Heavy Alcohol Intake and ALDH2 rs671 Polymorphism Linked to HCC Mortality

New research shows patients with hepatitis B virus (HBV)-related cirrhosis who also suffer from heavy alcoholism and aldehyde dehydrogenase 2 gene (ALDH2) rs671 polymorphism are at a significantly higher risk of mortality from hepatocellular carcinoma (HCC).

A team, led by Ming-Chao Tsai, MD, PhD, Division of Hepato-Gastroenterology, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, investigated the link between heavy alcohol intake, ALDH2 rs671 polymorphism, and HBV infection with the development and mortality from HCC in patients with Cirrhosis.

The Conditions

It is uncertain what the role of heavy alcohol intake, ALDH2 rs671 polymorphism, and HBV infections in the development and mortality of HCC.

In the retrospective, cohort study, the investigators examined 1515 patients at 3 tertiary hospitals in Taiwan with cirrhosis with heavy alcoholism and/or an HBV infection between January 2005 and December 2020. Each participant was followed up with through June 30, 2021.

The patient population included 342 participants with concomitant heavy alcoholism with HBV infections, 796 patients with only an HBV infection, and 377 patients with only heavy alcoholism. The mean age was 49.5 years.

The team defined heavy alcohol intake as consuming more than 80 g of ethanol each day for at least 5 years.

The investigators sought primary endpoints of newly developed HCC and secondary endpoints of overall mortality.

Data Collection

The team collected blood samples for ALDH2 rs671 polymorphism analysis for 746 patients and found the 10-year cumulative incidences for HCC and mortality were significantly higher in the HBV cohort with heavy alcoholism than it was for either HBV alone or alcoholism alone.

In addition, heavy alcohol intake and the ALDH2 rs671 genotype (GA/AA) were linked to a significantly increased risk of HCC and mortality for patients with HBV-related cirrhosis.

The factors associated with the risk of HCC for patients with cirrhosis with concomitant HBV infections and alcoholism included baseline serum HBV DNA (aHR, 3.24; 95% CI, 1.43-7.31), antiviral therapy (aHR, 0.15; 95% CI, 0.05-0.39), alcohol intake (aHR, 1.78; 95% CI, 1.02-3.12), abstinence (aHR, 0.32; 95% CI, 0.18-0.59), and ALDH2 rs671 polymorphism (aHR, 5.61; 95% CI, 2.42-12.90).

The main factors associated with an increased risk of mortality included abstinence (aHR, 0.25; 95% CI, 0.16-0.32), ALDH2 rs671 polymorphism (aHR, 1.58; 95% CI, 1.09-2.26), Child-Pugh class B vs A (aHR, 1.43; 95% CI, 1.13-2.25) and class C vs A (aHR, 1.98; 95% CI, 1.18-3.31), serum albumin (aHR, 0.61; 95% CI, 0.43-0.86), and HCC development (aHR, 1.68; 95% CI, 1.12-2.89).

“These findings suggest that heavy alcohol intake and ALDH2 rs671 polymorphism are associated with significantly increased risk of HCC development and mortality in patients with HBV-related cirrhosis,” the authors wrote. “Patients with these risk factors should be monitored closely for HCC.”

The study, “Association of Heavy Alcohol Intake and ALDH2 rs671 Polymorphism With Hepatocellular Carcinoma and Mortality in Patients With Hepatitis B Virus–Related Cirrhosis,” was published online in JAMA Network Open.