Effects of alcohol and liver cirrhosis on the GH-IGF-I axis

Decreased serum insulin-like growth factor (IGF-I) levels have been shown in malnutrition and liver diseases. To analyse which of them is the main cause of GH-IGF-I axis alterations, serum levels of growth hormone (GH), growth-hormone releasing factor (GHRH), IGF-I and its binding protein IGFBP-3 were measured in 85 hospitalized alcoholics (51 without cirrhosis, 15 with compensated cirrhosis and 19 with cirrhosis with ascites) and in 25 healthy controls. Liver function tests and objective nutritional assessment were also performed. Serum IGF-I and IGFBP-3 levels were lower in alcoholics, particularly in those with liver cirrhosis. Serum GH was raised in cirrhotics with ascites but GHRH levels were not significantly altered. Although these patients were frequently malnourished there was no relationship between data derived from GH-IGF-I axis and nutritional parameters. However, there was a significant positive correlation between serum GH concentrations and impaired liver function and a significant negative correlation between serum IGF-I and IGFBP-3 and impaired liver function. This suggests that, in this population, serum IGF-I and IGFBP-3 levels reflect liver dysfunction rather than malnutrition.     

Meta-analysis of the effects of alcohol dehydrogenase genotype on alcohol dependence and alcoholic liver disease

The purpose of this paper is to assemble and evaluate existing data on the effect of genetic variation in ADH2 and ADH3 on the risk of alcohol dependence, and on the risk of alcoholic liver disease. Calculations of odds ratios and their confidence limits, and tests for heterogeneity of the results from the available studies, have been performed. It is clear that possession of the ADH2-2 allele decreases the risk of alcohol dependence, but it increases the risk of alcoholic liver disease among alcoholics. ADH3 variation also has significant effects on alcohol dependence, which may be due to linkage to ADH2; the ADH3 effect differs significantly between Asian and European subjects. Therefore ADH genotype has substantial effects on risk of alcohol dependence and alcoholic liver disease, but more work is needed on the generalizability of these findings to non-Asian populations, and on possible mechanisms.     

Relationships among alcohol availability, drinking location, alcohol consumption, and drinking problems in adolescents

We examined relationships among perceived alcohol availability, drinking location, alcohol consumption, and drinking problems. Subjects were 3,372 adolescent drinkers, ages 16-18, who participated in the Communities Mobilizing for Change on Alcohol Project baseline survey. Mixed-model regression was employed to identify predictors of alcohol consumption and drinking consequences. Perceived alcohol availability was significantly associated with higher levels of alcohol consumption for males. Drinking in a public location with higher levels of alcohol consumption for females. Results underscore the importance of youth alcohol assessibility.     

Gastric clearance of serum albumin in patients with alcoholic liver cirrhosis

Gastric albumin clearance studies were carried out in 26 patients with alcoholic cirrhosis and in 10 control subjects. The mean clearance was significantly higher in patients than in control subjects. An increased protein gastric loss in cirrhotic patients was observed only in presence of gastritis. The presence or absence of distended esophageal varices did not influence the protein loss.     

Distractibility moderates the relation between automatic alcohol motivation and drinking behavior.

Research suggests that alcohol use is influenced by (a) the strength of automatic motivational responses to alcohol cues and (b) individual differences in self-control. The current study was designed to examine whether the self-control skill of inhibiting response to distracting stimuli would moderate the relation between automatic alcohol motivation and alcohol use. Eighty-seven hazardous drinkers completed baseline measures of automatic alcohol motivation and trait self-control and reported their drinking at a follow-up session 6 weeks later. Regression analyses demonstrated an interaction such that greater distractibility strengthens a positive relation between alcohol use and automatic alcohol motivation. These results contribute to a growing body of work indicating that self-control resources may help to inhibit the influence of automatic processes on alcohol behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rehabilitation of patients with alcoholic liver cirrhosis after orthotopic liver transplantation: a 7-year follow-up

Endemic infectious diseases still constitute a threat to Latin American countries. In view of this, research on tropical medicine should be encouraged, particularly in countries like Brazil where this kind of scientific investigation was historically highly early in this century. It is suggested that more resources should be made available to stimulate such studies and the publication in English, Portuguese and Spanish.     

Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial

BACKGROUND/AIMS: Silymarin has protective effects in different experimental conditions, but its efficacy in human liver cirrhosis has not been completely established. Therefore, this study was carried out to determine the effect of silymarin in alcoholics with liver cirrhosis with respect to survival and clinical and laboratory changes. METHODS: From February 1986 to June 1989, we enrolled 200 alcoholics with histologically or laparoscopically proven liver cirrhosis in a randomized, double-blind multicenter trial comparing 450 mg of silymarin (150 mg/ three times per day) with placebo. The primary outcome was time to death, and the secondary outcome was the progression of liver failure. Additional analyses were also performed in 75 patients in whom anti-hepatitis C virus antibodies were measured after completion of the trial. RESULTS: One hundred and three patients were assigned to receive silymarin and 97 to receive placebo. The two groups were well matched for demographic and baseline clinical and laboratory features. A 2-year study period was completed in 125 patients (57 receiving silymarin and 68 receiving placebo). Twenty-nine patients (15 receiving silymarin, and 14 receiving placebo) died during the trial. Survival was similar in patients receiving silymarin or placebo. The effect of silymarin on survival was not influenced by sex, the persistence of alcohol intake, the severity of liver dysfunction or by the presence of alcoholic hepatitis in the liver biopsy. Silymarin did not have any significant effect on the course of the disease. No relevant side-effects were observed in any group. CONCLUSIONS: The results of this study indicate that silymarin has no effect on survival and the clinical course in alcoholics with liver cirrhosis.     

A controlled clinical trial of methylprednisolone in patients with the cholestatic form of alcoholic liver cirrhosis

Fourty patients with alcoholic liver cirrhosis and refractory hyperbilirubinaemia were included in a prospective, double blind, comparative trial. Twenty of them were randomized to methylprednisolone (1 mg/kg/day i.m. over 3 days), and 20 to placebo (saline) of identical shape. In the active group a significant decrease in the bilirubin level (from 248 to 191 mumol/l, a drop by 23%; p < 0.05) was observed, which was not the case in the control group (from 292 to 300 mumol/l, an increase by 2.7%; p > 0.05). A decrease in the alkaline phosphatase activity was observed in both groups (by 11% in the active and by 20% in the control group: p < 0.05) while the encephalopathic indices did not improve in either. It is concluded that a short course of corticosteroid could speed-up the hospital stay and possibly slow down the progression of alcoholic cirrhosis.     

Comparative study of results of hepatic transplantation between 2 groups of patients: alcoholic cirrhosis versus non-alcoholic cirrhosis

Among the patients treated for alcoholic cirrhosis, only a small group could be candidates for liver transplantation (LT). The aim of this multicentric study was to analyse the results of LT in a group of 75 patients with alcoholic cirrhosis (AC) compared with a group of 61 patients with non-alcoholic cirrhosis (NAC). Results were similar in both groups concerning survival rate and quality of life. However the ability to go back to a normal professional life was less in the AC group. The reported recurrence of alcoholic intoxication, which was around 26%, was much lower for patients who interrupted alcohol consumption during at least 3 months before L.T.     

Oxidative stress, antioxidants, and alcoholic liver fibrogenesis

In the intragastric ethanol infusion model using a high fat diet (25% calories as corn oil) and adult Wistar rats, focal centrilobular liver necrosis is evident after five weeks of feeding, and liver fibrogenesis is induced between the 9th and 16th weeks. At the 16th week, fibroproliferative activation of Ito cells, a perisinusoidal cell type believed to be a key player in liver fibrogenesis, can be demonstrated by increased DNA synthesis, enhanced gene expression of collagen, and transforming growth factor-beta 1 (TGF beta 1) by these cells. This stage of alcoholic liver fibrogenesis, but not the earlier stage of liver necrosis, is closely associated with enhanced hepatic lipid peroxidation (LP) as demonstrated by significant correlation between the degree of liver fibrosis and hepatic levels of LP aldehydic products such as malondialdehyde (MDA) and 4-hydroxynonenal (4HNE). The direct role of these aldehydes in alcoholic liver fibrogenesis is supported by in vitro demonstration of stimulation of Ito cell collagen gene expression by MDA and 4HNE as well as in vivo confirmation of the importance of the aldehydes in iron-catalyzed potentiation of alcoholic liver fibrogenesis. Induced cytochrome P4502E1 is considered as a primary site of enhanced oxidative stress, and compromised glutathione homeostasis is suggested to underlie, in part, the net increase in hepatic LP. These findings are in support of our working hypothesis that enhanced LP is a critical pathogenetic event for alcoholic liver fibrogenesis.     

Relation between a dimension of Internal-External Control and the MMPI with an alcoholic population.

Investigated locus of control with the Internal-External Control scale as well as the intercorrelations of this scale with the subscales of the MMPI for 262 alcoholics. Contrary to the initial hypothesis, the alcoholic population scored in the internal control direction. Consistent with the 2nd hypothesis, those alcoholics whose scores were lowest (internal) reported least anxiety, depression, and clinical pathology on the MMPI. Results are discussed in terms of control of reinforcement, i.e., alcohol, and regulation of affective states of distress. (16 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Distribution of peripheral blood lymphoid subsets in alcoholic liver cirrhosis: influence of ethanol intake

The aim of the present study was to investigate the effect of chronic ethanol (EtOH) consumption on the immune system in patients with alcoholic liver cirrhosis (ALC), as analyzed by the distribution of peripheral blood (PB-) T, B, and NK lymphoid subsets using multiple stainings with monoclonal antibodies and flow cytometry. For that purpose, we have analyzed a group of patients with ALC and active EtOH intake (ALCET group) which were re-evaluated 3 months after alcohol withdrawal. As controls, both ALC patients with at least 1 year of alcohol withdrawal (ALCAW group) and healthy subjects were used. Regarding the alcohol intake period, the most relevant findings were a significant activation of the PB T-cell compartment, and specifically of the TCR alpha beta + subset, as reflected by an increased expression of both the HLA DR and CD11c antigens as well as a significant increase of both the PB NK cells (CD3-/CD56+) and the cytotoxic T cells coexpressing the CD3 and CD56 molecules. In addition, a decrease of both the numbers of total B cells and their CD5+/CD19+ subset were observed. After a relatively short withdrawal period (3 months), the abnormalities of T, P, and NK cells disappeared. These findings suggest the existence of a close relationship between EtOH consumption and the abnormalities of the immune system observed during active alcoholism. Nevertheless, ALCAW individuals displayed marked alterations on the immunophenotypic profile, as reflected by a significantly decreased number of total T cells, due to reduced levels of the CD3+/TCR alpha beta+, CD4+, CD8+, and CD4+/CD45RA+ T-cell subsets. In addition, a significantly decreased number of total PB B cells was observed in this group of patients. Our results show that in patients suffering from ALC, the abnormalities of the immune system due to a direct effect of EtOH intake (or its metabolites) should be distinguished from the immunological alterations related to the liver disease itself.     

Effect of the type of beverage and meat consumed by alcoholics with alcoholic liver disease

We analyzed meat products and alcoholic beverage preference in patients with the three stages of alcoholic liver disease (ALD) compared with controls using diet history data. Daily consumption of total alcohol, types of alcoholic beverages, and types of meat and meat products in grams was obtained by dietary history taken from patients with biopsy proven stage of ALD. A strong association was found between the ALD subjects and total alcohol and beer consumption. There was a significant increase in the consumption of total pig products, pork, and offal in the ALD groups compared with controls. There was a significant positive correlation between beer consumption and pork in alcoholic hepatitis, total pork products in alcoholic hepatitis, and cirrhosis and offal in alcoholic hepatitis and cirrhosis. There was no correlation with the fatty liver stage of ALD. The strongest correlation was between beer and total pig products in the alcoholic hepatitis group. Wine consumption was negatively correlated with the consumption of pig products and beer in the alcoholic cirrhosis group. In conclusion, the association of total pig product consumption with cirrhosis mortality in various countries was validated by personal diet history data obtained from ALD patients in a tested clinical microcosm. The results suggest that this association may be modified by the type of alcoholic beverage that is preferentially consumed.     

The relationship between drinking control strategies and college student alcohol use.

Interventions designed to reduce heavy drinking among college students often contain suggestions for drinking control strategies. However, little is known about the relationship between the use of these strategies and alcohol consumption. The authors developed a measure of drinking control strategies and investigated its psychometric properties in a sample of 250 college drinkers. Strategies clustered into three factors: selective avoidance of heavy drinking activities and situations, strategies used while drinking, and alternatives to drinking. These three types of strategies were independently associated with alcohol use; however, the first and last types were negatively associated with alcohol consumption, whereas the second type was positively associated with alcohol use. The findings from this study suggest that the type of strategy recommended may be important when the goal is alcohol reduction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Loneliness, social drinking, and vulnerability to alcohol problems.

Investigated the relationship between dispositional loneliness (representing deficient social skills, absence of supportive social relationships, and negative introspection), vulnerability to alcohol problems, and locus of control. 99 Ss (mean age 26.12 yrs) completed the Revised UCLA Loneliness Scale (UCLA) measures of drinking and locus of control (i.e., fatalism, self-control, social system control). UCLA scores were strongly related to adverse consequences of drinking, perceived problem-drinker status, and coping functions. Both loneliness and alcohol problems were related to external locus of control over personal consequences and impulses. Loneliness is discussed as a source of differential vulnerability to alcohol problems among relatively heavy drinkers due to a lack of social supports and different perceptions of social pressures. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

College drinking behaviors: Mediational links between parenting styles, parental bonds, depression, and alcohol problems.

Mediational links between parenting styles (authoritative, authoritarian, permissive), parental bond (positive, negative), depression, alcohol use and abuse were tested. A 2-group, multiple-indicator, multiple-cause structural equation model with 441 (216 female, 225 male) college students was examined. In general, a poor parental bond with one's father was highly predictive of depression, a well-known predictor of alcohol abuse and related problems for both genders. In contrast, a positive parental bond with one's father significantly mediated the positive effects of authoritative fathering on depression, which then decreased alcohol use problems for both genders. For women, a negative parental bond with one's father significantly mediated the effect of having an authoritarian father on depression, which increased alcohol use problems. These findings suggest that parental influences on pathways to alcohol abuse through depression (primarily through fathers for both genders) are distinct from pathways stemming from poor impulse control (with influences primarily from the same-sex parents for both genders). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relation of endothelins to volume regulating neurohumoral systems in patients with cirrhosis of the liver

The aim of the present study was to investigate the relationship between ET plasma concentrations and other hormonal systems in acute volume regulation of patients with cirrhosis. Ten healthy controls and 10 cirrhotic patients, five without and five with ascites were studied after 1 h in a sitting posture and subsequently subjected to 1 h head-out water immersion. Blood was collected for determinations of ET-1, ET-3, ANF, aldosterone, renin activity and noradrenaline. In addition, in 10 patients with compensated cirrhosis the effect of loop diuretics on ET-3, aldosterone and renin was studied. ETs in cirrhosis were significantly (P < 0.01) higher than in controls both before (ET-1, 19.6 +/- 1.3 pgmL-1 vs. 11.8 +/- 0.4 pgmL-1; ET-3, 18.5 +/- 1.4 pgmL-1 vs. 9.5 +/- 0.5 pgmL-1) and after water immersion (ET-1, 18.6 +/- 1.2 pgmL-1 vs. 12.4 +/- 0.3 pgmL-1; ET-3, 18.7 +/- 1.7 pgmL-1 vs. 10.0 +/- 0.5 pgmL-1). In cirrhotic patients, basal and immersion concentrations of ET-1 were significantly correlated to noradrenaline plasma concentrations (r = 0.79, P < 0.05). ET-3 plasma concentrations in cirrhosis were correlated to renin activity (r = 0.65, P < 0.05). Furthermore, ET-3 in cirrhosis was inversely correlated to systolic and mean arterial blood pressure (r = -0.55, P < 0.01 and r = -0.50, P < 0.05; respectively). To investigate the effect of hypovolaemia in compensated cirrhosis, 10 patients without ascites were studied before and after treatment with loop diuretics. In compensated cirrhosis ET-3 was significantly increased 6h after oral diuretic treatment (17.9 +/- 1.0 pgmL-1 vs. 15.5 +/- 0.4 pgmL-1, P < 0.001). The presented data demonstrate relations of endothelins, particularly of ET-3 to neurohumoral systems in patients with cirrhosis of the liver.