Pretreatment gamma-glutamyl transferase predicts mortality in patients with chronic hepatitis B treated with nucleotide/nucleoside analogs.
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Jang Tyng-Yuan, Liang Po-Cheng, Jun Dae Won, Jung Jang Han, Toyoda Hidenori, Wang Chih-Wen, Yuen Man-Fung, Cheung Ka Shing, Yasuda Satoshi, Kim Sung Eun, Yoon Eileen L, An Jihyun, Enomoto Masaru, Kozuka Ritsuzo, Chuma Makoto, Nozaki Akito, Ishikawa Toru, Watanabe Tsunamasa, Atsukawa Masanori, Arai Taeang, Hayama Korenobu, Ishigami Masatoshi, Cho Yong Kyun, Ogawa Eiichi, Kim Hyoung Su, Shim Jae-Jun, Uojima Haruki, Jeong Soung Won, Ahn Sang Bong, Takaguchi Koichi, Senoh Tomonori, Buti Maria, Vargas-Accarino Elena, Abe Hiroshi, Takahashi Hirokazu, Inoue Kaori, Huang Jee-Fu, Chuang Wan-Long, Yeh Ming-Lun, Dai Chia-Yen, Huang Chung-Feng, Nguyen Mindie H, Yu Ming-Lung
Аннотация
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.