Lifetime drinking history in patients with alcoholic liver disease and patients with alcohol use disorder without liver disease

Objective: To determine the differences in lifetime alcohol intake (LAI) and drinking patterns between patients with alcoholic liver disease (ALD) and alcohol use disorder (AUD) without notable liver injury and between males and females with ALD.

Methods: Alcohol drinking patterns were assessed using the Lifetime Drinking History (LDH) a validated questionnaire, during an outpatient visit. Patients with AUD, currently in addiction treatment, were matched for gender and age (±5 years) with the ALD group.

Results: A total of 39 patients with ALD (26 males and 13 females; median age 58) and equal number of AUD patients were included (median age 56 years). The onset age for alcohol drinking and duration of alcohol consumption was similar in ALD and AUD. The number of drinking days was higher in women with ALD than in women with AUD: 4075 [(3224–6504) versus 2092 (1296–3661), p?=?.0253]. The LAI and drinks per drinking day (DDD) were not significantly different between patients with ALD and AUD. Females with ALD had lower LAI than males with ALD: 32,934 (3224–6504) versus 50,923 (30,360–82,195), p?=?.0385, fewer DDD (p?=?.0112), and lower proportion of binge drinking as compared to males with ALD (p?=?.0274).

Conclusions: The total LAI was similar in patients with ALD and AUD. The number of drinking days over the lifetime was associated with the development of ALD in females. Females with ALD had significantly lower alcohol consumption than men with ALD despite similar duration in years of alcohol intake which supports the concept of female propensity of ALD.     

Hepatic alcohol dehydrogenase activity in alcoholic subjects with and without liver disease

Alcohol dehydrogenase activity was measured in samples of liver tissue from a group of alcoholic and non-alcoholic subjects to determine whether decreased liver alcohol dehydrogenase activity is a consequence of ethanol consumption or liver damage. The alcoholic patients were classified further into the following groups: control subjects with no liver disease (group 1), subjects with non-cirrhotic liver disease (group 2), and subjects with cirrhotic liver disease (group 3). The non-alcoholic subjects were also divided, using the same criteria, into groups 4, 5, and 6, respectively. The analysis of the results showed no significant differences when mean alcohol dehydrogenase activities of alcoholic and non-alcoholic patients with similar degrees of liver pathology were compared (groups 1 v 4, 2 v 5, and 3 v 6. Alcohol dehydrogenase activity was, however, severely reduced in patients with liver disease compared with control subjects. Our findings suggest that alcohol consumption does not modify hepatic alcohol dehydrogenase activity. The reduction in specific alcohol dehydrogenase activity in alcoholic liver disease is a consequence of liver damage.     

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.     

Plasma homocysteine and lipoprotein profile in patients with peripheral arterial occlusive disease

Several studies have identified moderate hyperhomocysteinemia (HCy) as an independent risk factor for atherosclerosis. The purpose of this case control study was to determine lipoprotein profile and homocysteine concentration in serum of 85 male patients with peripheral arterial occlusive disease (PAOD) and in 51 normolipidemic age-matched male controls. Cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol as well as subfractions HDL2 and HDL3 cholesterol, low-density lipoprotein (LDL) cholesterol, apo B, apo A-I, and lipoprotein particles LpA-I and LpA-I:A-II were measured in serum. Homocysteine, folic acid, and vitamins B6 and B12 were determined with the help of high-pressure liquid chromatography. The 677 C --> T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene was analyzed in PAOD patients. Patients with peripheral arterial occlusive disease showed a significantly higher mean concentration of homocysteine than control subjects (p<0.001). There was a negative correlation between the levels of homocysteine and vitamin B12 as well as folic acid (for vitamin B12: r=-0.40 and for folic acid: r=-0.38). The prevalence of hyperhomocysteinemia (Hcy >16 micromol/L) in the patients was 45% in contrast to 8% in controls. HDL cholesterol, HDL3 cholesterol, Apo A-I, and Lp A-I were significantly reduced in patients and triglycerides were elevated. The elevated plasma homocysteine concentration is frequently seen in homozygous carriers of a point mutation (677 C --> T) in the methylenetetrahydrofolate reductase gene, as the product of this gene is an enzyme, participating in homocysteine remethylation. The homozygous state for the 677 C --> T mutation was found in 13.3% of PAOD patients.     

Changes in serum apolipoprotein and lipoprotein profile after alcohol withdrawal: effect of apolipoprotein E polymorphism

BACKGROUND: Apolipoprotein (Apo) E genotype and alcohol consumption or withdrawal strongly affect lipoprotein (Lp) metabolism and, as with any genetic and environmental factors, they might interact. The aim of this study was to investigate this gene/environment interaction by analyzing the effect of the apoE genotype on the alcohol withdrawal-induced alterations in the serum Apo and Lp profile. METHODS: ApoE genotypes and concentrations of serum cholesterol, triglyceride, and Lps containing apoA-I, A-II, B, E, and C-III were determined in 84 male alcohol abusers before and after 3 weeks of abstinence. RESULTS: After withdrawal, concentrations of serum apoA-I, LpA-I, LpA-I/A-II, apoC-III, LpC-III-non-B, apoE, and LpE-non-B significantly decreased, whereas those of triglycerides and apoB increased; levels of cholesterol, LpC-III:B, and LpB:E were not affected. ANOVA shows that apoE polymorphism effects were quite similar before and after alcohol withdrawal on all serum Apos and Lps (the interaction term between withdrawal and apoE genotype was not significant). The only interaction term that was borderline significant (p < or = 0.10) concerned the apoB concentration. Before withdrawal, no association between apoB level and apoE polymorphism was observed, whereas after abstinence, a borderline significant (p < or = 0.10) gradient of concentration across the three groups of subjects (epsilon2 carriers < epsilon3/epsilon3 < epsilon4 carriers) was noticed. CONCLUSIONS: Alcohol abstinence causes major changes in the antiatherogenic Apos and Lps and may increase those known to be atherogenic. Heavy alcohol consumption seems to alter the effect of apoE polymorphism on apoB levels, and further investigations are needed to clarify the mechanisms involved in this phenomenon: a defect in sialylation of apoE, formation of acetaldehyde adducts on apoB, or both.     

Pattern of psychiatric morbidity and alcohol dependence in patients with alcoholic liver disease

Fifty-six male patients with alcoholic liver disease were evaluated for the presence and severity of alcohol dependence and psychiatric illness using a severity of alcohol dependence questionnaire and research diagnostic criteria, respectively. Forty-three (76.7%) patients were found to be dependent; 26 (46.4%) moderately, and 17 (30.3%) severely. Patients with alcoholic hepatitis were significantly (P less than 0.05) more often found to be dependent than patients with alcoholic cirrhosis. Psychiatric morbidity was observed in 42 (75%) of the patients with alcoholic liver disease and 15 (26.7%) of the nonalcoholic cirrhotics. The difference was highly significant (P less than 0.01). The commonest disorders in patients with alcoholic liver disease were neuroses (33.0%), followed by affective disorders (26.8%). It was, however, not possible to ascertain whether psychiatric disorders antedated alcoholism or were secondary to it. Detection of moderate to severe dependence on alcohol and psychiatric morbidity in about three-fourths of the patients with alcoholic liver disease warrants an increased awareness and a multidisciplinary approach for the management of these patients.     

Antibodies to alcohol altered liver cell determinants in patients with alcoholic liver disease.

Circulating antibodies reacting specifically with hepatocytes isolated from ethanol pretreated rabbits have been demonstrated by two techniques - induced cytotoxicity and immunofluorescence. In the cytotoxicity assay antibodies were found in seven of 19 (39%) of patients with alcoholic fatty liver (with or without fibrosis), six of 13 (46%) of those with alcoholic hepatitis, 15 of 36 (43%) of those with cirrhosis, and seven of 14 patients (50%) of those with hepatitis and cirrhosis. In the immunofluorescence studies, nine of 15 sera induced a granular pattern of fluorescence on the ethanol pretreated hepatocytes; two sera which induced significant cytotoxicity did not induce immunofluorescence. No ethanol related antibodies were found in normal individuals or in patients with other types of acute or chronic liver disease. These results show that antibodies directed against ethanol altered liver cell determinants are present in the serum of 43% of patients with alcoholic liver disease, and suggest a mechanism whereby chronic alcohol consumption may, by inducing antigenic changes in hepatocyte membranes, trigger a cell damaging immune reaction.     

Socioeconomic impact of alcohol in patients with alcoholic liver disease in eastern India

Aim

The aim of this study is to estimate the socioeconomic impact of alcohol use on patients with alcoholic liver disease (ALD) and their families.

Methods

The demographic and socioeconomic data were collected from hospitalized ALD patients and attendants using a self designed non validated questionnaire and analyzed.

Results

Study subjects included 100 consecutive ALD patients (all males). Sixty percent were between 30 and 50 years. Most were married (96 %), literate (63 %), either businessmen (37 %) or employed (30 %) and belonged to middle socioeconomic class. Ninety percent started alcohol use before age 30 years and half during teenage. Mean alcohol intake was 190 mL/day (mean duration 23 years); 60 % consumed alcohol daily. Concomitant tobacco abuse was noted in 79 %. Average expenditure on alcohol was Rs 3800/month. Average hospitalizations for ALD related problems was 2.6 times/year with average expenditure of INR 30,000 (~440 US$) during each hospitalization. For treatment expenses, 86 % of patients borrowed money from friends/relatives, 36 % used saving deposits, and 4 % sold personal belongings. Eleven percent lost their job, and 7 % sold immovable property. In 43 % of cases, children were deprived of education. Besides, 52 % had disturbed social and family life, 34 % abused their spouse, 20 % suffered accidents, and 37 % indulged in physical violence.

Conclusion

Majority of ALD patients and their families had disturbed social and family life and incurred severe financial loss arising of alcohol use.

     

Identification of alcoholic liver disease or hidden alcohol abuse in patients with elevated liver enzymes

Abstract. The aim of this prospective study was to identify alcoholic liver disease or covert alcohol abuse in unselected consecutive patients referred to a gastroenterologic out-patient's clinic for elevated liver enzymes. One-hundred-and-thirteen patients were questioned about alcohol consumption, trauma history and loss of driver's licence. Laboratory tests claimed to reflect alcohol consumption and liver biopsy were taken. Using data from patients with the highest (26 patients) and lowest (29 patients) stated consumptions, logistic regression analysis identified violence score (trauma score + driver's licence score) and a laboratory index combining MCV, ASAT/ALAT ratio and IgA values as significant independent predictors of alcohol abuse (index = 2.3 × violence score + 1.08 × laboratory index— 3.19). Twenty-six patients openly admitted alcohol abuse (> 300 g week^?1) and 85% of these had alcoholic liver damage. The index identified a further 12 patients as abusers who stated an intermediate alcohol consumption (25–300 g week^?1). Half of these had alcoholic liver damage. Thus, a total of 34% of the patients were identified as abusers and in one-third of these the abuse was covert.     

Left ventricular performance in alcoholic patients without chronic liver disease

Left ventricular performance was studied non-invasively in 24 chronic alcoholics without liver disease. Twelve patients who had abstained from drinking for at least one month (group A) and 12 sex and age matched patients who had ceased drinking during the preceding 24 hours (group B) were studied at rest and during 50% submaximal exercise. Cardiac output and stroke volume were measured by first passage and left ventricular ejection fraction by multigated radionuclide cardiography. Twelve healthy sex and age matched controls were also studied. Haemodynamic variables were similar in group A and the controls, except that in group A left ventricular end systolic volume index did not decrease during exercise. In group B the heart rate was increased both at rest and during exercise and plasma noradrenaline concentrations were increased. The stroke volume index did not increase significantly during exercise in group B. In addition, the increase in left ventricular ejection fraction was smaller in group B than in controls. End systolic contraction was reduced in group B patients and diastolic blood pressure was increased. These results suggest that cardiac abnormalities in chronic alcoholics may be reversed after cessation of drinking if no chronic liver disease is present. Recent alcohol consumption increases sympathetic nervous activity, impairs cardiac contractility, and increases afterload during physical stress.     

Left ventricular performance in alcoholic patients without chronic liver disease.

Left ventricular performance was studied non-invasively in 24 chronic alcoholics without liver disease. Twelve patients who had abstained from drinking for at least one month (group A) and 12 sex and age matched patients who had ceased drinking during the preceding 24 hours (group B) were studied at rest and during 50% submaximal exercise. Cardiac output and stroke volume were measured by first passage and left ventricular ejection fraction by multigated radionuclide cardiography. Twelve healthy sex and age matched controls were also studied. Haemodynamic variables were similar in group A and the controls, except that in group A left ventricular end systolic volume index did not decrease during exercise. In group B the heart rate was increased both at rest and during exercise and plasma noradrenaline concentrations were increased. The stroke volume index did not increase significantly during exercise in group B. In addition, the increase in left ventricular ejection fraction was smaller in group B than in controls. End systolic contraction was reduced in group B patients and diastolic blood pressure was increased. These results suggest that cardiac abnormalities in chronic alcoholics may be reversed after cessation of drinking if no chronic liver disease is present. Recent alcohol consumption increases sympathetic nervous activity, impairs cardiac contractility, and increases afterload during physical stress.     

Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease: reevaluation with an improved chromogenic assay

Plasma endotoxin concentration was measured in 85 patients with alcoholic liver disease (alcoholic cirrhosis (n = 64), alcoholic hepatitis without cirrhosis (n = 11), fatty liver (n = 10), and in patients with non-alcoholic cirrhosis (n = 15]. Endotoxin concentration was determined with an improved chromogenic substrate assay, using individual standard curves for each plasma sample. In patients with alcoholic cirrhosis the mean endotoxin concentration was significantly higher than in patients with non-alcoholic cirrhosis (p less than 0.05). In addition, distinctly higher endotoxin concentrations (greater than 20 pg/ml) were more frequently observed in patients with alcoholic cirrhosis than in non-alcoholic cirrhosis (34.4 vs. 14.3%, p less than 0.05). Mean endotoxin concentration was not significantly higher in cirrhotics with ascites or esophageal varices as compared with the subgroup without ascites or esophageal varices. The endotoxin concentration did not correlate with serum bilirubin, prothrombin concentration or serum enzyme activities. In patients with alcoholic liver disease, however, endotoxin concentration revealed a negative correlation (p less than 0.05) with the concentration of high density lipoprotein cholesterol. On admission endotoxin concentrations in alcoholics with fatty liver were similarly elevated as observed in alcoholic cirrhosis. In six out of 12 patients with fatty liver or alcoholic hepatitis, in whom a second sample of plasma was investigated after 6 to 8 days, endotoxemia was no longer detectable; in the remaining patients, the endotoxin concentration decreased markedly. The results indicate that, irrespective of the stage of liver disease, alcohol abuse favours the development of endotoxemia. They support the hypothesis that gut-derived endotoxins might play a role in the initiation and aggravation of alcohol-induced liver disease.     

Concentrations of apolipoprotein AI,AII, and E in plasma and lipoprotein fractions of alcoholic patients: Gender differences in the effects of alcohol

Previous studies have shown that plasma levels of high-density lipoprotein (HDL) cholesterol and the two major protein components of HDLs, i.e., apolipoproteins AI and AII, were elevated in male alcoholic patients without serious liver injury. By contrast, alcohol effect on apolipoprotein E remains unclear. Apolipoprotein E is a major component of very low-density lipoprotein (VLDL) and a minor component of human high-density lipoprotein. It plays a critical role in lipoprotein metabolism through cellular lipoprotein receptors. Furthermore, previous works were carried out mostly with male subjects, whereas alcohol effects on serum apolipoproteins in female subjects have not yet been adequately addressed. In this study, we have raised antibodies specifically to recognize human apolipoprotein AI, All, and E, respectively, to quantify apolipoprotein concentrations in plasma and lipoprotein fractions of male and female alcoholic patients. We have also measured plasma apolipoprotein concentrations in patients who had abstained from alcohol while in the hospital. Our results showed the following: (1) plasma concentrations of apolipoprotein AI and All were significantly elevated yet plasma apolipoprotein E decreased (33%) significantly (P < .01) in male alcoholic patients; (2) apolipoprotein AI concentrations in female nondrinking control subjects were higher than in male controls, and the concentrations of apolipoprotein AI in female alcoholic patients were not significantly elevated over those of female controls; (3) similar to their male counterparts, female alcoholic patients exhibited higher plasma apolipoprotein All and lower apolipoprotein E; (4) changes in plasma apolipoproteins seen here were most likely attributable to a direct effect of alcohol but not a secondary effect of mild liver injury; (5) changes in plasma apo lipoprotein levels in alcoholic patients were reversible in 1 week after alcohol abstinence; and (6) the decrease of plasma apo E in alcoholic patients was indicated by the presence of apo E-deficient VLDL particles whereas the concentration of apo E in HDL particles of alcoholic patients remained unaffected.     

Plasma apolipoprotein C-III transport in centrally obese men: associations with very low-density lipoprotein apolipoprotein B and high-density lipoprotein apolipoprotein A-I metabolism

CONTEXT: Apolipoprotein (apo) C-III is associated with hypertriglyceridemia and progression of cardiovascular disease. Plasma apoC-III is elevated in centrally obese men, and we hypothesized that the kinetics of apoC-III are disturbed in these subjects. OBJECTIVE: We developed a compartmental model to determine very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) apoC-III metabolic parameters in centrally obese men and investigated the associations with VLDL-apoB and HDL-apoA-I kinetics. STUDY DESIGN: Apolipoprotein kinetics was determined using stable isotope techniques and compartmental modelling in 39 centrally obese and 12 nonobese men. RESULTS: Compared with nonobese subjects, centrally obese subjects had increased plasma apoC-III concentration (160 +/- 5 mg/liter vs. 103 +/- 9 mg/liter, P < 0.001), reflecting increased concentrations of both VLDL-apoC-III and HDL-apoC-III. These related to increased production rate (PR) of VLDL-apoC-III (2.12 +/- 0.14 vs. 1.56 +/- 0.29 mg/kg x d, P < 0.05) and reduced fractional catabolic rate (FCR) of both VLDL- and HDL-apoC-III (0.70 +/- 0.02 pools/d vs. 0.82 +/- 0.05 pools/d, P < 0.05). In centrally obese men, VLDL-apoC-III concentration was significantly (P < 0.05) associated with VLDL-apoB concentration and PR as well as HDL-apoA-I FCR and PR and inversely with VLDL-apoB FCR. HDL-apoC-III concentration was significantly (P < 0.05) associated with the concentrations of both VLDL-apoB and HDL-apoA-I, the FCR, and the PR of HDL-apoA-I and inversely with the VLDL-apoB FCR. In multiple regression analysis, both VLDL-apoC-III and HDL-apoC-III concentrations were significantly associated with HDL-apoA-I FCR. CONCLUSIONS: In centrally obese men, elevated VLDL-apoC-III and HDL-apoC-III concentrations are a consequence of elevated production and decreased catabolism of VLDL-apoC-III and reduced catabolism of HDL-apoC-III, respectively. These defects are associated with disturbances in VLDL-apoB and HDL-apoA-I metabolism.     

Outcome of liver transplantation in patients with alcoholic liver disease

BACKGROUND: Liver transplantation is accepted as effective therapeutic option for end-stage liver disease, including alcoholic liver disease AIM: To evaluate the outcome of liver transplantation for alcoholic liver disease in the Liver Transplantation Program at "Hospital de Clínicas" of the Federal University of Paraná, Curitiba, PR, Brazil. PATIENTS AND METHODS: It was performed a retrospective study of the patients who underwent liver transplantation for alcoholic end-stage liver disease between September 1991 and January 2001. The minimum abstinence period required was 6 months before liver transplantation. Identification of alcohol consumption after liver transplantation was determinated by information provided by patient or family and biochemical or histological anormalities. RESULTS: Twenty patients underwent liver transplantation for alcoholic liver disease in the study period, 95% (19/20) were men and the median age was 50 years (29-61 years). Seventy-five percent of the patients (15/20) had severe liver disfunction (Child C class) in the pre-transplant period. In six of them (30%) there was association with viral hepatitis and in one, with hepatocarcinoma. Median abstinence period before liver transplantation was 24 months, varying from 9 to 120 months. One-year and 3-year survival rate were 75% and 50%, respectively. The main complications were: acute cellular rejection (40%), chronic rejection (5%), hepatic artery thrombosis (15%), biliary complications (15%), bacterial or fungal infections (45%), cytomegalovirus infection (20%). Three patients returned to alcohol use after liver transplantation CONCLUSION: The survival of patients who received liver transplant for alcoholic cirrhosis are satisfactory. In the present study there was a small index of alcohol use after liver transplantation.