Alcoholic Cirrhotics Research Articles

Randomized, double-blind, placebo controlled trial of RHU-EPO to improve platelet count and platelet function in alcoholic cirrhotics with thrombocytopenia

Randomized, double-blind, placebo controlled trial of RHU-EPO to improve platelet count and platelet function in alcoholic cirrhotics with thrombocytopenia

Thiamine deficiency in hepatitis C virus and alcohol-related liver diseases.

Thiamine deficiency is a common feature in chronic alcoholic patients, and its pathophysiology remains poorly understood. Until now, thiamine deficiency has been considered to be mainly the result of alcoholism irrespective of the underlying liver disease. The aims of the study were to compare the prevalence of thiamine deficiency in alcohol- and hepatitis C virus-(HCV-) related cirrhosis and in patients with chronic hepatitis C without cirrhosis. Forty patients with alcoholic cirrhosis (group A), 48 patients with HCV-related cirrhosis (group B), and 59 patients with chronic hepatitis C without cirrhosis (group C) were included prospectively. Thiamine status was evaluated by concomitant determination of erythrocyte transketolase activity, thiamine diphosphate (TDP) effect, and direct measurement of erythrocyte thiamine and its phosphate esters by HPLC. Thiamine was mainly present in erythrocytes in its diphosphorylated form. Prevalence of thiamine deficiency and levels of TDP in thiamine-deficient patients were similar in patients of group A (alcoholic cirrhosis) and of group B (viral C cirrhosis). None of the patients with chronic hepatitis (group C) was deficient. Thiamine deficiency was not correlated with the severity of the liver disease or disease activity. No impairment of thiamine phosphorylation was found in the three groups. conclusion, alcoholic or HCV-related cirrhotics have the same range of thiamine deficiency, while no patient without cirrhosis has thiamine deficiency, and impaired phosphorylation does not account for the deficiency observed in cirrhotics. We suggest that thiamine should be given to patients with cirrhosis irrespective of its cause.

Histological features after liver transplantation in alcoholic cirrhotics

Background/Aims : Though alcoholic cirrhosis is a common indication for liver transplantation, it carries the risk of alcohol recidivism and consequent graft failure. This study aims to evaluate the effect of alcohol recidivism on survival rates and histological parameters in patients transplanted for alcoholic cirrhosis, with and without hepatitis C virus (HCV) infection. Methods : Fifty-one out of 189 consecutive transplanted patients underwent psychosocial evaluation and liver biopsy at 6 and 12 months, then yearly after transplantation. Results : The cumulative 84 month survival rate was identical in patients transplanted for alcoholic (51%) and non-alcoholic cirrhosis (52%). No difference emerged between anti-HCV negative vs. positive alcoholic cirrhosis patients. Psycho-social evaluation revealed alcohol recidivism in 11/34 long-term survivors, but this did not affect overall survival rate in patients with or without HCV. In anti-HCV negative cases, fatty changes and pericellular fibrosis were significantly more common in heavy drinkers than in occasional drinkers and abstainers. When HCV status was considered regardless of alcohol intake, fibrosis was significantly more frequent in patients with HCV. Conclusion : Alcohol recidivism after transplantation in alcoholic cirrhosis patients does not affect survival, irrespective of HCV status. Fatty changes and pericellular fibrosis are the most relevant histological signs of heavy alcohol intake.

Evidence of an increased nitric oxide production in primary biliary cirrhosis

OBJECTIVE: Although possible implications of nitric oxide in the pathophysiology of liver cirrhosis have been extensively studied, until now few articles have addressed the assessment of nitric oxide production in primary biliary cirrhosis. This study was directed to evaluate circulating nitrosyl-hemoglobin levels as well as neutrophil elastase and soluble adhesion molecule concentrations in this condition, by assuming these parameters as possible markers of either inflammatory response or neutrophil activation. METHODS: Laboratory investigations were performed in 30 patients with primary biliary cirrhosis, in 13 patients with postviral and/or alcoholic cirrhosis, and in a group of eight subjects with chronic hepatitis. RESULTS: Although no difference was detected with respect to chronic hepatitis subjects, higher levels of nitrosyl-hemoglobin adducts were found in primary biliary cirrhosis patients than in postviral or alcoholic cirrhotics and in normal subjects (3.55 ± 1.75 arbitrary units vs 1.95 ± 0.57 and 0.84 ± 0.34, p = 0.0004 and p < 0.0001, respectively). Similarly, more elevated concentrations of neutrophil elastase (213.7 ± 192.0 μg/L vs 51.1 ± 34.3 and 38.0 ± 11.5, p < 0.0001 and p < 0.0001, respectively) as well as of soluble forms of intercellular adhesion molecule 1 and endothelial-leukocyte adhesion molecule 1 were shown in primary biliary cirrhosis patients than in subjects with cirrhosis of other etiologies and in controls. CONCLUSIONS: Highly enhanced nitric oxide production in primary biliary cirrhosis could be related to the development of strong inflammation and at least partially to neutrophil activation, thus suggesting a putative role of these cellular mediators in the development of liver damage owing to their ability to synthesize and release a wide variety of important factors, including elastase and nitric oxide.

Evidence of an increased nitric oxide production in primary biliary cirrhosis.

Although possible implications of nitric oxide in the pathophysiology of liver cirrhosis have been extensively studied, until now few articles have addressed the assessment of nitric oxide production in primary biliary cirrhosis. This study was directed to evaluate circulating nitrosyl-hemoglobin levels as well as neutrophil elastase and soluble adhesion molecule concentrations in this condition, by assuming these parameters as possible markers of either inflammatory response or neutrophil activation. Laboratory investigations were performed in 30 patients with primary biliary cirrhosis, in 13 patients with postviral and/or alcoholic cirrhosis, and in a group of eight subjects with chronic hepatitis. Although no difference was detected with respect to chronic hepatitis subjects, higher levels of nitrosyl-hemoglobin adducts were found in primary biliary cirrhosis patients than in postviral or alcoholic cirrhotics and in normal subjects (3.55+/-1.75 arbitrary units vs 1.95+/-0.57 and 0.84+/-0.34, p = 0.0004 and p < 0.0001, respectively). Similarly, more elevated concentrations of neutrophil elastase (213.7+/-192.0 microg/L vs 51.1+/-34.3 and 38.0+/-11.5, p < 0.0001 and p < 0.0001, respectively) as well as of soluble forms of intercellular adhesion molecule 1 and endothelial-leukocyte adhesion molecule 1 were shown in primary biliary cirrhosis patients than in subjects with cirrhosis of other etiologies and in controls. Highly enhanced nitric oxide production in primary biliary cirrhosis could be related to the development of strong inflammation and at least partially to neutrophil activation, thus suggesting a putative role of these cellular mediators in the development of liver damage owing to their ability to synthesize and release a wide variety of important factors, including elastase and nitric oxide.

DRINKING PATTERNS AND BEVERAGE PREFERENCES OF LIVER CIRRHOSIS PATIENTS IN MEXICO

The purpose of this study was to investigate the pattern of alcoholism in a special group of alcoholics (alcoholic cirrhotics) in a hospital-based population in west central México and assess the role of regional spirits such as tequila. A complete alcohol drinking history and a structured questionnaire directed at investigating the pattern of alcohol consumption was applied to124 adult patients with chronic liver disease caused by alcohol during January1995 to January 1996.The mean age of onset was 27 ± 3 years in women and 18 ± 0.5 years in men. The mean alcohol intake per week was 749 ± 192g for women and 1113 ± 151g for men. On average, patients consumed alcohol for a mean of 24.5 years. The overall patient drinking preference was for tequila followed by 96° Gay Lusac (G.L.), alcohol, and beer. In a subset of 70 patients three phases of alcoholism could be identified (prealcoholic, critical, and chronic). Each phase had a mean duration of at least 11 years.Beer was the dominant beverage in the prealcoholic phase while tequila was consumed more often in the other phases. In the critical phase of alcoholism an average of 337g of alcohol were consumed per week and in the chronic phase1765g/week.Tequila was the overall preferred beverage in this group of alcoholics.Other beverages included beer and straight alcohol with a clear trend from less to higher concentration of alcohol throughout the drinking history. Subtle gender differences in the patterns of alcoholism may be suspected. In this group of patients the role of tequila drinking is highlighted.

Autonomic dysfunction and cholelithiasis in patients with cirrhosis.

Gallstones are seen in 33-46% of patients with cirrhosis, and their prevalence is known to increase with the duration and severity of liver disease. We hypothesized that autonomic neuropathy may contribute to the formation of gallstones or gallbladder disease, as in diabetics with autonomic neuropathy, due to impaired gallbladder emptying. The objective of our study was to determine the prevalence of gallstones or gallbladder disease in cirrhotic patients with and without autonomic neuropathy. We determined autonomic function tests, gallstones, and other gallbladder disease in 123 (male 71) with varying severity of liver disease (Child classes: A, 40; B, 45; C, 35). In all, 54 patients had gallstones and an additional 22 patients had other gallbladder disease (cholecystitis, common bile duct stones, or debris). Autonomic neuropathy was seen in 97 patients (one abnormal test in 48 and two or more in 49). The prevalence of gallstones was similar in Child A (57%), Child B (64%), and Child C (63%) cirrhosis. The gallstones or gallbladder disease was not increased in women, blacks, diabetics, or alcoholic cirrhotics. The prevalence of gallbladder disease was increased in patients with autonomic neuropathy (51% vs 35%, P = 0.08); in patients with Child C cirrhosis, gallstones (P = 0.018) and gallbladder disease (P = 0.03) were seen more commonly in patients with autonomic neuropathy. Our findings suggest that autonomic neuropathy may contribute to the formation of gallstones in patients with advanced cirrhosis, perhaps by impairing gallbladder and sphincter of Oddi dysmotility.

Bacterial infection in cirrhotic patients and its relationship with alcohol.

Infections are regarded as a major complication and an important cause of death in cirrhotics. Alcohol is a predisposing factor to infections in such patients. This study was undertaken to compare the frequency and evolution of bacterial infection among alcoholic and nonalcoholic cirrhotics. To observe this relationship, we retrospectively studied a cohort of 382 cirrhotic inpatients, 201 of whom were alcoholic (alcohol intake > or =80 g/day for > or =10 yr) and 181 of whom were nonalcoholic. A total of 128 (33.5%) patients presented with infection upon hospitalization, 78 of whom were alcoholic and 50 of whom were nonalcoholic (p = 0.02). A total of 157 cases of infection were diagnosed, with spontaneous bacterial peritonitis as the most prevalent one (54.1%), followed by pneumonia (18.5%), infection of the soft parts (10.8%), and urinary tract infection (7.0%). Infection and deaths were more frequent in patients with Child-Pugh C than in those with Child-Pugh A/B (p = 0.003, p = 0.0002 respectively). Alcoholic patients with Child-Pugh A/B were more susceptible to infection compared to nonalcoholic patients (p = 0.02), although no difference was noted as to the number of deaths (p = 0.1). With regard to patients with Child-Pugh C, no statistical difference was found in the infections or deaths among alcoholics and nonalcoholics (p = 0.8, p = 0.8). Our findings suggest that, despite the fact that bacterial infections are more common in cirrhotic alcoholics, its seems that the mortality rate is associated more with the severity than with the etiology of the hepatic disease.

Bacterial infection in cirrhotic patients and its relationship with alcohol

OBJECTIVE: Infections are regarded as a major complication and an important cause of death in cirrhotics. Alcohol is a predisposing factor to infections in such patients. This study was undertaken to compare the frequency and evolution of bacterial infection among alcoholic and nonalcoholic cirrhotics. METHODS: To observe this relationship, we retrospectively studied a cohort of 382 cirrhotic inpatients, 201 of whom were alcoholic (alcohol intake ≥80 g/day for ≥10 yr) and 181 of whom were nonalcoholic. RESULTS: A total of 128 (33.5%) patients presented with infection upon hospitalization, 78 of whom were alcoholic and 50 of whom were nonalcoholic ( p = 0.02). A total of 157 cases of infection were diagnosed, with spontaneous bacterial peritonitis as the most prevalent one (54.1%), followed by pneumonia (18.5%), infection of the soft parts (10.8%), and urinary tract infection (7.0%). Infection and deaths were more frequent in patients with Child-Pugh C than in those with Child-Pugh A/B ( p = 0.003, p = 0.0002 respectively). Alcoholic patients with Child-Pugh A/B were more susceptible to infection compared to nonalcoholic patients ( p = 0.02), although no difference was noted as to the number of deaths ( p = 0.1). With regard to patients with Child-Pugh C, no statistical difference was found in the infections or deaths among alcoholics and nonalcoholics ( p = 0.8, p = 0.8). CONCLUSIONS: Our findings suggest that, despite the fact that bacterial infections are more common in cirrhotic alcoholics, its seems that the mortality rate is associated more with the severity than with the etiology of the hepatic disease.

Intestinal permeability in liver cirrhosis.

To determine the changes in intestinal permeability in liver cirrhosis and to investigate whether intestinal permeability relates to the stage and aetiology of cirrhosis or existence of spontaneous bacterial peritonitis (SBP). A prospective study of intestinal permeability in patients with cirrhosis. Gastroenterology and Nuclear Medicine Departments of Ege University Hospital. Intestinal permeability was assessed in 44 consecutive patients with cirrhosis and 10 healthy volunteers by measuring 24 h urine excretion of (99m)technetium diethyl triamine penta-acetic acid (99mTc DTPA). Cases with an associated disease, impaired renal function, continuing alcohol consumption and drug intake which is known to have an effect on intestinal permeability were excluded. Comparisons of 24 h urine excretion of 99mTc DTPA were made between the groups of cirrhotics and controls, different grades of cirrhosis (according to Child-Pugh criteria), alcoholic and non-alcoholic cirrhotics and cirrhotic patients with and without SBP. Patients with cirrhosis excreted 99mTc DTPA significantly more than controls (11.56 +/- 8.96% in cirrhotics and 4.30 +/- 1.49% in controls, P < 0.0001). There was no relationship of 24 h urine excretion of the tracer with the grade and aetiology of cirrhosis (12.20 +/- 9.47%, 11.41 +/- 9.84%, and 11.09 +/- 8.42%, in Child A, B, and C groups and 8.45 +/- 6.57% and 12.05 +/- 9.25% in alcoholic and non-alcoholic cirrhotics, respectively). No significant difference was found between cirrhotic patients with and without SBP in terms of excretion of the administered dose of 99mTc DTPA (9.98 +/- 9.47% and 12.20 +/- 8.82%, respectively). This study shows that intestinal permeability increased in cirrhotic patients regardless of the grade and aetiology of disease. The presence of SBP does not seem to be due to increased intestinal permeability.

N-Acetyltransferase-2, Glutathione S-Transferase M1, Alcohol Dehydrogenase, and Cytochrome P450IIE1 Genotypes in Alcoholic Liver Cirrhosis: A Case?Control Study

Background: Only a small percentage of long-term alcoholics develop liver cirrhosis. Genetic and non-genetic factors have been implicated in the risk of developing this disease. Among the genetic factors, case?control studies suggest an association with some polymorphisms at the alcohol dehydrogenase and cytochrome P450IIE1 genes. N-Acetyltransferase-2 metabolizes multiple compounds, transforming some of them to organ-toxic compounds and others into non-toxic molecules. Slow- and rapid-acetylator individuals exist in most human populations, and the mutations responsible for the slow-acetylator genotype have been determined. Slow acetylators, who should be at higher risk of developing breast cancer, and fast acetylators, who have an increased risk of developing colon cancer, can be characterized by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) genotyping. GSTM1 is another detoxifying enzyme for which functional interindividual differences, on the basis of gene polymorphisms, have been described. Methods: We conducted a case-control study in which 120 alcoholic cirrhotics, 30 long-term non-cirrhotic alcoholics, and 200 healthy controls were genotyped for polymorphisms (RFLPs) at the ADH2, P450IIE1, and NAT2 genes. PCR, followed by restriction enzyme digestion, was performed. The homozygous deletion of the GSTM1 gene was also PCR-analyzed. Genotype frequencies were statistically compared. Results: Frequencies for the ADH2, P450IIE1, and GSTM1 polymorphisms did not differ between patients and controls. Individuals homozygous for the NAT2*5 allele, which is the most frequent slow-acetylator (SA) allele and shows the lowest acetylator activity, were at a significantly decreased frequency among the cirrhotic patients compared with controls (9% versus 16%; P = 0.042). The frequency of this SA genotype was significantly increased (40%) in long-term alcoholics who did not develop cirrhosis (P = 0.0041 compared with controls; P = 0.000017 compared with cirrhotics). Conclusions: According to our results, NAT2 activity may be a factor that determines the risk of developing alcoholic liver cirrhosis, and slow acetylators would be protected.

Outcome of liver transplantation in critically ill patients with alcoholic cirrhosis: survival according to medical variables and sobriety.

At our center from August 1989 to December 1992, 834 adults underwent orthotopic liver transplantation (OLT) using tacrolimus as the primary immunosuppressive agent. A total of 183 adults (22%) had alcohol-related liver disease. Patients with alcoholic cirrhosis had a better though not statistically significant 5-year survival rate compared with all other patients. We were interested in specific predictors of survival, particularly for alcoholic cirrhotics who were gravely ill at the point of transplantation. For the 78 patients with alcohol-related liver disease who were United Network for Organ Sharing status IIA (critically ill) at the point of transplantation, variables of length of sobriety, alcohol rehabilitation, and medical variables (ventilator support, dialysis, vasopressor support, degree of encephalopathy, and infection) were assessed for contribution to survival. Although there was a trend toward poorer survival in patients with the shortest length of sobriety (< or =1 month), pre-OLT length of sobriety or alcohol rehabilitation did not predict survival. However, these patients tended to be in multiorgan failure and encephalopathic. Nevertheless, pre-OLT dialysis requirement was the only variable that predicted poorer survival (P < 0.002). This study was not designed to evaluate recidivism. However, we know that 24% of these patients have used alcohol at some point after OLT. Short pre-OLT length of sobriety may not predict which patients are likely to resume alcohol consumption after OLT, but it may identify patients in whom there will exist a variety of poor outcome variables. In our study, in these patients, post-OLT survival was associated with medical rather than alcohol history variables.

The Influence of Alcoholism and Cirrhosis on Benzodiazepine Receptor Function

In a previous study we reported that the affinity of the platelet benzodiazepine receptor was greater in alcoholic cirrhotic patients compared with normal controls and that there were detectable ligands for the neuronal benzodiazepine receptor in plasma from both alcoholic and nonalcoholic cirrhotic patients. The aim of the present study was to assess the separate contributions of alcoholism and cirrhosis to the presence of ligands in plasma for the neuronal and peripheral benzodiazepine receptors and to changes in peripheral benzodiazepine receptor binding in platelets. These parameters were measured in 10 alcoholic cirrhotics, 9 nonalcoholic cirrhotics, 7 alcoholics with a normal liver function, and 15 nonalcoholic subjects and normal liver function. Both groups of alcoholics had been abstinent for several months and the nonalcoholic groups had abstained for 24 h before the study. The concentration of ligands for the peripheral benzodiazepine receptor were significantly higher in both cirrhotic groups compared with the other two groups, suggesting that cirrhosis was responsible for this accumulation. Furthermore, the cirrhotic patients with detectable concentrations of these ligands had significantly poorer episodic memory than those without ligands. However, the presence of ligands for the peripheral benzodiazepine receptor did not correlate with the change in receptor affinity, which was increased in the alcoholic cirrhotic group compared with all other groups. Neither cirrhosis nor alcoholism altered the peripheral benzodiazepine receptor number. The cirrhotic patients with detectable ligands for the neuronal benzodiazepine receptor showed psychomotor slowing and executive dysfunction. The results suggest that the ligands for the peripheral benzodiazepine receptor may contribute to some of the cognitive deficits seen in hepatic encephalopathy, but are not responsible for the receptor affinity change seen in the alcoholic cirrhotics. This affinity change is not solely due to the effects of alcohol and could possibly serve as a marker for those at risk for developing alcoholic cirrhosis.

Erythrocyte membrane lipids and serum selenium in post-viral and alcoholic cirrhosis

Erythrocyte-membrane fatty acid composition and cholesterol content were evaluated along with serum selenium in 33 patients with liver cirrhosis and in 40 normal subjects. Thirteen patients were suffering from post-viral (group V) and 20 from alcoholic (group A) cirrhosis. The aim of the study was to elucidate whether membrane lipid abnormalities in cirrhosis were linked to the aetiology of the disease or whether they were the results of the cirrhotic process itself. The patients presented a significant increase in membrane cholesterol, palmitic acid (C16:0) and saturated fatty acids (SFA), and a decrease in polyunsaturated fatty acids (PUFA) and polyunsaturated/saturated fatty acids ratio (P/S) compared with the control group. Serum selenium levels were significantly reduced. When patients were subdivided according to aetiology, the alcoholic patients showed greater lipid composition abnormalities than the viral cirrhotics (higher levels of SFA and lower PUFA and P/S), while pathologic palmitic acid, membrane cholesterol and serum selenium values were confirmed in both groups of patients. In conclusion, low serum selenium and a series of erythrocyte membrane lipid composition abnormalities would appear to be features peculiar to cirrhosis. Alcoholic cirrhotics, on the other hand, show a more deranged erythrocyte membrane lipid profile.

New predictive factors for survival in abstaining alcoholic cirrhotics

New predictive factors for survival in abstaining alcoholic cirrhotics

Isokinetic Muscle Strength and Its Association with Neuropsychological Capacity in Cirrhotic Alcoholics

Alcoholic cirrhotics (n = 49), nonalcoholic cirrhotics (n = 42), and normal controls (n = 50) were compared on measures of isokinetic muscle strength and neuropsychological capacity. Alcoholic cirrhotics were deficient on measures of eccentric and concentric muscle movements, compared with normal controls but were not different from nonalcoholic cirrhotics. Nor were differences observed between the two cirrhotic groups on neuropsychological tests of cognitive and psychomotor capacity, suggesting that cirrhosis rather than alcoholism per se is responsible for the manifest deficits. Psychomotor capacity correlated negatively with isokinetic strength in cirrhotic subjects. These findings suggest that muscle weakness, due either directly to advanced liver disease or mediated by subclinical hepatic encephalopathy, accounts for a portion of the variance on the neuropsychological test performance of cirrhotic alcoholics.

Significance of liver size in hepatic surgery.

The purpose of this study was to evaluate the significance of liver volumetry as a parameter for hepatic functional reserve in cirrhotic patients with hepatocellular carcinoma. Liver volume was calculated from preoperative computed tomograms of 44 cirrhotic patients who underwent elective hepatic resections for hepatocellular carcinoma. The liver volume per body weight of non-alcoholic cirrhotics was significantly smaller than that of alcoholic cirrhotics (20.9 vs. 26.7 cc/kg; p=0.03). The values for alcoholic cirrhotics was comparable with normal values. The liver volume per body weight of the cirrhotic patients demonstrated correlation with the preoperative serum albumin (p<0.01) and indocyanine green clearance (p=0.02). We conclude that the determination of hepatic atrophy by volume try can serve as a parameter for the assessment of hepatic reserve but not as a predictor of postoperative complications in elective liver surgery for cirrhotic patients.

Zinc, copper, manganese, and iron in chronic alcoholic liver disease

Ethanol consumption and/or liver damage may alter liver content of several trace elements, as iron, zinc, copper, and manganese. This alteration may play a role on ongoing liver fibrogenesis. Based on these facts we have determined liver, serum, and urinary Mn, Cu, Zn, and Fe levels in a group of alcoholic cirrhotics and noncirrhotics with normal renal function, comparing them with those of controls. We have observed low liver zinc and high liver copper—this last in relation with histomorphometrically determined total amount of liver fibrosis—and manganese contents in cirrhotics, together with increased excretion of zinc and iron and decreased excretion of manganese. Zinc, iron, and copper excretion kept a relation with data of severity of cirrhosis, including mortality in the case of urinary copper, independently of the use of diuretics. Thus, liver copper and urinary iron, zinc, and copper excretion seem to be related with data of severity of chronic alcoholic liver disease. Low urinary manganese excretion may play a role on liver manganese overload.

Assessment and follow-up of alcohol-dependent liver transplantation patients a clinical cohort

We describe pretransplantation characteristics of 103 consecutive alcoholic cirrhotics who underwent orthotopic liver transplantation over a 28-month period, and follow-up characteristics for 58 of 82 survivors. We examined whether certain pretransplantation psychiatric and demographic variables predicted posttransplantation outcomes. Patients who were sober ⩽6 months and those who died after transplantation had longer transplant hospital stays, suggesting that physiological compromise may predict posttransplant course. Using survival analyses because of variable follow-up intervals, only age over 50 years and index hospital stays greater than 1 month showed statistical trends toward predicting shorter posttransplant survival duration. Neither pretransplant sobriety, gender, nor duration of pretransplant heavy drinking predicted posttransplant survival duration. No variable, including pre-operative sobriety ⩽6 months or attendance at alcohol rehabilitation peritransplant, predicted relapse except for female gender and pretransplant unemployment, in which cases the relapse rate was doubled. Our relapse rate of 21% is comparable to recidivism rates reported from other centers and for the general alcoholic population. These findings, several of which are contrary to general beliefs, continue to challenge our presumed predictive variables in selecting the best candidates for liver transplantation.

Cytochrome P4502E1 hydroxyethyl radical adducts as the major antigen in autoantibody formation among alcoholics

BACKGROUND & AIMS: We have previously reported that alcoholics have increased titers of immunoglobulins reacting with protein adducts of hydroxyethyl free radicals. Because hydroxyethyl radicals are produced during ethanol metabolism by liver microsomes, the aim of this study was to determine whether such antibodies recognize microsomal proteins complexed with hydroxyethyl radicals. METHODS: Liver microsomal proteins reacting with the anti-hydroxyethyl radical antibodies were characterized by an enzyme-linked immunosorbent assay and Western blotting. RESULTS: Alcoholic cirrhotics, but not patients with nonalcoholic cirrhosis or healthy subjects, had increased serum levels of immunoglobulin G and A directed against antigens produced in microsomes incubated with reduced nicotinamide adenine dinucleotide phosphate (NADPH) and ethanol. Such immunoreactivity was completely blocked when microsomes were incubated with ethanol in the presence of the spin-trapping agent 4-pyridyl-1-oxide-t-butyl nitrone or by preincubating the sera with hydroxyethyl radical-bound human albumin. Immunoblotting of proteins from human liver microsomes incubated with NADPH and ethanol showed that 86% of the sera from alcoholic cirrhotics reacted with a 52-kilodalton protein, whereas variable reactivity was observed with proteins of 78, 60, and 40 kilodaltons, respectively, The 52-kilodalton protein was identified by immunoblotting and immunoprecipitation as ethanol-inducible cytochrome P4502E1. CONCLUSIONS: Antibodies from alcoholic cirrhotics specifically recognized hydroxyethyl radical-cytochrome P4502E1 adducts, suggesting the possible implication of these antigens in the development of autoimmune reactions in alcoholic liver disease. (Gastroenterology 1996 Jul;111(1):206-16)