G. Ugarte

Controlled Trial on Nutrition Supplementation in Outpatients With Symptomatic Alcoholic Cirrhosis

A controlled trial on nutrition supplementation in ambulatory patients with decompensated alcoholic liver disease was carried out during 1 year. Fifty-one patients were studied; 26 were assigned to an experimental group receiving a daily supplement of 1000 kcal and 34 g of proteins given as a casein-based enteral nutrition product and 25 to a control group receiving one placebo capsule. Patients were examined in a special clinic once a month or more if required. Sixty-eight percent of patients admitted to alcohol ingestion or had alcohol in urine samples on at least one occasion. Dietary recalls showed a significantly higher protein and caloric intake in case patients subjects (p < .0001). Nine patients died during the study, three case patients and six control patients (p = NS). The frequency of hospitalizations was significantly less in the experimental group. This difference was attributed to a reduction in severe infections. Mid-arm circumference, serum albumin concentration, and hand grip strength improved earlier in case patients, although both groups had a significant improvement in these parameters. Bilirubin and aspartate aminotransferase decreased and prothrombin time increased significantly in both groups during the study period, without differences between groups. It is concluded that nutrition support decreases nutrition-associated complications in patients with alcoholic liver disease.

Effect of acute ethanol intoxication on the content of reduced glutathione of the liver in relation to its lipoperoxidative capacity in the rat

Glutathione is considered to be the most abundant and important intracellular sulfhydryl compound [ 1.21. Both reduced (GSH) and oxidized (GSSG) glutathione are related to several structural and func- tional processes of the cell, and are involved in the protective mechanisms against the deleterious effects of several agents and/or their metabolites [2]. The later function of glutathione has been proposed to be accomplished by either the formation of excretable conjugates [3] or by its participation in the metabolism of peroxides arising from the enhancement of lipo- peroxidative processes [4]. Lipoperoxidation, the oxidative alteration of poly- unsaturated fatty acids that seems to be of importance in the production of liver injury by some hepato- toxins [5,6], has been shown to be increased in the liver following acute [7-l 0] and chronic [8,1 l-141 alcohol ingestion. However, this finding has not been confirmed in the acute model [ 15 171. This report describes the influences of the sex, nutritional status, dosage and the period of intoxication of animals given alcohol acutely on the content of GSH of the liver in relation to its lipoperoxidative capacity. The effect of alcohol on the activity of the enzymes of peroxide metabolism, the other main contributors to the maintenance of the antioxygenic capacity of the hepatocyte [1,4,18], is dealt with in [19]. 2.

Hepatic vein oxygenation, liver blood flow, and the rate of ethanol metabolism in recently abstinent alcoholic patients

Abstract. 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 < 0–002) ethanol metabolic rate (405±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 < 0025). Hepatic vein pO2 was lower (P < 001) 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 < 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.

Effect of acute ethanol ingestion on lipoperoxidation and on the activity of the enzymes related to peroxide metabolism in rat liver.

Data presented in [l] show that acute ethanol administration to rats stimulates hepatic lipoperoxida. tive processes in conditions of maximal depletion of the content of reduced glutathione (GSH). Apart from the content of tissue GSH, the levels of vitamin E as well as the activity of the enzymes related to peroxide metabolism have been suggested to contribute to the maintenance of the antioxygenic capacity of the liver cell [2-41. This work deals with the influence of acute ethanol ingestion on liver lipoperoxidation in relation to the activity of: (i) Superoxide dismutase and catalase as an antioxidant system preventing lipoperoxide formation by free radicals; (ii) Glutathione (GSH)-peroxidase and glutathione (GSSG)-reductase as a detoxifying system decomposing hydroperoxides and hydrogen peroxide (H,Oz) to inactive metabolites [4].

Effect of (+)-Cyanidanol-3 on the Changes in Liver Glutathione Content and Lipoperoxidation Induced by Acute Ethanol Administration in the Rat

Acute ethanol administration to rats fasted overnight resulted in a significant decrease in the content of glutathione (GSH) of the liver concomitantly with a partial increase in oxidized glutathione levels, representing a net 38% decrease in total GSH equivalents. In these conditions, liver lipoperoxidation is significantly enhanced. Treatment with (+)-cyanidanol-3 prior to ethanol ingestion was able to reduce by 80% the ethanol-induced depletion in total GSH equivalents and to completely abolish lipoperoxidation. These results indicate that (+)-cyanidanol-3 has a protective effect on the changes in liver GSH levels and lipoperoxidation induced by ethanol, probably related to its scavenging action exerted on free radicals.

Nitrogen economy in alcoholic patients without liver disease

Nitrogen balance was studied in five alcoholic patients during alcohol consumption and after 1 or 2 weeks of abstinence, under metabolic ward conditions. Patients had a history of excessive ethanol intake for five years or more. They were intoxicated and otherwise asymptomatic on admission and had been drinking 150 g or more of ethanol daily, for at least one month. Subjects consumed a diet providing vitamins and minerals exceeding RDA values, 45 kcal/kg of body weight and 0.6 g/kg of proteins (as egg protein), for 33 days. During the first 11 days patients received 200 g of ethanol that were isocalorically substituted later by dietary fat and carbohydrates. The results of this study show that, in alcoholic patients while drinking and after seven days of alcohol withdrawal, nitrogen balance is significantly decreased compared to that performed after two weeks of abstinence. Ethanol metabolic rate was found to be increased, compared to controls. It was lower in four of five patients after the second week of abstinence. These results suggest that alcohol abuse increases protein requirements in chronic alcoholic patients even without histologic liver disease or clinical signs of gastroenterologic disorders.

Hepatic alcohol dehydrogenase in alcoholic addicts with and without hepatic damage

SummaryHepatic alcohol dehydrogenase was measured in liver homogenates from normal, moderate drinkers, and from alcoholics with normal livers, steatosis, and liver cirrhosis.Hepatic alcohol-dehydrogenase activity was 0.37±0.12 µM/hr./mg. of protein in the normals, 0.18±0.13 µM/hr/mg. in alcoholics with normal liver histology, 0.12±0.09 µM/hr./mg. in alcoholics with fatty liver, and 0.12±0.08 µM/hr./mg. in patients with alcoholic cirrhosis. Alcohol dehydrogenase was significantly lower among alcoholics. There was no difference in the activity of this enzyme between alcoholic patients with liver damage and those without liver damage.

Possible relationship between the rate of ethanol metabolism and the severity of hepatic damage in chronic alcoholics

The rate of ethanol metabolism (EMR) was determined in alcoholic patients with or without hepatic necrosis, steatosis, and/or cirrhosis. Fifty six cases were studied after 9–25 days of abstinence (mean 15 days). A significant increase in EMR (P<0.01) was found in alcoholics with hepatic necrosis (265±20.5 mg/kg/hr) compared with alcoholics with normal liver histology (154±17) and nonalcoholic controls (159±15). In alcoholics with liver steatosis but without necrosis a lesser increase in EMR (207±20,P<0.05) was also observed. Patients with slight fibrosis but without other abnormalities in their liver biopsies and cirrhotics with overt liver failure (jaundice, ascites) showed EMR similar to controls.

Glucose tolerance and the insulin response in recently drinking alcoholic patients: possible effects of withdrawal.

To investigate possible effects of withdrawal on carbohydrate metabolism in chronic alcoholic patients, intravenous glucose tolerance tests were performed in three periods in 11 alcoholic patients: early abstinence (less than three days), early abstinence plus ethanol (1 g/kg/BW IV), and late abstinence (three weeks later). According to liver biopsy results and laboratory tests, patients were classified as a group with liver damage (four cases) and a group without it (seven cases). In the group without damage, glucose tolerance expressed as K% and compared to a control group, was significantly decreased in early and late abstinence but not after the infusion of ethanol. Cases with damage also had glucose intolerance at admission. Plasma insulin levels after the glucose load were significantly lower at ten and 30 minutes in the group without damage, in early or late abstinence. They were normal in the presence of ethanol. Patients with liver damage presented higher basal and postglucose plasma insulin concentrations. It was concluded that glucose intolerance in alcoholic patients is a common finding that occurs in the presence or absence of liver damage. In cases with liver damage it seems to be due to peripheral insulin resistance. In those without damage it is related to low peripherovenous insulin levels.

Glucose Turnover Rate and Peripheral Insulin Sensitivity in Alcoholic Patients without Liver Damage

Glucose intolerance is frequently found in alcoholic patients and an impaired insulin response has been documented in them. To look for alternative mechanisms that could explain this intolerance, a glucose turnover using tritiated glucose and an euglycemic glucose clamp were performed to measure the glucose production rate and peripheral insulin sensitivity, respectively. Two groups of recently abstinent chronic male alcoholic patients without evidence of liver damage were studied. The glucose turnover technique showed a higher basal glucose production rate in alcoholics, compared with normal volunteers (2.83 +/- 0.29 vs. 1.84 +/- 0.22 mg/kg/min); an intravenous ethanol load significantly increased this rate. The euglycemic glucose clamp did not show peripheral insulin resistance in alcoholics, compared with controls.