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Background/aims: In patients with cirrhosis pharmacological treatment of portal hypertension using beta-blockers and vasodilators has raised concerns for its potential deleterious effects on renal function and encephalopathy. To clarify this issue we evaluated the effects of propranolol and 5-isosorbide mononitrate or both on subclinical hepatic encephalopathy and renal function in a prospective randomized double-blinded study., Methodology: Thirty patients Child-Pugh A or B, with esophageal varices, normal renal function and non-previous pharmacological treatment were studied. After a basal period, patients received during 4 weeks 5-isosorbide mononitrate (80 mg/day) or placebo. In the next 4 weeks, propranolol was added to both groups. At baseline and at the end of each study period we assessed: renal function tests; plasma renin activity and aldosterone; subclinical hepatic encephalopathy (electroencephalograms, visual evoked potentials and psychometric studies). Mean arterial pressure, cardiac output (echo-Doppler) and indocyanine green retention were also measured., Results: The most common alterations at baseline were increased arterial ammonia levels (85%), abnormal indocyanine green retention (75%), abnormal trail making B (44%), decreased inulin clearance (30%) and high plasma renin activity (27%). After 4 weeks of 5-isosorbide mononitrate or placebo no significant changes were observed in any variable. Five out of 14 patients receiving 5-isosorbide mononitrate were withdrawn due to side effects. The addition of propranolol decreased significantly plasma renin activity in both groups and cardiac output in those receiving 5-isosorbide mononitrate but did not change other variables., Conclusions: In patients with compensated or slightly decompensated liver cirrhosis 5-isosorbide mononitrate, propranolol or the association of both did not produce detectable worsening of subclinical hepatic encephalopathy or renal function.

Looking for a noninvasive method to predict liver histologic alterations in alcoholic patients without clinical signs of liver failure, we studied 187 chronic alcoholics recently abstinent, divided in 2 series. In the model series (n = 94) several clinical variables and results of common laboratory tests were confronted to the findings of liver biopsies. These were classified in 3 groups: 1. Normal liver; 2. Moderate alterations; 3. Marked alterations, including alcoholic hepatitis and cirrhosis. Multivariate methods used were logistic regression analysis and a classification and regression tree (CART). Both methods entered gamma-glutamyltransferase (GGT), aspartate-aminotransferase (AST), weight and age as significant and independent variables. Univariate analysis with GGT and AST at different cutoffs were also performed. To predict the presence of any kind of damage (Groups 2 and 3), CART and AST > 30 IU showed the higher sensitivity, specificity and correct prediction, both in the model and validation series. For prediction of marked liver damage, a score based on logistic regression and GGT > 110 IU had the higher efficiencies. It is concluded that GGT and AST are good markers of alcoholic liver damage and that, using sample cutoffs, histologic diagnosis can be correctly predicted in 80% of recently abstinent asymptomatic alcoholics.

The relationship between the content of hepatic reduced glutathione (GSH) and the length of abstinence was investigated in 45 chronic alcoholic patients. Hepatic GSH levels were significantly correlated (r = 0.58; P less than 0.001) with the length of alcohol withdrawal in the whole group. According to liver histology patients were divided into two groups, with and without hepatic necrosis. Subjects without necrosis showed a significant positive correlation (r = 0.71; P less than 0.001) between GSH values and the length of abstinence; no correlation (r = -0.22; P less than 0.40) was observed in the group with necrosis. According to the period of abstinence patients were separated into two groups, with a short (less than or equal to 5 days) and a prolonged (greater than 5 days) alcohol withdrawal. Patients with and without necrosis exhibited comparable mean levels of liver GSH (2.04 +/- SEM 0.21 and 1.74 +/- 0.23 mumol/g respectively; P less than 0.30) when studied after short periods of abstinence. Alcoholics without liver necrosis showed significantly higher hepatic GSH levels than those with necrosis (3.23 +/- 0.30 and 1.60 +/- 0.33 respectively; P less than 0.01) after prolonged periods of alcohol withdrawal. Similar results were obtained when liver GSH levels were expressed as a function of the mean surface area of hepatocytes, which was not significantly different between patients with and without hepatic necrosis. Parameters assessing the nutritional status of patients with and without necrosis were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

This study analyzes whether increased body weight is related to histological liver damage in chronic alcoholic patients. Data from 152 recently abstinent alcoholics without evidences of liver failure were analyzed. Liver biopsies were scored for the presence of fat, necrosis, fibrosis, inflammation, and Mallory material. Total histological score correlated significantly with body weight (BW), length of alcoholism (L), and age (A) but not with the amount of ethanol ingested (E). Forward stepwise multiple regression analysis with histological score as the dependent variable gave significant F values for BW and L but not for A. Patients with severe damage had higher BW than patients with mild damage. The group with BW greater than 110% showed a higher histological score. These results confirm the association between increased BW and liver damage in asymptomatic alcoholic patients suggesting that overweight is a risk factor for alcoholic liver disease.

To determine whether hepatic hypoxia is associated with hepatocellular necrosis in alcoholics, oxygen tension in the hepatic vein and hepatic blood flow were determined in thirteen patients without overt clinical liver disease. Ethanol metabolic rate was also assayed as an index of liver metabolism. Hepatic blood flow and ethanol metabolic rate were also determined in six normal volunteers. According to liver histology patients were separated into two groups, with and without hepatocellular necrosis. Alcoholics with necrosis showed a higher (P less than 0.002) ethanol metabolic rate (4.05 +/- 0.23 mmol/kg/h) than those without necrosis (2.46 +/- 0.34). Hepatic blood flow in the total group of alcoholics was not significantly different from controls; in the group with necrosis it was lower (651.7 +/- 44.6 ml/min/m2) than in the group without necrosis (878.3 +/- 81.6; P less than 0.025). Hepatic vein pO2 was lower (P less than 0.01) in patients with hepatocellular necrosis (31.7 +/- 0.68 mmHg) than in patients without necrosis (35.7 +/- 0.99). In the whole group, a significant negative correlation (r = 0.76, P less than 0.003) was observed between hepatic vein pO2 and ethanol metabolic rate. Acute administration of ethanol (21.7 mmol/kg) did not alter hepatic blood flow in six normal individuals nor in five alcoholic patients, although an increase in hepatic vein pO2 was observed in the latter. The changes observed in hepatic vein pO2 functional hepatic blood flow, and ethanol metabolic rate which correlate with hepatocellular necrosis, may be of pathogenic importance in alcoholic liver disease.