Abstract
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. 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. 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. 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.
Highlights
Controls were more likely than cases to have been coffee drinkers during the time they were drinking alcohol heavily, and to have drunk more coffee per day, but there was no significant difference for tea consumption (Table 2)
Regular cannabis use was about three times more common among the controls (27%) than cases (9%) (Table 2) but the proportion decreased with age and the case-control difference was non-significant in patients aged over 60 years (Figure 1(a))
Nor can we be sure that we are seeing a protective effect of wine rather than a harmful effect associated with a preference for other beverages, because the UK Biobank data suggest that a higher proportion of alcohol taken as spirits is associated with higher risk of cirrhosis
Summary
Methods: We conducted a multi-centre case-control study (GenomALC) comparing 1293 cases (with alcohol-related cirrhosis, 75.6% male) and 754 controls (with equivalent alcohol exposure but no evidence of liver disease, 73.6% male). Case-control differences in risk factors discovered in the GenomALC participants were validated using similar data from 407 cases and 6573 controls from UK Biobank. Results: The GenomALC case and control groups reported similar lifetime alcohol intake (1374 versus 1412 kg). Data from UK Biobank confirmed these findings for diabetes, BMI, proportion of alcohol as wine and coffee consumption. Conclusions: If these relationships are causal, measures such as weight loss, intensive treatment of diabetes or pre-diabetic states, and coffee consumption should reduce risk of alcohol-related cirrhosis
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