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Item Obesity, Diabetes, Coffee, Tea, and Cannabis Use Alter Risk for Alcohol-Related Cirrhosis in 2 Large Cohorts of High-Risk Drinkers(Wolters Kluwer, 2021) Whitfield, John B.; Masson, Steven; Liangpunsakul, Suthat; Mueller, Sebastian; Aithal, Guruprasad P.; Eyer, Florian; Gleeson, Dermot; Thompson, Andrew; Stickel, Felix; Soyka, Michael; Daly, Ann K.; Cordell, Heather J.; Foroud, Tatiana; Lumeng, Lawrence; Pirmohamed, Munir; Nalpas, Bertrand; Jacquet, Jean-Marc; Moirand, Romain; Nahon, Pierre; Naveau, Sylvie; Perney, Pascal; Haber, Paul S.; Seitz, Helmut K.; Day, Christopher P.; Mathurin, Philippe; Morgan, Timothy R.; Seth, Devanshi; GenomALC Consortium; Medicine, School of MedicineIntroduction: Sustained high alcohol intake is necessary but not sufficient to produce alcohol-related cirrhosis. Identification of risk factors, apart from lifetime alcohol exposure, would assist in discovery of mechanisms and prediction of risk. Methods: We conducted a multicenter case-control study (GenomALC) comparing 1,293 cases (with alcohol-related cirrhosis, 75.6% male) and 754 controls (with equivalent alcohol exposure but no evidence of liver disease, 73.6% male). Information confirming or excluding cirrhosis, and on alcohol intake and other potential risk factors, was obtained from clinical records and by interview. Case-control differences in risk factors discovered in the GenomALC participants were validated using similar data from 407 cases and 6,573 controls from UK Biobank. Results: The GenomALC case and control groups reported similar lifetime alcohol intake (1,374 vs 1,412 kg). Cases had a higher prevalence of diabetes (20.5% (262/1,288) vs 6.5% (48/734), P = 2.27 × 10-18) and higher premorbid body mass index (26.37 ± 0.16 kg/m2) than controls (24.44 ± 0.18 kg/m2, P = 5.77 × 10-15). Controls were significantly more likely to have been wine drinkers, coffee drinkers, smokers, and cannabis users than cases. Cases reported a higher proportion of parents who died of liver disease than controls (odds ratio 2.25 95% confidence interval 1.55-3.26). Data from UK Biobank confirmed these findings for diabetes, body mass index, proportion of alcohol as wine, and coffee consumption. Discussion: If these relationships are causal, measures such as weight loss, intensive treatment of diabetes or prediabetic states, and coffee consumption should reduce the risk of alcohol-related cirrhosis.