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

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 2172 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 11 370.7 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 < .001), followed by cirrhosis (HR/CI: 2.06/1.39-3.06, P < .001), male sex (HR/CI: 2.01/1.29-3.13, P = .002) and age (HR/CI: 1.05/1.03-1.17, P < .001). Among cirrhotic patients, the incidence of HCC did not differ between those with high or low M6-GGT levels (P = .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 < .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 < .001), followed by age (HR/CI: 1.07/1.04-1.09, P < .001). Non-cirrhotic elderly patients with high M6-GGT levels had a similarly high HCC risk as cirrhotic patients did (P = .29).

CONCLUSIONS:

On-treatment serum GGT levels strongly predicted HCC development in CHB patients, particularly non-cirrhotic patients, treated with NAs.

• Authors: Chung-Feng Huang, Tyng-Yuan Jang, Dae Won Jun, Sang Bong Ahn, Jihyun An, Masaru Enomoto, Hirokazu Takahashi, Eiichi Ogawa, Eileen Yoon, Soung Won Jeong, Jae-Jun Shim, Jae Yoon Jeong, Sung Eun Kim, Hyunwoo Oh, Hyoung Su Kim, Yong Kyun Cho, Ritsuzo Kozuka, Kaori Inoue, Ka Shing Cheung, Lung Yi Mak, Jee-Fu Huang, Chia-Yen Dai, Man-Fung Yuen, Mindie H Nguyen, Ming-Lung Yu
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 42 Issue 1 Pg. 59-68 (01 2022) ISSN: 1478-3231 [Electronic] United States
• PMID: 34687130 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• gamma-Glutamyltransferase

Topics

• Aged
• Carcinoma, Hepatocellular
• Hepatitis B, Chronic (complications, drug therapy)
• Humans
• Incidence
• Liver Cirrhosis (complications)
• Liver Neoplasms (etiology)
• Male
• Retrospective Studies
• Risk Factors
• gamma-Glutamyltransferase