Background-The Dionysos Study is a cohort study of the prevalence of chronic liver disease in the general population of two northern Italian communities. It included 6917 subjects, aged 12-65 (69% of the total population). Aims-The aim of this part of the study was to examine the relationship of daily alcohol intake, type of alcoholic beverage consumed, and drinking patterns to the presence of alcohol induced liver damage in an open population. Patients and methods-6534 subjects, free of virus related chronic liver disease and participating in the first cross-sectional part of the study, were fully examined. Each subject underwent: (a) medical history and physical examination, (b) evaluation of alcohol intake using an illustrated dietary questionnaire, and (c) routine blood tests. More invasive diagnostic procedures were performed when indicated. Results-Multivariate analysis showed that the risk threshold for developing either cirrhosis or non-cirrhotic liver damage (NCLD) was ingestion of more than 30 g alcohol per day in both sexes. Using this definition, 1349 individuals (21% of the population studied) were at risk. Of these, only 74 (5.5% of the individuals at risk) showed signs of liver damage. The prevalence of "pure" alcoholic cirrhosis was 0.43% (30 of 6917), representing 2.2% of the individuals at risk, with a ratio of men to women of 9:1, while 44 (3.3% of the individuals at risk) showed persistent signs of NCLD. After 50 years of age, the cumulative risk of developing both NCLD and cirrhosis was significantly higher (p<0.0001) for those individuals who regularly drank alcohol both with and without food than for those who drank only at mealtimes. Conclusions-Our data show that in an open population the risk threshold for developing cirrhosis and NCLD is 30 g ethanol/day, and this risk increases with increasing daily intake. Drinking alcohol outside mealtimes and drinking multiple diVerent alcoholic beverages both increase the risk of developing alcohol induced liver damage. (Gut 1997; 41: 845-850)

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Clinical course in hepatocellular carcinoma may be very different. We prospectively evaluated 96 patients with hepatocellular carcinoma unsuitable for radical therapy to investigate factors that could influence survival. Clinical, pathologic, and molecular data of patients were analyzed by univariate and multivariate analysis. The overall actuarial probability of survival at year 1, 2, 3, 4, 5, and 6 was 72%, 41%, 38%, 24%, 20%, and 9%. At univariate analysis, alphafetoprotein (AFP) (P ‫؍‬ .0082); alkaline phosphatase (P ‫؍‬ .0281); bilirubin (P ‫؍‬ .0076); etiology (P ‫؍‬ .0001); increment of tumor mass at month 3 (P ‫؍‬ .0051); type of estrogen receptor (ER) in the tumor (P ‫؍‬ .0000); prothrombin time (P ‫؍‬ .0003); and portal vein thrombosis (P ‫؍‬ .0000) had prognostic significance. At multivariate analysis, only type of ER (P ‫؍‬ .0000) and bilirubin (P ‫؍‬ .0030) showed independent predictive value for mortality. Survival was significantly longer in patients with wild-type estrogen receptors (P ‫؍‬ .0000). Cumulative probability of survival at year 1, 2, 3, 4, 5, and 6 was 94%, 66%, 52%, 43%, 35%, and 18% for wild-type and 51%, 21%, 16%, and 9% for variant estrogen receptors (no patients alive after 4 years). Hepatitis B surface antigen ( Survival of patients with hepatocellular carcinoma (HCC) as reported in different series of patients is extremely variable, ranging from a few months to several years. 1-6 Different studies, especially from Japan, have shown that differences in survival may be related not only to the size of the tumor or the presence of extrahepatic metastasis 5 but also to the stage of the underlying cirrhotic disease, survival being much shorter in patients with decreased serum albumin and increased bilirubin. 1 A relevant characteristic of a subgroup of these tumors, which has been underlined but not explained by different investigators, 2,3 is a remarkable difference in growth speed, which determines significantly different doubling times 2 ; furthermore, a sudden increase in tumor growth rate has been described in some tumors, even in those that were very small at presentation. 2 A similar behavior has also been evidenced in a western epidemiologic setting in a series of untreated patients with HCC 3 : in some patients tumors had a very short doubling time (Ͻ150 days) and in others doubling time was much longer (Ͼ300 days). Using a score based on albumin, alcohol intake, number of nodules, echo pattern, and histologic type, the investigators were able to predict which patients would be characterized by long doubling time 4 ; also remarkable was the lack of significant correlation between initial size of the tumor and subsequent doubling times. 4 A practical consequence of this highly variable behavior is that, despite implementation of screening programs, not more than 20% to 40% of HCCs are detected at curable stage. 7 We have previously shown that HCC, especially in men, is characterized by an exon 5-deleted estrogen receptor transcript, which gives rise to an estrogen receptor al...

Summary Variant liver oestrogen receptor transcripts in hepatocellular carcinoma are associated with aggressive clinical course and unresponsiveness to tamoxifen. To evaluate the impact on survival and on tumour growth of megestrol (progestin drug acting at postreceptorial level) we enrolled 45 patients with HCC characterized by variant liver oestrogen receptors in a prospective, randomized study with megestrol vs. placebo. Presence of variant oestrogen receptors was determined by RT/PCR. 24 patients were randomized to no treatment and 21 to therapy with megestrol 160 mg day -1 . Results were analysed by Kaplan-Meier and Cox methods. Survival of hepatocellular carcinoma characterized by variant oestrogen receptors was extremely poor (median survival 7 months); megestrol significantly improved survival (18 months) (P = 0.0090). Tumour growth at one year was significantly slowed down in megestrol-treated patients (P = 0.0212). Bilirubin levels, presence of portal thrombosis, HBV aetiology and treatment were identified at univariate analysis as factors significantly associated with survival; at multivariate analysis, only megestrol therapy (P = 0.0003), presence of HBV infection (P = 0.0009) and presence of portal vein thrombosis (P = 0.0051) were factors independently related with survival. (1) Megestrol slows down the aggressive tumour growth of patients with hepatocellular carcinoma characterized by variant estrogen receptors and (2) is also able to favourably influence the course of disease, more than doubling median survival.

Age, ingestion of a strong acid, leucocytosis, deep gastric ulcers, and gastric necrosis are predictive of death after caustic ingestion. A risk score system including these predictors may be useful in prognostic evaluation.