Honda16, Yasuhito Tanaka17,18, Philip Vutien19, Sebastián Marciano20,21, Hiroshi Abe22, Masaru Enomoto23,24, Masanori Atsukawa25, Hirokazu Takahashi26,27, Kunihiko Tsuji28, Koichi Takaguchi29, Pei-Chien Tsai30, Chia-Yen Dai30,31, Jee-Fu Huang30,31, Chung-Feng Huang30,31, Ming-Lun Yeh30,31, Eileen Yoon4,5, Sung Eun Kim32, Sang Bong Ahn33, Gi-Ae Kim34, Jang Han Jung35, Soung Won Jeong36, Hyunwoo Oh37, Cheng-Hao Tseng38, Masatoshi Ishigami16, Angela Chau1, Mayumi Maeda1, Satoshi Yasuda6, Makoto Chuma39, Takanori Ito16, Keigo Kawashima17, Joanne Kimiko Liu1,19, Adrian Gadano20,21, Ritsuzo Kozuka23, Norio Itokawa25, Kaori Inoue26, Tomonori Senoh29, Jie Li2,3, Wan-Long Chuang30,31, Ramsey Cheung1,40, Chao Wu2,3, Ming-Lung Yu30,31,41, Mindie H. Nguyen1,42 |
1Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA
2Department of Infectious Disease, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
3Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, China
4Department of Internal Medicine, Hanyang University, College of Medicine, Seoul, South Korea
5Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul, South Korea
6Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
7Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
8San Jose Gastroenterology, San Jose, CA, USA
9Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
10Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
11Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, Japan
12Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan
13Genome Medical Sciences Project, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan
14Division of Gastroenterology and Hepatology, National University Hospital, Singapore
15Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
16Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
17Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
18Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
19Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA
20Jefe de Hepatología - Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
21Jefe de la Sub-secretaria de Investigación Clínica - Instituto Universitario Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
22Division of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Chiba, Japan
23Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
24Department of Transfusion Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
25Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
26Liver Center, Saga University Hospital, Saga, Japan
27Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga, Japan
28Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
29Department of Hepatology, Kagawa Prefectural Central Hospital, Kagawa, Japan
30Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
31Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
32Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang-si, South Korea
33Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University College of Medicine, Seoul, South Korea
34Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, South Korea
35Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong-si, South Korea
36Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong-si, South Korea
37Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
38Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Cancer Hospital/I-Shou University, Kaohsiung, Taiwan
39Gastroenterological Center, JCHO Yokohama Hodogaya Central Hospital, Yokohama, Japan
40Gastroenterology and Hepatology, The Palo Alto Veterans Affairs Health Care System, Palo Alto, CA, USA
41School 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
42Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA |
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Received: November 27, 2024 Revised: March 12, 2025 Accepted: March 14, 2025 |
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| ABSTRACT |
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Background
Given the rise of metabolic diseases, we investigated their long-term impact in chronic hepatitis B (CHB) patients receiving nucleos(t)ide analogue (NA).
Methods
We analyzed data from CHB patients who initiated NAs from 30 centers (7 countries/regions). We balanced patient characteristics with and without metabolic disease (diabetes, obesity, dyslipidemia, and hypertension) via propensity-score matching (PSM) to evaluate adverse liver events and motality.
Results
The study included 4,500 CHB patients (54.6% with ≥1 metabolic disease). PSM yielded 909 pairs of patients with balanced characteristics. When stratified by the number of metabolic disease, only patients with ≥2 metabolic diseases had increased cumulative incidence of cirrhosis and overall death (but not HCC or cause-specific death). However, when stratified by the presence of diabetes (regardless of the presence or number of other metabolic diseases), patients with diabetes (vs. those without) had significantly higher cumulative incidence of all outcomes: cirrhosis (P=0.009), HCC (P=0.023), overall, liver-related and non-liver-related death (P<0.001, P=0.026 and P<0.001, respectively). On Cox regression analysis, having ≥2 metabolic diseases was associated with cirrhosis, overall death and non-liver-related death but not HCC and liver-related death, while diabetes was significantly associated with higher risk of all outcomes: cirrhosis (HR=3.75, P=0.004), HCC (HR=2.02, P=0.020), overall, liver-related and non-liver-related death (HR=2.53, P<0.001; HR=2.65, P=0.016; HR=2.38, P<0.001).
Conclusion
Having ≥2 metabolic diseases was associated with significantly higher risk of cirrhosis, overall death and non-liver-related death, but having diabetes as a single metabolic disease was significantly associated with all adverse outcomes including cirrhosis, HCC, overall, liver-related and non-liver-related death. |
| KeyWords:
chronic hepatitis B; metabolic diseases; nucleos(t)ide analogues; hepatocellular carcinoma; death |
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