Heavy Alcoholism, ALDH2 rs671 Polymorphism Associated with Higher Risk of Hepatocellular Carcinoma, Mortality

Heavy alcohol intake and aldehyde dehydrogenase 2 gene (ALDH2) rs671 polymorphism are associated with a significantly increased risk of hepatocellular carcinoma (HCC) development and mortality in patients with hepatitis B virus (HBV)-related cirrhosis, according to a study recently published in JAMA Network Open. Researchers recommend that patients with these risk factors be monitored closely for HCC.

Though high daily alcohol intake has been shown to enhance the progression of cirrhosis and the development of HCC, the roles of heavy alcohol intake, ALDH2 rs671 polymorphism, and HBV infection in the development of HCC and mortality remain uncertain.

Researchers conducted a retrospective cohort study to investigate this association between heavy alcohol intake, ALDH2 rs671 polymorphism, and HBV infection with HCC development and mortality in patients with cirrhosis.

Patients with cirrhosis with heavy alcoholism and/or HBV infection from January 2005 to December 2020 were enrolled in the study. Heavy alcohol intake was defined as consuming more than 8 g of ethanol every day for at least 5 years.

The patients were from 3 tertiary hospitals in Taiwan and were followed through June 30, 2021. Researchers sought to identify newly developed HCC and measure overall mortality.

The cohort included 1515 patients with cirrhosis, including 342 with concomitant heavy alcoholism and HBV infection, 796 with HBV infection alone, and 377 with heavy alcoholism alone. Of these patients, 1277 (84.3%) were men and the mean (SD) age was 49.5 (10.2) years. Blood samples for ALDH2 rs671 polymorphism analysis were collected from 746 patients.

Researchers found that the 10-year cumulative incidences of HCC and mortality were significantly higher in patients with cirrhosis with concomitant HBV infection and alcoholism than in those with HBV infection or alcoholism alone.

Heavy alcohol intake and the ALDH2 rs671 genotype (GA/AA) were found to be associated with significantly increased risk of HCC and mortality in patients with HBV-related cirrhosis. However, the authors note that whether ALDH2 rs671 polymorphism is a risk factor for HCC in patients without alcoholism remains unclear and warrants further study.

In patients with cirrhosis with concomitant HBV infection and alcoholism, factors associated with the risk of HCC were baseline serum HBV, antiviral therapy, alcohol intake, abstinence, and ALDH2 rs671 polymorphism.

Factors found to be associated with increased risk of mortality included abstinence, ALDH2 rs671 polymorphism, Child-Pugh class B vs A and class C vs A, serum albumin, and HCC development. Alcoholism, genetic factors, the severity of disease, and tumor-related factors were all important for mortality.

The data also showed that serum HBV DNA levels are significantly associated with HCC risk. Antiviral therapy was found to be associated with significantly reduced incidence of HCC in patients with cirrhosis with HBV infection and alcoholism.

The results of this study were generally consistent with previous findings. The researchers recommend that patients with cirrhosis and other risk factors be closely followed and aggressively treated to decrease the incidence of HCC and mortality.

The study had some limitations including the retrospective nature and the potential for patients to inaccurately report their alcohol intake during follow up. However, the authors assert that their findings still contribute to the literature on this topic, considering the large, multicenter design and analyses.

Reference

Tsia MC, Yang SS, Lin CC, et al. Association of heavy alcohol intake and ALDH2 rs671 polymorphism with hepatocellular carcinoma and mortality in patients with hepatitis B virus-related cirrhosis. JAMA Netw Open. 2022;5(7):e2223511. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2794544. Published July 25, 2022. Accessed July 27, 2022.