bility to ALD have thus far focused primarily on genes encod-SEE EDITORIAL ON PAGE 232 ing ethanol metabolizing enzymes. 3 Results have been conflicting, but it would appear that the known polymorphisms of genes encoding the alcohol and aldehyde dehydroTwin concordance studies suggest that genetic factors play genase enymes and the ethanol-inducible cytochrome P450, a role in determining why only a minority of heavy drinkers CYP2E1, play only a minor role in the Caucasian populadevelop hepatitis and cirrhosis. Tumor necrosis factor a tion. [5][6][7] These results have led to a search for alternative ''can-(TNF-a) has emerged as the ''final common pathway'' in the didate genes'' potentially involved in determining individual pathogenesis of alcohol-related hepatic necro-inflammation.susceptibility to advanced ALD. We have examined the frequency of the two recently de-The cytokine tumor necrosis factor a (TNF-a) has recently scribed polymorphisms of the TNF-a promoter in 150 paemerged as an important mediator of hepatic necro-inflamtients with biopsy-proven alcoholic liver disease and 145 mation associated with excessive alcohol intake. 8 Investigahealthy volunteers. There was a significant excess of the rare tion of the role of TNF-a and other cytokines in alcoholic allele (TNFA-A; G 0238 r A) at position 0238 in patients with steatohepatitis was first stimulated by the striking similarity steatohepatitis compared with controls or patients without observed between the metabolic complications of ASH and this lesion. This is consistent with previous suggestions that the metabolic effects of cytokines, including TNF-a. 8 Inthe TNFA-A allele, which falls within a putative Y regulation creased TNF-a production by peripheral blood monocytes box of the TNF-a promoter, is associated with increased TNFand Kupffer cells has been shown in patients with ASH and a expression. No differences were observed for the polymoranimal models of alcoholic liver injury. 9,10 Several investigaphism at position 0308. (HEPATOLOGY 1997;26:143-146.)tors have shown increased plasma levels of TNF-a activity in patients with ASH 11-15 and some have shown a correlation In common with other end-organ complications of alcohol with liver function and mortality. 11,14 TNF-a is cytotoxic to abuse, severe liver disease develops in only a minority of sensitized hepatocytes and has been implicated as a proximal heavy drinkers. In several biopsy studies alcoholic steatohepmediator in experimental liver injury induced by Propionibacatitis (ASH), characterized by steatosis and necroinflammaterium acnes, galactosamine, lead and endotoxin, and ischtion, is present in 6% to 30% of heavy drinkers, with estabemia-reperfusion. 8 In humans, reversible hepatitis is one of lished cirrhosis in less than 20%. 1 Although some evidence the toxicities of human recombinant TNF-a administered for supports a dose-response relationship between alcohol contherapy to cancer patients. 16 sumption and risk of disease, 2 it is clear that factors other Recently, two polymorphi...

in the IL-10 promoter is associated with an increased risk of advanced liver disease. This is consistent with recent functional data that the −627*A allele is associated with low IL-10 expression which will favour inflammatory, immune mediated, and profibrotic mechanisms of alcohol related liver injury. (Gut 2000;46:540-545)

In this study we have determined the incidence of hePrimary biliary cirrhosis (PBC) is a chronic cholestatic liver disease with an autoimmune etiology. 1 The disease is patocellular carcinoma (HCC) development in primary biliary cirrhosis (PBC) and its effects on patient survival. progressive, and a significant proportion of patients eventually develop cirrhosis. The presence of cirrhosis, regardless Six hundred and sixty seven patients with liver histology compatible with or diagnostic of PBC were seen over a of its etiology, is a major risk factor for the development of hepatocellular carcinoma (HCC). 2 Studies that have exam-20-year period. Two hundred and seventy three patients who had stage III or IV disease on their last biopsy and ined factors underlying the development of HCC have, however, suggested that cirrhotic PBC is a relatively rare precurwho had been followed up for at least 1 year following that biopsy (total follow-up with advanced disease 2,010 sor to HCC development, [3][4][5] even in the Northern European population in which the incidence of PBC appears to be patient years) were identified (243 female, 30 male). Patients who developed HCC were identified and their con-particularly high. 6 Although they suggest that HCC developing in end-stage PBC contributes relatively little to the founding risk factors were excluded. Mayo risk scores were calculated for each clinic attendance and expected overall incidence of HCC, such studies do not allow us to ascertain the actual risk of HCC development for individual survival for each time point was compared with subsequent actual survival. Sixteen cases of HCC were seen in groups of PBC patients. Published reports of HCC in PBC have, to date, been restricted to limited case series, 7-10 thereby the patients with stage III or IV disease on last biopsy, providing an overall incidence of 5.9% in this group. preventing us from estimating the true incidence of HCC development in PBC and from assessing the impact that priFourteen of these patients had died of HCC related causes, and 2 patients were alive at the census point. The mary liver cancer development has on patient survival. The aims of the present study were as follows: to determine the incidence of HCC was significantly higher in males with stage III/IV disease than in females (20% vs. 4.1%, P õ incidence of HCC development in a large population-based cohort of PBC patients followed-up over a 20-year period; to .005). Nine of one hundred and eight (8.3%) total female deaths in this group was attributable to HCC compared determine which subgroups of PBC patients were at the highest risk of HCC development; to study the impact that HCC with 5 of 11 (45.5%, P õ .05) male deaths. HCC was not seen in any of the 394 patients with stage I and II PBC development had on disease prognosis; and to study the extent to which adverse outcome was anticipated by the most followed-up over the same time period. Throughout the disease course of all PBC patients with HCC, the Mayo widely accepted predictor of disease...

Background-Few studies have compared vasoactive drugs with endoscopic sclerotherapy in the control of acute variceal haemorrhage. Octreotide is widely used for this purpose, but its value remains undetermined. Aims-To compare octreotide with endoscopic sclerotherapy for acute variceal haemorrhage. Patients-Consecutive patients with acute variceal haemorrhage. Methods-Patients were randomised at endoscopy to receive either a 48 hour intravenous infusion of 50 µg/h octreotide (n=73), or emergency sclerotherapy (n=77).Results-Overall control of bleeding and mortality was not significantly diVerent between octreotide (85%, 62 patients) and sclerotherapy (82%, 63 patients) over the 48 hour trial period (relative risk of rebleeding 0.83; 95% confidence interval (CI) 0.38 to 1.82), irrespective of Child's grading or active bleeding at endoscopy. One major complication was observed in the sclerotherapy group (aspiration) and two in the octreotide group (pulmonary oedema, severe paralytic ileus). During 60 days of follow up there was an overall trend towards an increased mortality in the octreotide group which was not statistically significant (relative risk of dying at 60 days 1.91, 95% CI 0.97 to 3.78, p=0.06). Conclusions-The results of this study indicate that intravenous octreotide is as eVective as injection sclerotherapy in the control of acute variceal bleeding, but further controlled trials are necessary to evaluate the safety of this treatment. (Gut 1997; 41: 526-533)