Alcohol Consumption Pattern May Be Better Predictor of Liver Disease Than Volume

Gautam Mehta, PhD

Credit: University College London

Binge-pattern drinking, genetic susceptibility, and diabetes mellitus may be important factors for identifying individuals at a greater risk of incident alcohol-related liver disease (ARLD) and implementing targeted interventions, according to findings from a recent study.

Among more than 300,000 actively drinking adults in UK Biobank cohort, binge and heavy binge drinking significantly increased the risk of alcohol-related cirrhosis (ARC), which was further amplified by higher genetic predisposition and presence of diabetes mellitus.¹

Quantity and duration of alcohol intake are among the most significant risk factors for the development of liver disease, which can eventually progress to cirrhosis. However, not all people who drink alcohol develop liver disease, and not all people who drink heavily develop cirrhosis, posing questions as to what other factors may influence the risk of alcohol-related liver disease and eventual cirrhosis.²

“Many studies that look into the relationship between liver disease and alcohol focus on the volume of alcohol consumed. We took a different approach by focusing on the pattern of drinking and found that this was a better indicator of liver disease risk than volume alone. The other key finding was that the more risk factors involved, the higher the ‘excess risk’ due to the interaction of these factors,” said Linda Ng Fat, MSc, senior research fellow in the department of epidemiology and public health at University College London.³

To assess the association between drinking pattern, genetic risk, and diabetes mellitus with the risk of ARC and alcoholic hepatitis (AH), Chengyi Ding, MPH, research associate at University College London, and colleagues collected data from the UK Biobank between 2005 and 2010 from 22 assessment centers for patients who lived within 25 miles of the center and were registered with a general practitioner. Patients with any liver disease or viral hepatitis before baseline were excluded, as well as those who were not current weekly drinkers.¹

From the initial sample of 502,460 UK Biobank participants, 6721 were excluded due to liver disease or viral hepatitis prior to baseline. Of the remaining participants, 342,541 were current weekly drinkers. A further 29,942 patients were excluded due to missing data for physical activity, polygenic risk score, and alcohol intake, resulting in a final cohort of 312,599 participants.¹

The primary endpoint event was first liver-related hospitalization or death due to ARC and the secondary outcome was first hospitalization or death due to AH. Investigators linked baseline data to hospital episode statistics and the national mortality register, which were provided in the UK Biobank dataset.¹

Average daily consumption was calculated by dividing the total weekly grams of alcohol consumed by the midpoint of categorical response to the self-reported alcohol consumption frequency by 6, 3.5, and 1.5, respectively, to estimate an average daily amount. Based on this estimate, standard cut-offs, and definitions for daily and binge consumption, investigators created the following categorical variable parameters: within daily limits (<24 g/day for women, <32 g/day for men), above daily limits but below binge (≥24 g and <48 g/day for women, ≥32 g and <64 g/day for men), binge (≥48 g and <72 g/day units for women, ≥64 g and <96 g/day units for men) and heavy binge (≥72 g/day for women, and ≥96 g/day for men).¹

Participants who drank within limits accounted for 20% of the cohort, and those who drank above limits, binge, or heavy binge accounted for 42%, 23%, and 15% respectively. Binge and heavy binge drinkers were younger than the average (mean age: binge group 68.7 years; heavy binge group 67.4 years; total sample 69.4 years), more likely to be male (binge group 55%; heavy binge group 63%; total sample 51%), reported drinking less frequently during the week, and were more likely to drink without meals.¹

Among the cohort, there were 734 cases of ARC and 136 cases of AH over a median follow-up of 12.6 (interquartile range, 11.9-13.3) years. Investigators noted liver disease cases were significantly more likely to be male (ARC 78% vs control 51% and AH 77% vs control 51%; both P < .001), current smokers (ARC 33% vs control 10% and AH 32% vs. control 10%; P < .001), and to be less active (no physical activity: ARC 53% vs control 35%; P < .001; AH 50% vs control 35%; P = .027). Additionally, greater weekly alcohol intake and daily drinking were significantly associated with risk of liver disease (both P < .001).¹

In models adjusted for total weekly alcohol intake, sex, age, prevalent diabetes mellitus, BMI, and other sociodemographic and behavioral risk factors, greater daily alcohol consumption was associated with an increased risk of both ARC and AH (both P < .001). After accounting for multiple covariates including binge drinking pattern, weekly alcohol intake, diabetes mellitus, and obesity, the risk of developing ARC increased monotonically with increasing polygenic risk score (P < .001). Although a similar trend was observed for AH, investigators noted the association did not reach statistical significance.¹

Within each alcohol consumption group, increasing polygenic risk score led to an increased risk of ARC. This was most notable in the heavy binge group, where polygenic risk score influenced risk of ARC from HR 3.53 (95% CI 1.35, 9.19) in the lowest polygenic risk score group to HR 12.82 (95% CI 5.21, 31.52) in the highest polygenic risk score group. Diabetes status was found to significantly increase risk of ARC across all alcohol consumption groups, and also in all 3 categories of polygenic risk score, after adjustment for sex, age, BMI, and other relevant risk factors.¹

“Only one in three people who drink at high levels go on to develop serious liver disease. While genetics plays a part, this research highlights that pattern of drinking is also a key factor. Our results suggest, for example, that it would be more damaging to drink 21 units over a couple of sessions rather than spread evenly over a week. Adding genetic information, which may be widely used in healthcare over the coming years, allows an even more accurate prediction of risk,” said Gautam Mehta, PhD, principal clinical researcher at University College London.³

References:

1. Ding C, Ng Fat L, Britton A, et al. Binge-pattern alcohol consumption and genetic risk as determinants of alcohol-related liver disease. Nat Commun 14, 8041 (2023). https://doi.org/10.1038/s41467-023-43064-x
2. Patel R, Mueller M. Alcoholic Liver Disease. StatPearls. July 13, 2023. Accessed December 21, 2023. https://www.ncbi.nlm.nih.gov/books/NBK546632/
3. University College London. Pattern of alcohol intake more accurate indicator of liver disease risk than overall consumption. EurekAlert! December 14, 2023. Accessed December 21, 2023. https://www.eurekalert.org/news-releases/1010765