| Summary: | Alcoholic liver disease (ALD) is a potentially fatal complication of heavy drinking, yet only a minority of heavy drinkers develop ALD. This variable susceptibility has been thought to be genetic in origin, but of the many candidate genes suggested, based on association studies, virtually none have been independently confirmed. Our hypothesis is that genetic predisposition to ALD is modest and that environmental cofactors (as early as during intrauterine life) play an important role in predisposing heavy drinkers to ALD. The aims of this research are: (a) to evaluate familial predisposition to ALD, (b) to assess the association of decompensated ALD (D-ALD) with several, previously poorly characterised potential environmental factors using a case-control strategy, (c) to identify (“capture”) every case of D-ALD in Sheffield over a defined time period, through detailed analysis of overlapping electronic databases and thus assess prevalence, incidence, demographics and geographical distribution. Case-Control Study: We recruited two cohorts of heavy drinkers (> 60 units/week (male) and 40 units/week (female)) in Sheffield between 1998 and 2010. Cases had D-ALD (Child’s grade B or C) while controls had no evidence of serious liver disease. Data were collected regarding: 1) drinking behaviour and presence of liver disease in relatives, 2) lifetime alcohol intake, total and individual beverages, 3) cigarette consumption and 4) early life events, including prematurity and birth weight (maternal recall, validated by available records). Family history results show ALD and liver disease relative risk in relatives of cases vs controls to be 1.1 to 1.3, suggesting that familial predisposition to ALD is modest. There were no significant differences between the two cohorts in regard to birth weight, prematurity, mothers’ smoking in pregnancy or subjects’ current or past smoking. Lifetime cigarette consumption was negatively associated with risk of ALD. Capture Study: We have proposed a system for use in identifying potential cases of ALD in Sheffield (through Sheffield Teaching Hospitals NHS Foundation Trust) and applied this system to one year, 2004. Further analysis by note review will help confirm aetiology and establish the prevalence, incidence, demographics and geographical details.
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