Association of Heavy Alcohol Intake and ALDH2 rs671 Polymorphism With Hepatocellular Carcinoma and Mortality in Patients With Hepatitis B Virus–Related Cirrhosis

Abstract

IMPORTANCEThe role of heavy alcohol intake, aldehyde dehydrogenase 2 gene (ALDH2) rs671 polymorphism, and hepatitis B virus (HBV) infection in hepatocellular carcinoma (HCC) development and mortality remains uncertain. OBJECTIVE To investigate the association of heavy alcohol intake, ALDH2 rs671 polymorphism, and HBV infection with HCC development and mortality in patients with cirrhosis. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study enrolled patients with cirrhosis with heavy alcoholism or/and HBV infection from January 2005 to December 2020. Patients were followed up through June 30, 2021. The current data analysis was performed from August 2021 to April 2022. Patients from 3 tertiary hospitals in Taiwan were enrolled.EXPOSURES Heavy alcohol intake was defined as consuming more than 80 g of ethanol each day for at least 5 years. MAIN OUTCOMES AND MEASURESThe primary end point was newly developed HCC. The secondary end point was overall mortality. RESULTSOf 1515 patients with cirrhosis (342 with concomitant heavy alcoholism and HBV infection, 796 with HBV infection alone, and 377 with heavy alcoholism alone), 1277 (84.3%) were men, and their mean (SD) age was 49.5 (10.2) years; 746 patients had blood samples collected for ALDH2 rs671 polymorphism analysis. 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 alone or alcoholism alone. Heavy alcohol intake and the ALDH2 rs671 genotype (GA/AA) were associated with significantly increased risk of HCC and mortality in patients with HBV-related cirrhosis. In patients with cirrhosis with concomitant HBV infection and alcoholism, factors associated with risk of HCC were baseline serum HBV DNA (adjusted hazard ratio [aHR], 3.24;

Mortality in patients with chronic hepatitis B treated with tenofovir or entecavir: A multinational study

“…Alcohol intake may increase the mortality risk in patients with chronic hepatitis 27 . Heavy drinking has contributed to mortality in a cohort with CHB cirrhosis without antiviral treatment 28 . In this study, we excluded heavy drinkers, and the use of alcohol did not significantly increase the mortality risk.…”

“…27 Heavy drinking has contributed to mortality in a cohort with CHB cirrhosis without antiviral treatment. 28 In this study, we excluded heavy drinkers, and the use of alcohol did not significantly increase the mortality risk. Further studies are required to determine whether alcohol consumption has a dose-dependent effect on mortality in CHB-treated populations.…”

ACG Clinical Guideline: Alcohol-Associated Liver Disease

“…Furthermore, in another prospective cohort study of 1,515 patients with cirrhosis, those with HBV and heavy chronic alcohol use (.80 g of alcohol daily for . 5 years) had a higher incidence of HCC occurring over a 10-year follow-up compared with patients with HBV cirrhosis without heavy alcohol use (crude HR 2.13, 95% CI 1.62-2.81, P , 0.001) (67). Due to various susceptibility factors, individuals with long-term harmful alcohol use are at risk for AH, cirrhosis, and HCC (68).…”

“…For patients with cirrhosis and HBV infection with AUD, higher HBV DNA levels were associated with risk of HCC, while treatment with oral antiviral drugs for HBV infection protected against HCC development (66). Furthermore, in another prospective cohort study of 1,515 patients with cirrhosis, those with HBV and heavy chronic alcohol use (>80 g of alcohol daily for > 5 years) had a higher incidence of HCC occurring over a 10-year follow-up compared with patients with HBV cirrhosis without heavy alcohol use (crude HR 2.13, 95% CI 1.62–2.81, P < 0.001) (67).…”

Literature Review: Pengaruh Enzim ALDH2 dalam Detoksifikasi Alkohol terhadap Sirosis Hati

“…Sebaliknya, pada individu dengan AA homozigot memiliki reaksi merugikan dapat terjadi secara cepat meskipun dengan konsumsi sedikit alkohol (Abe et al, 2015). Penelitian Tsai et al (2022) (Park et al, 2016). Defisiensi ALDH2 juga meningkatkan risiko terjadinya hepatocellular carcinoma pada orang dengan sirosis hati (Seo et al, 2019).…”