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On-treatment gamma-glutamyl transferase predicts the development of hepatocellular carcinoma in chronic hepatitis B patients.

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On-treatment gamma-glutamyl transferase predicts the development of hepatocellular carcinoma in chronic hepatitis B patients. Liver international : official journal of the International Association for the Study of the Liver Huang, C., Tyng-Yuan, J., Jun, D. W., Ahn, S. B., An, J., Enomoto, M., Takahashi, H., Ogawa, E., Yoon, E., Jeong, S. W., Shim, J., Jeong, J. Y., Kim, S. E., Oh, H., Kim, H. S., Cho, Y. K., Kozuka, R., Inoue, K., Cheung, K. S., Mak, L. Y., Huang, J., Dai, C., Yuen, M., Nguyen, M. H., Yu, M. 2021

Abstract

BACKGROUND &AIMS: Gamma-glutamyl transferase (GGT) has been predictive of chronic hepatitis C-related hepatocellular carcinoma (HCC) development. Its role in the risk of HCC in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues (NAs) is elusive.METHODS: A total of 2,172 CHB patients from East Asia were randomized into development and validation groups in a 1:2 ratio. Serum GGT levels before and 6 months (M6) after initiating NAs and the potential risk factors were measured. The primary endpoint was HCC development 12 months after NA initiation.RESULTS: The annual incidence of HCC was 1.4/100 person-years in a follow-up period of 11370.7 person-years. The strongest factor associated with HCC development was high M6-GGT levels (>25 U/L; hazard ratio [HR]/95% confidence interval [CI]:3.31/2.02-5.42, P<0.001), followed by cirrhosis (HR/CI: 2.06/1.39-3.06, P<0.001), male sex (HR/CI: 2.01/1.29-3.13, P=0.002), and age (HR/CI: 1.05/1.03-1.17, P<0.001). Among cirrhotic patients, the incidence of HCC did not differ between those with high or low M6-GGT levels (P=0.09). In contrast, among non-cirrhotic patients, the incidence of HCC was significantly higher for those with M6-GGT level >25 U/L than for their counterparts (P<0.001). Cox regression analysis revealed that the strongest factor associated with HCC development in non-cirrhotic patients was high M6-GGT levels (HR/CI: 5.05/2.52-10.16, P<0.001), followed by age (HR/CI: 1.07/1.04-1.09, P<0.001). Non-cirrhotic elderly patients with high M6-GGT levels had a similarly high HCC risk as cirrhotic patients did (P=0.29).CONCLUSIONS: On-treatment serum GGT levels strongly predicted HCC development in CHB patients, particularly non-cirrhotic patients, treated with NAs.

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