Hernán Iturriaga

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.

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.

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.

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.

Splanchnic and systemic hemodynamics in early abstinence and after ethanol administration in non-cirrhotic alcoholic patients.

Thirteen asymptomatic chronic alcoholic patients were studied to investigate the early stages of portal hypertension in alcoholic liver disease and the effects of withdrawal and ethanol on hepatic function and hemodynamic variables. None of the patients presented clinical signs of decompensated liver disease, and their liver biopsies showed normal liver or moderate alterations only. In basal conditions and after an intravenous ethanol infusion (1 g/kg body weight), hepatic venous pressure gradient and hepatic blood flow using indocyanine green were measured through hepatic vein catheterization. Hepatic sinusoidal vascular resistance and indocyanine green intrinsic clearance were also calculated. Portal blood flow measurements were obtained by Doppler ultrasound. No correlation was observed between hepatic venous pressure gradient and histologic features, (steatosis, necrosis, fibrosis, inflammation and hepatocyte surface area). In basal conditions, portal hypertension was not found in any case. After ethanol, portal pressure increased significantly (p < 0.001); in four cases it rose to or above 5 mmHg. Portal blood flow, hepatic blood flow and hepatic vascular resistance also increased significantly. Intrinsic indocyanine green clearance decreased slightly but significantly. No significant correlations were found between portal pressure, hepatic resistance and the histologic parameters. It was concluded that alcoholic patients, without clinical or laboratory evidence of liver failure and with minimal or moderate histologic alterations, have normal portal pressures. After an intravenous ethanol load, however, four out of 13 patients (31%) reached levels of 5 mmHg or more, irrespective of their liver histology.

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.

Effects of abstinence on sex hormone profile in alcoholic patients without liver failure

Excessive ethanol ingestion induces hypoandrogenism in male subjects. To confirm its presence and to study its relationship with the degree of liver damage and alcohol abstinence, plasma sex hormones were measured in alcoholic patients without liver failure, after two different abstinence periods. Patients were 30 male chronic alcoholics admitted to the Alcoholism Ward for treatment of their addiction. On admission, we measured: testosterone (T), estradiol (E), follicle stimulating hormone (FSH), luteinizing hormone (LH) and sex-hormone binding globulin (SHBG). A liver biopsy was also performed. These measurements were repeated at discharge and were also done in 15 normal volunteers. On admission (mean abstinence 1.9 ± 1.7 days) total T was similar to controls, FSH was lower (p< 0.02) and high levels of SHBG were found (3.5 fold increase, as compared to controls). Histologically, 9 patients had normal liver; 14 had moderate alterations and 7 showed marked alterations. Hormonal values were not different in these 3 groups. At discharge, 11.1 ± 4.7 days after admission, T, E and FSH did not show significant changes but LH decreased (8.2 ± 5.2 mlU/ml vs 12.9 ± 4.1, p< 0.001); SHBG also decreased (65.4 ± 21.6 nmol/l vs 117.2 ± 33.3, p< 0.001) to values that still were twice those of controls. It is concluded that alcoholic patients withoutclinical signs of liver failure have normal plasma testosterone levels, irrespective of their histologic liver alterations and high plasma SHBG levels that decreased significantly after a short abstinence. The concomitant LH decrease suggests that hypoandrogenism is likely in these patients. Fast changes in SHBG levels rise the possibility that this protein is candidate marker of alcoholism.

Protein turnover in abstinent and non-abstinent patients with alcoholic cirrhosis.

OBJECTIVE This study was designed to measure the effect of chronic alcohol intake on leucine turnover in outpatients with stable alcoholic liver cirrhosis. METHODS Protein turnover rate was measured using L [1-14C] leucine in ten outpatients with proven alcoholic cirrhosis and in five healthy controls. After the performance of the turnover, the patients were divided in two groups depending on the evidence of alcohol ingestion in the previous month. RESULTS Non-abstinent patients had a significantly higher leucine flux and non-oxidative disposal (73.8 +/- 25.4 and 65.9 +/- 21.6) than abstinent cirrhotic patients (48.9 +/- 9.5 and 43.7 +/- 9.0) and normal controls 37.3 +/- 8.9 and 31.1 +/- 7.6 mumol/m2/min (p < 0.01). Leucine oxidation and serum leucine levels were similar in the three groups. CONCLUSION Alcohol intake in alcoholic cirrhotic patients has a catabolic effect that could be associated with the nutritional imbalances observed in alcoholic liver disease.

Increased Blood Ethanol Elimination in Rats Treated with Halothane

The effect of chronic halothane inhalation and blood ethanol elimination was studied in the rat. Hepatic α-glycerophosphate, oxidase ADH and malic enzyme activities were determined. Malic enzyme activity was also assayed in adipose tissue. Halothane-treated rats showed an increased ethanol elimination (378 ± 13 vs. 292 ± 19; p