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The correlation between ALDH2 rs671 polymorphism and clinical prognosis in alcoholic liver disease-related
Chih-Jan Ko1,2,3, Wen-Lung Wang4,5, Hung-Yu Lin5,6
1Department of Public Health, China Medical University Taichung, Taiwan.
Abstract:
Whether the aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism predicts clinical prognosis in alcoholic liver disease (ALD)-related hepatocellular carcinoma (HCC) after hepatectomy remains unclear. Hence, this study aims to investigate the association between ALDH2 rs671 polymorphism and HCC recurrence and mortality in patients with ALD-related HCC who underwent hepatectomy. We also explored the risk factors for HCC recurrence and mortality in this population of patients. This retrospective cohort study enrolled 238 ALD-related HCC patients underwent hepatectomy from 2011 to 2022 at the E-Da Hospital, I-Shou University. Data analyses were finalized on October, 2023. Alcoholism was defined as consuming over 20 g of ethanol each day for at least 5 years. Patients with HBsAg-positive or/and HCV-positive status were excluded. ALDH2 rs671 polymorphism was analyzed. The endpoint was HCC recurrence and overall mortality. Of the 238 patients enrolled, 196 (82.4%) were men, and the mean (SD) age was 62.3 (10.2) years. HCC recurrence occurred in 70 patients, and 64 patients died. ALDH2 rs671 polymorphism was significantly associated with HCC recurrence and mortality. The 10-year cumulative HCC recurrence and mortality rates were significantly higher in patients with the ALDH2 rs671 genotype GA/AA relative to those with the ALDH2 rs671 genotype GG. In the Cox proportional analyses, the ALDH2 rs671 genotypes GA/AA (hazard ratio [HR]: 2.66, 95% confidence interval [CI]: 1.59-4.43, P = 0.000) and AST ≥ 40 IU/L (HR: 1.93, 95% CI: 1.18-3.17, P = 0.009) were significantly associated with increased HCC recurrence. Furthermore, the ALDH2 rs671 genotype GA/AA (HR: 2.02, 95% CI: 1.17-3.49, P = 0.012) and age ≥ 65 years (HR: 1.67, 95% CI: 1.01-2.78, P = 0.048) were significantly associated with increased mortality. In conclusion, the ALDH2 rs671 genotype GA/AA is significantly associated with unfavorable clinical prognosis in ALD-related HCC after hepatectomy.
