Heavy alcohol use is the most common etiology of alcoholic liver disease (ALD). The wide spectrum of ALD ranges from alcoholic steatosis to steatohepatitis, fibrosis, and cirrhosis. It has been estimated that approximately 50% of cirrhosis-related deaths are due to alcohol use in developed countries. Most patients with ALD do not develop cirrhosis even with long-term alcohol use. However, several factors that can contribute in the progression of disease include gender, ethnicity, genetic variants, viral hepatitis, and obesity.

Gender

Observations suggest that women are likely to use alcohol less than men; hence, have a lower risk for AUD in comparison to men. National surveys have observed alcoholic use disorder (AUD) prevalence to be three-fold greater for men than women in the 2001e2002 survey and two-fold greater in the 2012e2013 survey. However, in spite of lower levels of alcohol intake, women are more vulnerable to the hepatotoxic effects of alcohol. The reduced gastric alcohol breakdown in women permits larger amounts of alcohol to enter the bloodstream and increases alcohol bioavailability.

Drinking pattern as a risk for ALD

The last decade has shown a paradigm shift in high-risk drinking patterns, such as heavy drinking and binge drinking. Binge drinking is defined as drinking episodes of five or more drinks in men, or four or more drinks in women, is highly prevalent. Studies have shown that acute alcohol intoxication and repeated binge drinking can increase intra- and extrahepatic changes that worsen liver injury, including Kupffer cell activation, increased intestinal permeability, elevated cytokine production, increased oxidative stress, mitochondrial dysfunction, and hepatic apoptosis.

Genetic variants

Many common diseases exhibit heritable traits that can provide protective or susceptibility effects. It has been observed that Hispanics are more prone to ALD, and few studies reported that alcoholic cirrhosis prevalence was increased in monozygotic in contrast to dizygotic twins. Other genes such as PNPLA3, MBOAT7 and TM6SF2 variants can also increase the risk for alcoholic cirrhosis. On the contrary, a study has shown that a variant of hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) is linked to reduced alcoholic cirrhosis.

Obesity

In view of the rising prevalence of obesity and metabolic syndrome, weight control is significant cause of concern globally.  The earliest derangement in the ALD spectrum is steatosis, an excessive accumulation of triglycerides in hepatocytes, and almost 90% of alcoholics have histological evidence of fatty liver. Obesity and high alcohol intake synergistically elevated liver enzymes, raising serum alanine aminotransferase (ALT) and aspartate transaminase (AST) levels 8.9- and 21-fold, respectively.

Hepatitis C virus (HCV)

Epidemiological surveys have estimated that 170 million people are infected with HCV globally, and chronic HCV infection is a significant cause of chronic liver disease. Alcohol intake negatively alters the course and outcome of HCV infection. Another trial reported dose-dependent increase in liver injury at even lower alcohol intake among patients with HCV, as a little quantity of 20 g per day in women and 30 g per day in men increased histological activity and fibrosis in these patients. Additionally, alcohol intake increases viremia in patients with HCV.

Source: Ohashi K, Pimienta M, Seki E. Alcoholic liver disease: A current molecular and clinical perspective. Liver Res. 2018;2(4):161-172.