Severity of alcohol dependence in decompensated alcoholic liver disease: comparison with heavy drinkers without liver disease and relationship to family drinking history.

AIM: The aim of this study was to compare alcohol dependence severity in patients with severe alcoholic liver disease (ALD) with that in heavy drinkers without liver disease. METHODS: Short alcohol dependence data and lifetime alcohol questionnaires applied to unselected heavy alcohol drinkers (>60 units/week (M) or 40 units/week (F) for >5 years) with either (a) decompensated ALD (patients n = 136) or (b) no evidence of serious liver disease by clinical, biochemical and ultrasound evaluation ('controls' n = 148). RESULTS: The SADD alcohol dependence severity score (range 0-42) in patients with ALD was >28 (severe dependence) in 36 cases (26%); slightly higher than that in heavy-drinking controls taken as a whole; similar to that in controls who were seeking healthcare but higher than that in controls who were not; and lower than that in controls who attended specialist alcohol services. In ALD patients and controls, the SADD score was higher in those with three or more heavy-drinking first-degree relatives than in those with none. In multiple regression analysis, the SADD score showed independent associations with young age, clinically manifest alcohol dependence, seeking healthcare and the presence of multiple heavy drinking relatives, but not with ALD. CONCLUSIONS: Alcohol dependence severity in patients with ALD varies and tends to be lower than that in heavy drinkers seeking treatment at alcohol treatment centres but is not as low as implied in some previous studies. Alcohol dependence severity is associated with young age and family drinking history but is not specifically associated with the development of liver disease.

Cytokine gene polymorphisms in heavy drinkers with and without decompensated liver disease: a case-control study.

BACKGROUND: Twin studies have suggested some genetic predisposition to alcoholic liver disease (ALD). Cytokines may be involved in ALD pathogenesis. Several cytokine genes contain functionally significant polymorphisms. Associations between ALD and polymorphisms on the interleukin-1 (IL-1), IL-10, and tumor necrosis factor-alpha (TNF-alpha) genes have been reported but not confirmed. OBJECTIVE: Comparison of allelic frequencies of cytokine gene polymorphisms between 223 patients with decompensated ALD (a more severe phenotype than in previous studies) and 162 controls with similar lifetime alcohol consumption but without serious liver disease. METHODS: Genotyping of polymorphisms of the genes for IL-1A (+4,845), IL-1B (+3,954 and -511), IL-1 receptor antagonist (+2,018), IL-6 (-174), IL-10 (-574 and -1,117), and TNF-alpha (-238 and -308). RESULTS: There were increases with respect to IL-6 -174 (2 x 3 chi(2)P < 0.1, OR for G allele carriage 1.61[1.05-2.48]) and Il-10 -592 (2 x 3 chi(2) 7.90, P < 0.01, OR for AA genotype carriage 4.85[1.40-16.8]) polymorphisms in patients compared with heavy-drinking controls. Differences were greater with analysis confined to Child's C patients. Genotype distribution for the other seven polymorphisms did not differ significantly between patients and heavy-drinking controls. CONCLUSION: These data are consistent with a modest role for IL-6 -174, and IL-10 -592 polymorphisms in genetic susceptibility to ALD.

Familial predisposition to alcoholic liver disease: a case-control study.

OBJECTIVES: The variable susceptibility to alcoholic liver disease (ALD) may be genetic in origin, but clear candidate genes have not yet emerged. This study aimed to assess familial clustering of ALD using a case-control strategy. METHODS: We recruited two cohorts of heavy drinkers (>60 U/week for men or >40 U/week for women): 291 individuals with decompensated ALD (Child's grade B or C) and 208 controls with similar alcohol consumption but no evidence of liver disease. Data were collected, through a questionnaire and a follow-up telephone call, on drinking behaviour and the presence of liver disease in parents and siblings of cases and controls. The results in the relatives of cases were compared with those in the relatives of the controls. RESULTS: The odds ratio (OR) of heavy drinking in the relatives of the cases compared with the controls was 0.91 [95% confidence interval (CI), 0.73-1.1]. OR in the relatives of the cases versus the controls was 1.27 for definite ALD (95% CI, 0.63-2.6), 1.09 for all ALD (95% CI, 0.58-2.0) and 1.0 for all liver diseases (95% CI, 0.60-1.7). Multiple subgroup analyses yielded similar OR values, not exceeding 1.5. CONCLUSION: These data do not suggest a strong familial predisposition to the development of ALD and rather suggest that the main cofactors are environmental.

Bouveret's Syndrome: a Case Report.

Bouveret's syndrome is a well known clinical entity; its incidence however, is uncommon. An unusual complication of cholelithiasis, Bouveret's syndrome should be considered in an elderly patient presenting with acute gastric outlet obstruction.We describe a case of an elderly female patient presenting with acute gastric outlet obstruction secondary to a massive gallstone and discuss the imaging appearances and therapeutic options for this rare condition.

HFE genotypes in decompensated alcoholic liver disease: phenotypic expression and comparison with heavy drinking and with normal controls.

OBJECTIVES: Predisposition to alcoholic liver disease (ALD) may be partly genetic. Heterozygosity for the HFE mutations C282Y and/or H63D has been associated with more severe disease in several liver conditions. Studies in ALD have not used controls matched for alcohol consumption and results have been conflicting. METHODS: HFE genotyping was performed in two Caucasian heavy-drinking cohorts (>60 units/wk (M) or 40 units/wk (F) for >5 yr): (a) 254 patients with decompensated ALD (Child's grade B or C), (b) 130 controls with similar alcohol consumption but without liver disease. Results in males were also compared with those from another study of healthy male blood donors. RESULTS: (1) Genotype distributions for the C282Y and H63D mutations were similar in ALD patients, heavy-drinking controls, and healthy blood donors. (2) ALD patients with and without HFE mutations had similar disease severity, age at presentation, and alcohol consumption. (3) Increased serum ferritin and % transferrin saturation were seen in 63% and 29% of ALD patients, regardless of HFE genotype; the increased % transferrin saturation was due to reduced unsaturated iron binding capacity, rather than increased serum iron. (4) Stainable liver iron was present in 52% of patients; grade was greater in patients with two HFE mutations than in those with one or with none. (5) Only the two C282Y homozygote patients had substantial iron overload. CONCLUSIONS: Although serum iron abnormalities are common, C282Y and H63D mutation frequencies were not increased in heavy drinkers with decompensated liver disease. HFE mutations, although modestly influencing liver iron, do not predispose to clinically significant ALD.