Metabolic Syndrome Could Worsen Damaging Effects of Alcohol Use on Liver


Despite stable rates of heavy alcohol use, deaths from alcohol-associated liver damage have risen in the US. A new study suggests an increase in the damaging effects of alcohol use in people with metabolic syndrome could be driving this apparent increase.

Brian Lee, MD, MAS | Credit: Keck School of Medicine of USC

Brian Lee, MD, MAS
Credit: Keck School of Medicine of USC

An analysis of nationwide survey data recorded over a 20-year period suggests deaths from alcohol-associated liver disease increased by more than in the United States by more than 30% from 1998-2018, despite alcohol use, including heavy drinking, remaining stable or declining during that time period.

Spurred by a surge in mortality from alcohol-associated liver disease during the study period, investigators from the Keck School of Medicine sought to examine the role of metabolic syndrome in this phenomenon and determined people with metabolic syndrome may be more susceptible to advanced liver damage as a result of heavy alcohol use relative to their counterparts without heavy alcohol use.

“Our research suggests that metabolic syndrome and alcohol interact in such a way that they multiply the effect of alcohol on the liver, more than doubling the risk of advanced liver disease among heavy drinkers,” said lead investigator Brian P. Lee, MD, MAS, a hepatologist and liver transplant specialist with Keck School of Medicine of the University of Southern California. “Drinking is harmful to the liver, but especially so for this segment of the population.”

For the purpose of analysis, heavy alcohol use was defined as average alcohol use in the past months 12 months higher 28 grams per day for women or 42 grams per day for men. Investigators defined metabolic syndrome using the National Cholesterol Education Program’s Adult Treatment Panel III classification. Of note, this definition requires patients to meet at least 3 of the following criteria: waist circumference larger than 102 cm for men or 88 cm for women, serum triglyceride level of at least 1.7 mmol/L, HDL-C level less than 1 mmol/L for men or less than 1.3 mmol/L for women, blood pressure of at least 130/85 mmHg or receiving antihypertensive medications, or fasting plasma glucose level of at least 5.6 mmol/L or receiving diabetes medications.

Investigators estimated the survey-weighted prevalence of 6 key subgroups for each 4-year interval based on alcohol use and metabolic syndrome. These groups were categorized as no alcohol use without metabolic syndrome, nonheavy alcohol use without metabolic syndrome, heavy alcohol use without metabolic syndrome, no alcohol use without metabolic syndrome, and heavy alcohol use with metabolic syndrome. Investigators estimated marginally adjusted probabilities of advanced liver disease for each subgroup using logistic regression with adjustment for age, sex, and active smoking.

From NHANES, investigators obtained information related to 42,224 respondents. Upon analysis, results indicated the survey-weight prevalence of people with metabolic syndrome with nonheavy alcohol use increased from 18.7% (95% CI, 17.1 to 20.3) from 1999-2002 to 27.5% (95% CI, 25.9 to 29.2) from 2015-2018. In contrast, the prevalence of all other subgroups remained stable or decreased. Further analysis of adjusted probability of advanced liver disease within each group increased throughout the study period among all subgroups indicated the absolute highest absolute change was observed among the heavy alcohol use subgroups in those with (1999-2002: 3.0 percentage points [95% CI, 0.0 to 7.0]; 2015-2018: 10.8 percentage points [95% CI, 2.4 to 9.1]; absolute difference, 7.8 percentage points [95% CI, −1.4 to 17.1]).

“Our study indicates that these conditions may often coexist, and it is in patients’ best interest to address both issues,” Lee added. “It’s also important for people with metabolic syndrome to realize they may be at an increased likelihood of advanced liver disease, and to monitor their drinking accordingly.”


  1. Lee BP, Dodge JL, Mack WJ, Leventhal AM, Terrault NA. National Trends in Alcohol Use, Metabolic Syndrome, and Liver Disease From 1999 to 2018 [published online ahead of print, 2023 May 9]. Ann Intern Med. 2023;10.7326/M23-0518. doi:10.7326/M23-0518
  2. Keck Medicine of USC. Heavy drinking poses even greater risk for one in three Americans. May 10, 2023. Accessed May 12, 2023.
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