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. 2017 Oct 10;8(61):103851-103863.
doi: 10.18632/oncotarget.21804. eCollection 2017 Nov 28.

Interaction and joint effect of ALT and chronic liver disease on liver cancer in type 2 diabetes patients

Tsai-Chung Li  1   2 , Chia-Ing Li  3   4 , Chiu-Shong Liu  3   4   5 , Pao-Hsuan Lin  1 , Wen-Yuan Lin  3   5 , Chih-Hsueh Lin  3   5 , Sing-Yu Yang  1 , Jen-Huai Chiang  6 , Cheng-Chieh Lin  3   4   5
Affiliations

Interaction and joint effect of ALT and chronic liver disease on liver cancer in type 2 diabetes patients

Tsai-Chung Li et al. Oncotarget. .

Abstract

Background: This study examined whether serum alanine transaminase (ALT) and chronic liver diseases were interactively, jointly, or independently associated with hepatocellular carcinoma (HCC) risk in type 2 diabetic patients.

Materials and methods: A retrospective cohort study was conducted in 46,369 Chinese type 2 diabetic patients, aged 30 and older, in National Diabetes Care Management Program in 2002-2004. These data were analyzed by multivariate Cox proportional hazards models.

Results: Mean follow-up period was 8.20 years. Multivariate-adjusted hazard ratios of HCC were 2.85 (95% confidence interval, CI: 2.45-3.31), 3.80 (3.04-4.76), and 3.89 (3.08-4.91) for patients with a level of ALT 40-80, 80-120, and >120 U/L, respectively, compared with patients with a level of ALT < 40 U/L after multivariable adjustment. Significant hazard ratios of HCC for patients with a level of ALT ≥ 40 U/L and alcoholic liver damage, nonalcoholic fatty liver disease, liver cirrhosis, hepatitis B virus and hepatitis C virus infection, or any one of these chronic liver diseases compared with patients with ALT level < 40 U/L and no counterpart comorbidity were observed. Significant effect modifications were observed between ALT level with liver cirrhosis and HBV.

Conclusions: Results suggest significant effect modification and joint associations of ALT ≥ 40 U/L and chronic liver diseases. Diabetes care should provide lifestyle or treatment interventions to manage ALT level, liver cirrhosis and hepatitis B virus infection for reducing burden of HCC.

Keywords: alanine transaminase; cohort study; hepatocellular carcinoma; type 2 diabetes.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Kaplan-Meier cumulative risk for HCC within subgroups defined by ALT level
Figure 2
Figure 2. The adjusted HR of HCC for the effects of ALT>40 and alcoholic liver damage, nonalcoholic fatty liver disease, liver cirrhosis, hepatitis B virus infection, hepatitis C virus infection, and any one of these chronic liver diseases for the entire sample, and stratified by insulin use
ALD: alcoholic liver damage; NAFLD: nonalcoholic fatty liver disease; LC: liver cirrhosis; HBV: hepatitis B virus infection; HCV: hepatitis C virus infection; CLD: chronic liver diseases.
Figure 3
Figure 3. Flowchart of recruitment procedures for the current study
See this image and copyright information in PMC

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