Pretreatment gamma-glutamyl transferase predicts mortality in patients with chronic hepatitis B treated with nucleotide/nucleoside analogs.
GGT
HBV
NA
mortality
treatment
Journal
The Kaohsiung journal of medical sciences
ISSN: 2410-8650
Titre abrégé: Kaohsiung J Med Sci
Pays: China (Republic : 1949- )
ID NLM: 100960562
Informations de publication
Date de publication:
27 Oct 2023
27 Oct 2023
Historique:
revised:
18
09
2023
received:
23
08
2023
accepted:
02
10
2023
pubmed:
27
10
2023
medline:
27
10
2023
entrez:
27
10
2023
Statut:
aheadofprint
Résumé
Elevated serum gamma-glutamyl transferase (GGT) levels are associated with chronic hepatitis B (CHB)-related hepatocellular carcinoma. However, their role in predicting mortality in patients with CHB treated with nucleotide/nucleoside analogs (NAs) remains elusive. Altogether, 2843 patients with CHB treated with NAs were recruited from a multinational cohort. Serum GGT levels before and 6 months (Month-6) after initiating NAs were measured to explore their association with all-cause, liver-related, and non-liver-related mortality. The annual incidence of all-cause mortality was 0.9/100 person-years over a follow-up period of 17,436.3 person-years. Compared with patients who survived, those who died had a significantly higher pretreatment (89.3 vs. 67.4 U/L, p = 0.002) and Month-6-GGT levels (62.1 vs. 38.4 U/L, p < 0.001). The factors associated with all-cause mortality included cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 2.66/1.92-3.70, p < 0.001), pretreatment GGT levels (HR/CI: 1.004/1.003-1.006, p < 0.001), alanine aminotransferase level (HR/CI: 0.996/0.994-0.998, p = 0.001), and age (HR/CI: 1.06/1.04-1.07, p < 0.001). Regarding liver-related mortality, the independent factors included cirrhosis (HR/CI: 4.36/2.79-6.89, p < 0.001), pretreatment GGT levels (HR/CI: 1.006/1.004-1.008, p < 0.001), alanine aminotransferase level (HR/CI: 0.993/0.990-0.997, p = 0.001), age (HR/CI: 1.03/1.01-1.05, p < 0.001), and fatty liver disease (HR/CI: 0.30/0.15-0.59, p = 0.001). Pretreatment GGT levels were also independently predictive of non-liver-related mortality (HR/CI: 1.003/1.000-1.005, p = 0.03). The results remained consistent after excluding the patients with a history of alcohol use. A dose-dependent manner of <25, 25-75, and >75 percentile of pretreatment GGT levels was observed with respect to the all-cause mortality (trend p < 0.001). Pretreatment serum GGT levels predicted all-cause, liver-related, and non-liver-related mortality in patients with CHB treated with NAs.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Kaohsiung Medical University
ID : KMUH109-9R05
Organisme : Kaohsiung Medical University
ID : MOST 111-2314-B-037-069-MY2
Organisme : Kaohsiung Medical University Hospital
ID : KMUH110-0M03
Organisme : Kaohsiung Medical University Hospital
ID : KMUH110-0M06
Organisme : Kaohsiung Medical University Hospital
ID : KMHK-DK(C)111004
Organisme : Kaohsiung Medical University Hospital
ID : KMUH-DK()109005~1
Organisme : Kaohsiung Medical University Hospital
ID : KMUH-DK(B)111002-1
Organisme : Kaohsiung Medical University Hospital
ID : KMHK-DK(C)111006
Organisme : Ministry of Health and Welfare, Taiwan
ID : MOHW111-TDU-B-221-014007
Informations de copyright
© 2023 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.
Références
GBD 2019 Hepatitis B Collaborators. Global, regional, and national burden of hepatitis B, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Gastroenterol Hepatol. 2022;7:796-829.
Bixler D, Zhong Y, Ly KN, Moorman AC, Spradling PR, Teshale EH, et al. Mortality among patients with chronic hepatitis B infection: the Chronic Hepatitis Cohort Study (CHeCS). Clin Infect Dis. 2019;68:956-963.
Zhou K, Dodge JL, Grab J, Poltavskiy E, Terrault NA. Mortality in adults with chronic hepatitis B infection in the United States: a population-based study. Aliment Pharmacol Ther. 2020;52:382-389.
Si J, Yu C, Guo Y, Bian Z, Meng R, Yang L, et al. Chronic hepatitis B virus infection and total and cause-specific mortality: a prospective cohort study of 0.5 million people. BMJ Open. 2019;9:e027696.
Alavi M, Grebely J, Hajarizadeh B, Amin J, Larney S, Law MG, et al. Mortality trends among people with hepatitis B and C: a population-based linkage study, 1993-2012. BMC Infect Dis. 2018;18:215.
Chen VL, Yeh ML, Le AK, Jun M, Saeed WK, Yang JD, et al. Anti-viral therapy is associated with improved survival but is underutilised in patients with hepatitis B virus-related hepatocellular carcinoma: real-world east and west experience. Aliment Pharmacol Ther. 2018;48:44-54.
Nguyen MH, Wong G, Gane E, Kao JH, Dusheiko G. Hepatitis B virus: advances in prevention, diagnosis, and therapy. Clin Microbiol Rev. 2020;33:e00046-19.
Whitfield JB. Gamma glutamyl transferase. Crit Rev Clin Lab Sci. 2001;38:263-355.
Kunutsor SK. Gamma-glutamyltransferase-friend or foe within? Liver Int. 2016;36:1723-1734.
Koenig G, Seneff S. Gamma-glutamyltransferase: a predictive biomarker of cellular antioxidant inadequacy and disease risk. Dis Markers. 2015;2015:818570.
Hu G, Tuomilehto J, Pukkala E, Hakulinen T, Antikainen R, Vartiainen E, et al. Joint effects of coffee consumption and serum gamma-glutamyltransferase on the risk of liver cancer. Hepatology. 2008;48:129-136.
Huang CF, Jang TY, Jun DW, Ahn SB, An J, Enomoto M, et al. On-treatment gamma-glutamyl transferase predicts the development of hepatocellular carcinoma in chronic hepatitis B patients. Liver Int. 2022;42:59-68.
Huang CF, Yeh ML, Tsai PC, Hsieh MH, Yang HL, Hsieh MY, et al. Baseline gamma-glutamyl transferase levels strongly correlate with hepatocellular carcinoma development in non-cirrhotic patients with successful hepatitis C virus eradication. J Hepatol. 2014;61:67-74.
Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10:1-98.
Chien RN, Kao JH, Peng CY, Chen CH, Liu CJ, Huang YH, et al. Taiwan consensus statement on the management of chronic hepatitis B. J Formos Med Assoc. 2019;118:7-38.
Drafting Committee for Hepatitis Management Guidelines and the Japan Society of Hepatology. JSH Guidelines for the management of hepatitis B virus infection. Hepatol Res. 2014;44(Suppl S1):1-58.
Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol. 2019;25:93-159.
Ziol M, Handra-Luca A, Kettaneh A, Christidis C, Mal F, Kazemi F, et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology. 2005;41:48-54.
Saadeh S, Younossi ZM, Remer EM, Gramlich T, Ong JP, Hurley M, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002;123:745-750.
Wong MCS, Huang JLW, George J, Huang J, Leung C, Eslam M, et al. The changing epidemiology of liver diseases in the Asia-Pacific region. Nat Rev Gastroenterol Hepatol. 2019;16:57-73.
Stepanova M, Rafiq N, Younossi ZM. Components of metabolic syndrome are independent predictors of mortality in patients with chronic liver disease: a population-based study. Gut. 2010;59:1410-1415.
Mallet V, Hamed K, Schwarzinger M. Prognosis of patients with chronic hepatitis B in France (2008-2013): a nationwide, observational and hospital-based study. J Hepatol. 2017;66:514-520.
Aberkane H, Stoltz JF, Galteau MM, Wellman M. Erythrocytes as targets for gamma-glutamyltranspeptidase initiated pro-oxidant reaction. Eur J Haematol. 2002;68:262-271.
Aberg F, Luukkonen PK, But A, Salomaa V, Britton A, Petersen KM, et al. Development and validation of a model to predict incident chronic liver disease in the general population: the CLivD score. J Hepatol. 2022;77:302-311.
Strasak AM, Rapp K, Brant LJ, Hilbe W, Gregory M, Oberaigner W, et al. Association of gamma-glutamyltransferase and risk of cancer incidence in men: a prospective study. Cancer Res. 2008;68:3970-3977.
Ho FK, Ferguson LD, Celis-Morales CA, Gray SR, Forrest E, Alazawi W, et al. Association of gamma-glutamyltransferase levels with total mortality, liver-related and cardiovascular outcomes: a prospective cohort study in the UK Biobank. eClinicalMedicine. 2022;48:101435.
Eminler AT, Irak K, Ayyildiz T, Keskin M, Kiyici M, Gurel S, et al. The relation between liver histopathology and GGT levels in viral hepatitis: more important in hepatitis B. Turk J Gastroenterol. 2014;25:411-415.
Huang R, Yang CC, Liu Y, Xia J, Su R, Xiong YL, et al. Association of serum gamma-glutamyl transferase with treatment outcome in chronic hepatitis B patients. World J Gastroenterol. 2015;21:9957-9965.
Zhao Z, Zhu Y, Ni X, Lin J, Li H, Zheng L, et al. Serum GGT/ALT ratio predicts vascular invasion in HBV-related HCC. Cancer Cell Int. 2021;21:517.
Banderas DZ, Escobedo J, Gonzalez E, Liceaga MG, Ramirez JC, Castro MG. Gamma-glutamyl transferase: a marker of nonalcoholic fatty liver disease in patients with the metabolic syndrome. Eur J Gastroenterol Hepatol. 2012;24:805-810.
Fujii H, Doi H, Ko T, Fukuma T, Kadono T, Asaeda K, et al. Frequently abnormal serum gamma-glutamyl transferase activity is associated with future development of fatty liver: a retrospective cohort study. BMC Gastroenterol. 2020;20:217.
Chung GE, Jeong SM, Cho EJ, Yoo JJ, Cho Y, Lee KN, et al. Association of fatty liver index with all-cause and disease-specific mortality: a nationwide cohort study. Metabolism. 2022;133:155222.
Peleg N, Issachar A, Sneh Arbib O, Cohen-Naftaly M, Braun M, Leshno M, et al. Liver steatosis is a strong predictor of mortality and cancer in chronic hepatitis B regardless of viral load. JHEP Rep. 2019;1:9-16.
Li J, Yang HI, Yeh ML, Le MH, Le AK, Yeo YH, et al. Association between fatty liver and cirrhosis, hepatocellular carcinoma, and hepatitis B surface antigen Seroclearance in chronic hepatitis B. J Infect Dis. 2021;224:294-302.
Sung KC, Ryu S, Kim BS, Cheong ES, Park DI, Kim BI, et al. Gamma-glutamyl transferase is associated with mortality outcomes independently of fatty liver. Clin Chem. 2015;61:1173-1181.