Binge drinking, genetic predisposition linked to sixfold higher risk for cirrhosis
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Key takeaways:
- Those with greater daily consumption had an increased risk for both alcohol-related cirrhosis and alcoholic hepatitis.
- The risk for developing cirrhosis “increased monotonically” with polygenic risk score.
Heavy binge drinking and high polygenic risk score were associated with a sixfold higher relative excess risk for alcohol-related cirrhosis, with the presence of diabetes mellitus further increasing the risk, researchers reported.
“Many studies that look into the relationship between liver disease and alcohol focus on the volume of alcohol consumed,” Linda Ng Fat, MSc, PhD, senior research fellow in epidemiology and public health at University College London, said in a university press release. “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.”
Fat continued: “The other key finding was that the more risk factors involved, the higher the ‘excess risk’ due to the interaction of these factors.”
To investigate the extent to which drinking patterns and genetic factors are associated with the risk for alcohol-related cirrhosis (ARC) and alcoholic hepatitis (AH), researchers analyzed data from 312,599 participants in the UK Biobank cohort. Overall, 20% of the cohort drank within the daily limits (< 24 g/day for women; < 32 g/day for men), 42% drank above daily limits (≥ 24 g/day; ≥ 32 g/day), 23% were binge drinkers (≥ 48 g/day to < 72 g/day; ≥ 64 g/day to < 96 g/day) and 15% were heavy binge drinkers (≥ 72 g/day; ≥ 96 g/day for men).
Fat and colleagues noted binge and heavy binge drinkers were more likely to be younger (68.7 years and 67.4 years, respectively, vs. 69.4 years) and male (55% and 63% vs. 51%) compared with the whole cohort.
Over a median follow-up of 12.6 years, there were 734 cases of ARC and 136 cases of AH. Factors associated with an increased risk for liver disease included male sex (78% ARC and 77% AH, respectively, vs. 51% control), current smoking status (33% and 32% vs. 10%) and less physical activity (53% and 50% vs. 35%), as well as greater daily alcohol consumption (71% vs. 30%).
Binge drinking
Models using only observational data confirmed an increased risk for both ARC and AH among those with daily greater consumption.
For ARC, those drinking above the daily limits but below binge levels had an HR of 1.33 (95% CI, 0.96-1.85) which increased for both binge (HR = 2.37; 95% CI, 1.71-3.27) and heavy binge drinking (HR = 3.85; 95% CI, 2.79-5.31).
Researchers noted a similar pattern for AH with binge (HR = 5.16; 95% CI, 1.82-14.65) and heavy binge drinking (HR = 9.38; 95% CI, 3.34-26.37).
Polygenic risk score
Researchers also reported that the risk for developing ARC “increased monotonically” with rising polygenic risk score (PRS), noting those with middle (HR = 1.6; 95% CI, 1.24-2.07) and high PRS (HR = 3.51; 95% CI, 2.7-4.55) were at greater risk compared with those who had a low PRS. The association between PRS and AH did not reach significance.
Analysis further demonstrated that as PRS increased within each alcohol consumption group, there was higher risk for ARC, with the “most marked” effect among those in the heavy binge drinking group (low PRS: HR = 3.53; 95% CI, 1.35-9.19 vs. highest PRS: HR = 12.82; 95% CI, 5.21-31.52).
The relative excess risk due to interaction (RERI) was 6.07 (95% CI, 0.2-11.94) for the presence of heavy binge drinking and PRS, researchers noted.
Interaction with diabetes mellitus
Diabetes mellitus status “significantly” increased the risk for ARC across all consumption groups and PRS categories, with cumulative interactions reported with heavy binge drinking and high PRS (RERI = 4.69; 95% CI, 0.5-8.88 and 4.83; 95% CI, 0.99-8.67, respectively).
Further, the excess risk due to the presence of heavy binge drinking, high PRS and diabetes produced a total RERI of 24.39 (95% CI, –0.24 to 49.02).
“Only one in three people who drink at high levels go on to develop serious liver disease,” Gautam Mehta, senior study author and principal clinical researcher at University College London, said in the release. “While genetics plays a part, this research highlights that pattern of drinking is also a key factor.”
Mehta continued: “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.”
Reference:
- Pattern of alcohol intake more accurate indicator of liver disease risk than overall consumption. https://medicalxpress.com/news/2023-12-pattern-alcohol-intake-accurate-indicator.html#google_vignette. Published Dec. 14, 2023. Accessed Dec. 14, 2023.
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