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Background—Iron overload is common in the livers of alcoholics and may play a role in disease pathogenesis. An MHC like gene, HFE,has recently been identified that is mutated in most patients with hereditary haemochromatosis (C282Y in 90% and H63D in 45% of the remainder).Aim—To examine the hypothesis that these mutations determine hepatic iron status in alcoholics and play a role in predisposition to advanced alcoholic liver disease.Methods—TheHFE gene was genotyped in 257 patients with alcoholic liver disease and 117 locally matched healthy volunteers. In addition, iron staining was scored (0–4) on biopsy specimens from fibrotic/cirrhotic patients with and withoutHFE mutations matched for age and sex.Results—Some 15.7% of fibrotic/cirrhotic patients were C282Y heterozygotes compared with 13.7% of controls (p = 0.77). One control and three patients were C282Y homozygotes. Of chromosomes without the C282Y mutation, 68/442 (15.4%) of patients’ chromosomes carried the H63D mutation compared with 36/216 (16.6%) of control chromosomes (p = 0.91). Significant (>grade 1) hepatocyte iron staining was seen in 6/23 C282Y heterozygotes and 4/26 H63D heterozygotes compared with 4/23 controls.Conclusions—Possession of a single copy of either of the two HFEmutations influences neither liver iron content nor the risk of fibrotic disease in alcoholics.

Blood ethanol concentrations after separate oral dosing and intravenous infusion of ethanol (0.15 g/kg) were measured in 16 control subjects and 13 subjects treated with ranitidine. All subjects underwent routine upper gastrointestinal endoscopy. Peak blood ethanol concentrations, and area under the blood ethanol/time curve, were significantly higher in the ranitidine group after oral, but not intravenous, ethanol administration. The first pass metabolism, as calculated by the difference between the area under the curves, was significantly lower in the ranitidine group. In addition, all subjects withdrawn from ranitidine (n = 6) had a significant reduction in peak blood ethanol concentration and area under the curve after repeat dosing with oral ethanol. Both groups were well matched for age, sex, indications for endoscopy, findings at endoscopy, and gastric histology. These findings show that ranitidine increases the bioavailability of low dose ethanol and has possible short term forensic, and longterm physical implications for moderate drinkers who are taking the drug.

Thirty seven patients with established cirrhosis of the liver were subjected to measurement of body protein metabolism using L-(1-14C) labelled leucine as a tracer. The effects of disease severity and those of solutions containing 0%, 16%, 35%, 53%, and 100% branched chain amino acids were evaluated. Significant increases in protein synthesis were noted with solutions containing 35%, 53%, and 100% branched chain amino acids, but in patients receiving 100% branched chain amino acids without additional essential amino acid supplement the increase in synthesis was matched by a significant increase in protein breakdown. Protein balance was thus improved only in patients receiving 35% and 53% branched chain amino acids. It was concluded that the high increase in protein breakdown in patients receiving 100% branched chain amino acids was undesirable, and such a solution should not be recommended for clinical use.

Three patients are described with recurrent jaundice, upper abdominal pain and rigors attributable to dextropropoxyphene hepatotoxicity. The diagnosis was established in each patient by rechallenge; post challenge hepatic histology is reported in two. Twelve previous patients with probable dextropropoxyphene hepatic toxicity have been described and are reviewed. In 10 of the 15 patients, a clinical diagnosis of gall stone disease was made. Liver function tests are usually hepatitic shortly after challenge, but more cholestatic after a few days. No fatalities have been described, but as dextropropoxyphene is widely available in many different analgesic preparations possible toxicity should be considered in patients with relapsing jaundice mimicking biliary disease, in whom gall stones have been excluded.