Interaction Between Alcohol Use and Metabolic Risk Factors for Liver Disease: A Critical Review of Epidemiological Studies

Abstract

Coexistence of alcohol use and metabolic risk-the 2 commonest population risk factors for nonviral chronic liver disease-is a growing concern. Clinical evidence and mechanistic evidence point to considerable supraadditive interaction effects for the development and progression of chronic liver disease between hazardous alcohol use and metabolic abnormalities including obesity, diabetes, and the metabolic syndrome (MetS). Intermittent binge drinking once monthly or more often seems to be associated with progression of liver disease even when average alcohol intake is within the currently allowed limits for a diagnosis of nonalcoholic fatty liver disease (NAFLD), and supraadditive interaction between binge drinking and the MetS has been reported. There are contradictory findings regarding the association between low alcohol use and liver steatosis, but, clearly, the mechanisms of alcoholic hepatotoxicity extend beyond simple fat accumulation. The presence of liver steatosis seems to amplify alcoholic hepatotoxicity. Recent longitudinal studies of NAFLD subjects report low alcohol use associated with both increased fibrosis progression and an elevated risk for liver cancer and severe liver disease. There is no clear safe limit of alcohol intake in the presence of NAFLD or metabolic risk. The interaction effects between alcohol and metabolic dysfunction merit increased attention in public health policy, individual counseling, and risk stratification. Based on current evidence, a strict dichotomization of liver disease into either pure alcoholic or nonalcoholic may be inappropriate.

MAFLD identifies patients with significant hepatic fibrosis better than NAFLD

“…Consistently, a recent Korean cohort study demonstrated that 1‐9.9 g/day of alcohol intake is associated with an increased risk of worsening hepatic fibrosis indices in patients with NAFLD 33 . Adding to these data, an interaction between the presence of metabolic dysfunction and even mild alcohol intake on the risk of advanced hepatic fibrosis has been reported 34,35 …”

Natural History of NAFLD

“…Other studies suggested that, compared to lifetime abstainers, NAFLD patients with low alcohol consumption have significantly increased risk of HCC [ 53 ], cirrhosis decompensation (hazard ratio 1.7) or death/liver transplantation (hazard ratio 2.3) [ 54 ]. The deleterious effect of alcohol in patients with NAFLD is further accentuated by the interaction with the metabolic risk factors, in particular obesity (the risk fraction for liver related outcomes attributable to the interaction between the amount of alcohol and obesity varies between 25% and 70%) [ 55 ]. The pattern of drinking significantly impacts the future risk of liver damage—higher drinking frequency protects from steatosis while binge drinking is positively associated with significant liver damage [ 56 ].…”

“…The pattern of drinking significantly impacts the future risk of liver damage—higher drinking frequency protects from steatosis while binge drinking is positively associated with significant liver damage [ 56 ]. Some studies also suggested that the type of alcoholic beverages differently impacts the severity of the liver damage: consuming 2 drinks/day of non-wine beverage doubles the risk for advanced liver disease compared to lifetime abstainers [ 55 , 57 ]. Most of the studies report a J-shaped relationship between the amount of alcohol and overall mortality, with 20% decrease in mortality risk in patients with <10g/day alcohol consumption compared with abstainers.…”

“…These benefits are mainly due to reduction in cardiovascular mortality [ 57 ]. However, drinking ≥1.5 drinks/day was associated with worse outcomes in most of the studies [ 55 , 58 ].…”

Impact of body mass and alcohol consumption on all‐cause and liver mortality in 240 000 adults in the United States

“…As for chronic liver disease, in particular liver cirrhosis, there are established pathways via heavy drinking [9] and obesity [10], but there are indications that both pathways interact [9]. If we use BMI as the indicator for obesity, there have been four longitudinal cohorts studied on a potential interaction in predicting liver hospitalisations or mortality [11–14], all with large sample sizes (up to more than 1.2 million participants in the million women study) [13].…”