Coping and rehabilitation in alcoholic liver disease patients after hepatic encephalopathy--in interaction with professionals and relatives.

AIMS AND OBJECTIVES: To identify and describe conditions that limit or support patients, with alcoholic liver disease after surviving alcohol-induced hepatic encephalopathy, ability to cope with current and potential physical and psychosocial problems--in interaction with professionals and relatives--and to recommend appropriate interventions. BACKGROUND: Alcoholic liver disease patients surviving alcohol-induced hepatic encephalopathy have significantly impaired quality of life. Internationally, there is a lack of knowledge about the conditions that affect alcoholic liver disease patients' coping and rehabilitation. DESIGN: A grounded theory study. METHODS: Semi-structured interviews, conducted with 11 alcoholic liver disease patients who were diagnosed with hepatic encephalopathy. The interview guide was inspired by Richard S. Lazarus's theory of stress and coping. RESULTS: The elements that support or limit alcoholic liver disease patients' ability to cope with physical and psychosocial problems in interaction with professionals and relatives were represented by the core category 'Struggle for preservation of identity as a significant individual'. It was characterised by three categories, which are interrelated and impact upon each other: 'Acknowledgement', 'Struggle to maintain control' and 'Achieving a sense of security'. CONCLUSION: Alcoholic liver disease patients experience a struggle to preserve their identity as a significant individual. It can be assumed that professionals and relatives in their interaction with, and support of, patients should focus on strengthening and preserving patients' identity in the form of acknowledgement, helping alcoholic liver disease patients maintain self-control and providing a safety net so patients feel a sense of security. RELEVANCE TO CLINICAL PRACTICE: It can be assumed that professionals should support alcoholic liver disease patients' appraisal of, and coping with, physical and psychosocial problems based on acknowledgment, understanding and a sympathetic attitude. Professionals should proactively approach patients when they withdraw. It may be useful for professionals to be aware of alcoholic liver disease patients' individual coping strategies and thereby their individual requirements for professional supportive intervention.

Hemochromatosis gene mutations, liver function tests and iron status in alcohol-dependent patients admitted for detoxification.

BACKGROUND: Screening of target populations for hemochromatosis (HFE) gene allele status has been recommended. Alcoholic liver disease may be associated with iron overload and there is evidence of excessive alcohol consumption among patients with hereditary hemochromatosis. This study determined the HFE gene allele status in alcohol-dependent patients and explored the associations between iron status, liver enzymes, and HFE status. METHODS: A total of 151 consecutive patients admitted for alcohol detoxification were tested for HFE mutations, iron status, and liver function tests. The prevalence data were compared with those from a New Zealand population. manova was used to compare liver function tests and iron status for subjects with different HFE mutations. RESULTS: Three compound heterozygotes, one homozygote for C282Y, and one homozygote for H63D were found among the 151 patients. For the remaining 146 patients, there was no difference in the distribution of heterozygote status by allele, compared to the general New Zealand population. No HFE mutation: general population 64.4%, alcohol-dependent patients 64.4%; H63D: general population 23.6%, alcohol-dependent patients 28.1%; C282Y: general population 11.9%, alcohol-dependent patients 7.5% (P = 0.20). There was no relationship between liver function tests or iron status and HFE mutation status among the study group. CONCLUSIONS: No evidence has been found in the present that HFE allele status prevalence is different from the general population or associated with different liver function or iron status among alcohol-dependent patients. The cause of altered iron status among alcohol-dependent patients does not appear to be related to HFE status.

Efficacy of 6-month pretransplant abstinence for patients with alcoholic liver disease undergoing living donor liver transplantation.

PURPOSE: Questions have been raised regarding the ethics of liver transplantation in patients with alcoholic liver disease (ALD), including the fairness of cadaveric organ allocation to individuals who abuse alcohol and the efficacy of transplantation in these patients, many of whom may relapse. Living donor liver transplantation (LDLT) for ALD patients raises the similar ethical issues. ALD candidates for cadaveric liver transplants are required to abstain from alcohol for 6 months before being listed, but the efficacy of 6 months of abstinence in ALD patients receiving LDLT is not known. METHODS: We therefore determined the efficacy of 6 months of pretransplant abstinence in 15 ALD patients who underwent LDLT from February 1997 to December 2003. RESULTS: The Model for End-stage Liver Disease score was 24 +/- 10, and mean pretransplant abstinence period was 15 +/- 13 months, with 11 (73.3%) patients being abstinent for at least 6 months. Four patients received dual grafts, making the number of living donors 19: 12 children, two wives, one brother, three nephews, and one aunt. There were no unrelated donors. Three patients showed a relapse to alcohol drinking. The overall 1-, 3-, and 5-year survival rates were 100%, 100%, and 87.5%, respectively, and the cumulative 1-, 3-, and 5-year relapse rates were 6.7%, 20%, and 20%, respectively. The relapse rates in patients who did and did not maintain 6 months of abstinence were 9.1% and 50%, respectively; this difference was not significant (P = .154), likely due to the small sample size. Younger recipient age was a significant risk factor for alcohol relapse (40 +/- 8 years versus 53 +/- 6 years; P = .004). CONCLUSIONS: Pretransplant abstinence of 6 months seemed to be beneficial. For ethical reasons, a 6-month abstinence rule should be strictly observed in LDLT.

A pilot study of an alcoholic liver disease recurrence prevention education program in hospitalized patients with advanced liver disease.

No systematic work has been completed to assess whether or not educational programming might exert lifestyle improvements among alcoholic liver disease (ALD) inpatients. The present pilot study sought to answer this question through the use of a small-scale two-group experiment (five-session education program versus standard care) at a state-of-the art Liver Unit that provided tertiary care of indigent patients with advanced ALD. A total of 44 patients were initially randomly assigned to program conditions, and 25 provided 3-month follow-up data (13 in the program condition, 12 in the control condition). Patients who received the program reported high receptivity to it, and showed greater learning of program material and reported greater lifestyle changes than the control patients. For those ALD inpatients that are able and willing to participate, the program shows promising effects on self-reported lifestyle change.

Low serum leptin levels and malnutrition in chronic alcohol misusers hospitalized by somatic complications.

AIMS: Leptin is a peptide produced by fat cells which regulates fat mass by decreasing food intake and increasing resting energy expenditure, so an increase of serum leptin could be an indicator of malnutrition. Our objective was to determine serum leptin levels (at admission and on the 15th day) in 79 male alcohol misusers, hospitalized by somatic complications, who drink more than 80 g ethanol/day, and to analyse its relationships with nutritional status assessed by anthropometry and dual-energy X-ray absortiometry (DEXA), insulin-like growth factor (IGF-1) and its binding protein (IGF1BP-3); acute phase reaction assessed by C-reactive protein (CRP), interleukin-6 (IL-6) and type II soluble receptor of tumour necrosis factor (TNF) (sTNFRII); serum oestradiol and testosterone; and the amount and duration of ethanol intake, the smoking habit and the presence of liver cirrhosis. METHODS: Patients were admitted through the emergency room, and blood for the above-mentioned determinations was taken at 08.00 on the following day, so none of the patients was acutely intoxicated at this time. The control group was composed of 32 healthy male (age-matched) subjects. RESULTS: Malnutrition was frequent among alcoholics. Serum leptin levels were closely related to total fat both in controls and in alcoholics. Serum leptin levels were decreased in alcoholics, even after adjusting for the amount of fat. Those alcoholics who reported anorexia and weight loss showed decreased leptin levels. After 15 days of hospitalization, serum leptin did not increase, in contrast with LDL cholesterol, serum albumin, prealbumin, IGF-1, IGF1BP-3 and testosterone which increased, whereas oestradiol and acute phase reactants, such as CRP, IL-6 and sTNFRII, were decreased. Serum leptin was not related to gonadal hormones at admission, but on day 15 we found a negative correlation between leptin and testosterone, and a positive one with oestradiol. CONCLUSIONS: Serum leptin levels are related to many factors, e.g. fat mass, age, smoking, serum testosterone and oestradiol levels, growth factors such as IGF-1 and CRP, and cytokines, such as IL-6 and sTNFRII. The most important of these is fat mass, as shown by multivariate analysis. Since serum leptin levels are decreased in alcohol misusers, we consider this decrease to be a consequence of a low fat mass.

Effect of maximal daily doses of acetaminophen on the liver of alcoholic patients: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Retrospective reports suggest that therapeutic doses of acetaminophen may be associated with fulminant hepatic failure and death in alcoholic patients. Millions of patients use acetaminophen; the prevalence of alcoholism in the United States is 5% to 10%. OBJECTIVE: To determine if hepatic injury was associated with maximal therapeutic dosing of acetaminophen to chronic alcohol abuse patients immediately following cessation of alcohol intake (the presumed time of maximal vulnerability). METHODS: Patients entering an alcohol detoxification center were enrolled in a randomized, double-blind, placebo-controlled trial. Exclusion criteria were baseline values of aspartate or alanine aminotransferase greater than 120 U/L, international normalized ratio greater than 1.5, serum acetaminophen level greater than 20 mg/L, or a history of ingesting more than 4 g/d of acetaminophen. Acetaminophen, 1000 mg, or placebo was administered orally 4 times daily for 2 consecutive days and liver test results were monitored for 2 more days. Acetaminophen was not administered until the alcohol had been eliminated. RESULTS: There were 102 patients in the acetaminophen-treated group and 99 patients in the placebo-treated (control) group. Demographic data, alcohol history, and baseline blood test results were similar in both groups. The mean (SD) aspartate aminotransferase level on day 4 was 38.0 +/- 26.7 U/L in the acetaminophen-treated group and 37.5 +/- 27.6 U/L in the placebo-treated group. There were 4 patients in the acetaminophen-treated group and 5 in the placebo-treated group who developed an increase in their serum aspartate aminotransferase level to greater than 120 U/L; it did not exceed 200 U/L in any patient. The mean (SD) international normalized ratio on day 4 was 0.96 +/- 0.09 in the acetaminophen-treated group and 0.98 +/- 0.11 in the placebo-treated group. CONCLUSION: Repeated administration of the maximum recommended daily doses of acetaminophen to long-term alcoholic patients was not associated with evidence of liver injury.

Hepatic and other medical disorders of alcoholism: from pathogenesis to treatment.

The medical risks of moderate and excessive alcohol consumption are reviewed. Current knowledge of metabolism of alcohol, including effects of moderate amounts, on hepatic metabolism and toxicity is summarized, with an evaluation of the relationship between the level of consumption and its effects on nutrients (including retinoids, carotenoids and folate), liver disease and other medical complications of alcoholism, including cardiovascular diseases and cancer. Putative benefits are also considered. Promising therapeutic approaches evolving from newly gained insight in the pathogenesis of medical complications of alcoholism are outlined.

High-performance liquid chromatography improves diagnostic efficiency of carbohydrate-deficient transferrin.

Carbohydrate-deficient transferrin (CDT) is considered a useful biochemical marker of regular high alcohol intake. CDT was measured in the sera of 51 alcohol abusers, 20 patients with non-alcoholic liver disease and 30 healthy controls with an alcohol intake of < 30 g/day. The mean CDT levels of these three groups respectively were determined with high-performance liquid chromatography (HPLC; 4.6 +/- 5.2%; 0.7 +/- 0.2%; 0.7 +/- 0.2%) and with a radioimmunoassay after microcolumn anion-exchange chromatography (MAEC/RIA; 34.2 +/- 26.9 U/l; 16.9 +/- 3.8 U/l; 18.0 +/- 5.7 U/l). CDT levels in patients with severe alcohol abuse (161.6 +/- 96.4 g/day) were significantly higher than in the two other groups under investigation (P < 0.0001). In heavily drinking subjects, the mean daily alcohol intake correlated with aspartate aminotransferase levels (ASAT) but not with the CDT levels determined either with HPLC or MAEC/RIA. With both methods, the CDT levels were slightly higher in patients with an ASAT concentration > 30 U/l, which may indicate an advanced liver damage (P < 0.05). Analysis of receiver-operating characteristic (ROC) plots demonstrated that the diagnostic accuracy of the HPLC method, which determines the relative amount of CDT, was significantly higher than the established MAEC/RIA method, which measures the absolute amount of CDT (area under the ROC curve: 0.95 +/- 0.02 vs 0.73 +/- 0.05; P < 0.0001). At a specificity of > 95%, the sensitivity of CDT determined with HPLC and MAEC/RIA was 80 and 47%, respectively. In addition, HPLC may be a useful and reliable method for the determination of this important biochemical marker, since the HPLC chromatogram is a visible document of the successful isotransferrin separation and measurement.

Two survival cases of alcoholic lactic acidosis complicated with diabetes mellitus and alcoholic liver disease.

We have experienced two patients with alcoholic lactic acidosis complicated with liver disease and diabetes mellitus who were successfully treated. They developed hypoglycemia, dehydration, lactic acidosis, and renal failure after drinking a large volume of alcohol without eating for 1 week before onset. Acidosis was thought to be directly related to excessive alcoholic intake, because it was no associated with severe liver failure and rhabdomyolysis. During monitoring of respiratory and circulatory functions, a rapid infusion of fluids adjusting to water and electrolyte imbalance was performed. A mixture of physiological saline and 5% glucose solution was thought to be effective in these cases. Patients recovered from renal failure and lactic acidosis without hemodialysis. Our experience will hopefully provide a key to successful treatment of fatal alcoholic lactic acidosis.

Liver transplantation for alcoholic liver disease.

UNLABELLED: Orthotopic liver transplantation (OLT) for individuals with alcoholic liver disease (ALD) remains controversial. This review was designed to evaluate the survival, recidivism, and rehabilitation of the alcoholic liver transplant recipient in a single transplant center. METHODS: Between 10/86 and 11/92 203 liver transplants were performed in 179 patients. In 42 patients (23%) the primary etiologic diagnosis was ALD (36 males, 6 females, median age 47 yr). All ALD patients were evaluated preoperatively by social service, psychiatry, and medical psychology, in addition to hepatology and transplant surgery. A minimum abstinence period of 3-6 months was encouraged, although exceptions were made for cases of extreme medical urgency in which a good prognosis for abstinence was predicted. RESULTS: In OLT recipients with ALD, actuarial survival at 1, 2, and 3 yr was 74%, 71%, and 71%, respectively, compared to 71%, 71%, and 69% for all OLT recipients. One- and two-year survival was 85% in the most recently transplanted 86 patients, 20 of whom (23%) had ALD with 1- and 2-yr survival of 84% (N.S.). Recidivism was monitored postoperatively by interviews with the patient and family, supplemented by random urine and serum toxicology. Of the 29 survivors, 2 (7%) returned temporarily to alcohol use but are presently abstinent. Although none of the ALD patients in this study was able to work prior to OLT, 76% of the survivors at least 4 months post-transplantation were employed. CONCLUSIONS: Although our experience is small, our results suggest that OLT is appropriate therapy for carefully selected patients with end-stage liver failure due to ALD. The multi-disciplinary approach to preoperative evaluation of the alcoholic liver transplant candidate is effective in determining those patients committed to abstinence after a successful transplant.

Sensitivity and specificity of carbohydrate-deficient transferrin as a marker of alcohol abuse are significantly influenced by alterations in serum transferrin: comparison of two methods.

Despite a number of investigations suggesting the value of carbohydrate-deficient transferrin (CDT) as a marker of alcohol abuse, a variety of issues on the applicability of CDT measurements in clinical settings have remained unexplored. Earlier studies in this field have focused on the relationship of CDT and the amount of alcohol consumption or presence of liver disease, whereas the influence of alterations in serum transferrin concentrations on CDT has received less attention. In this study, we compared two different methods for measuring CDT (CDTect and %CDT) and total transferrin concentrations in a sample of 83 alcohol abusers (20 patients with alcoholic liver disease and 63 heavy drinkers who were devoid of liver disease, despite excessive alcohol consumption) and 89 controls, who were social drinkers or abstainers. The control population included 53 hospitalized patients with expected abnormalities in serum transferrin concentrations caused by conditions such as negative iron balance, pregnancy, or nonalcoholic liver disease. Both methods gave significantly higher values in alcohol abusers than in controls (p < 0.01), but the overall sensitivity for detecting alcohol abuse was clearly higher for CDTect (59%) than for %CDT (34%). The correlation between the results obtained by the two methods (r = 0.629) significantly improved, when the CDTect values were replaced by the ratio of CDTect/total transferrin (r = 0.770) (p < 0.05). There was a positive correlation between the CDTect and serum transferrin (r = 0.201, p < 0.01), which was significant both in the alcoholics (r = 0.240, p < 0.05), and especially in the controls (r = 0.727, p < 0.001). A significant inverse correlation emerged between %CDT and total transferrin (r = -0.302, p < 0.01). The sensitivities of CDTect and %CDT for correctly classifying alcohol abusers in the subgroup of alcoholic liver disease patients were 90% and 70% and in the subgroup of heavy drinkers without liver disease (49% and 22%), respectively. Specificities for CDTect and %CDT in this sample were 81% and 100%, respectively. However, in the subgroup of hospitalized control patients with abnormal serum transferrin, the specificity of CDTect was only 48%. According to present data, CDTect seems to be more sensitive than %CDT for detecting alcohol abuse. However, any alteration in serum total transferrin concentration markedly decreases the assay specificity. This should be considered when interpreting the assay results in patients with elevated serum transferrin, such as iron deficiency, pregnancy, or liver diseases.

Alcohol dependence: is carbohydrate-deficient transferrin a marker for alcohol intake?

We investigated %CDT (carbohydrate-deficient transferrin) in 92 ethanol-intoxicated alcohol-dependent patients after consecutive admission to hospital and followed the for 28 days under controlled conditions. At admission, 63% (58 patients) showed elevated CDT (> 2.5%) and 34 patients (37%) had normal CDT levels (< 2.5%). No correlation of the %CDT values to alcohol-related disabilities, severity of the withdrawal syndrome, alcohol-drinking pattern before admission, or several other factors was found. The sensitivity of GGT (gamma-glutamyl transferase) was 58% for the same group of patients. Levels of %CDT decreased during the 28 days following abstinence, whereby we could separate four statistically different groups of "CDT decrease'. In two of these groups, comprising most of the cases studied, normal %CDT levels were reached after 14 days of abstinence. Those patients with %CDT levels exceeding the upper normal level after 14 days of sobriety, showed a decrease during the following 14 days to levels of 2.55-2.61%.

Erythropoietin and cytokine levels in the anemia of severe alcoholic liver disease.

PURPOSE: The anemia of chronic disease is mediated by the cytokines that modulate the immune response, such as tumor necrosis factor (TNF) and gamma-interferon (gamma-IFN), and is associated with a blunted serum erythropoietin (sEPO) response to anemia. Previous reports suggest that patients with liver disease (LD) also exhibit a blunted sEPO response to anemia, and that patients with alcoholic LD had altered cytokines, including elevated TNF levels. To investigate the pathogenesis of anemia in alcoholic LD, sEPO, TNF, and gamma-IFN levels were determined in patients who had participated in a Department of Veterans Affairs Cooperative study of alcoholic LD. METHODS: sEPO, serum TNF-alpha, and serum gamma-IFN levels were evaluated in 40 patients with severe biopsy-proven alcoholic LD whose serum had been stored during the Department of Veterans Affairs Cooperative Study 275, and in 18 patients with iron deficiency (controls). RESULTS: Mean hemoglobin (Hgb) was 11.2 +/- 0.3 g/dl for LD patients versus 11.4 +/- 0.4 g/dl for controls (p = 0.84). sEPO levels measured by ELISA were 29.6 +/- 4.1 units/liter in LD patients versus 25.4 +/- 5.4 units/liter in controls (p = 0.64). In both sets of patients, sEPO and Hgb were inversely related; the slopes of the two regression lines did not differ significantly (p = 0.92). TNF was detected in 3 of 40 LD patients and in 0 of 18 iron-deficient patients. Detection of TNF did not correlate with sEPO or Hgb, but did correlate strongly with severe caloric malnutrition (marasmus) and mortality at 6 months (p = 0.049 and 0.04, respectively). gamma-IFN was not detected. CONCLUSIONS: These findings indicate that the sEPO response is preserved in patients with severe alcoholic LD, and suggest that anemia in LD arises from different mechanisms than does the anemia of chronic disease. TNF production in severe alcoholic LD is strongly correlated with caloric malnutrition and mortality.

Acetaminophen metabolism in patients with different cytochrome P-4502E1 genotypes.

Cytochrome P-450 (CYP) 2E1 is the major ethanol-oxidizing enzyme of the nonalcohol dehydrogenase metabolic pathway in the liver. Recently, the presence of genetic polymorphisms of this enzyme was confirmed. In this study, to clarify the influence of CYP2E1 genotype on alcohol metabolism, we analyzed acetaminophen metabolism in subjects with different CYP2E1 genotypes. In normal subjects, a half-life of acetaminophen from blood was the longest in type A (c1/c1) and was the shortest in type C (c2/c2). The elimination rate in type C was more than twice that of type A and type B (c1/c2). In type A, both half-life and elimination rate of acetaminophen were not different between patients with noncirrhotic alcoholic liver disease within 1 week after abstinence and in normal subjects. In one patient with minimal change, there were no differences in both half-life and elimination rate within 1 and 6 weeks after abstinence. On the other hand, in type B, half-life was shorter and the elimination rate was greater in alcoholic noncirrhotic patients within 1 week after abstinence than in alcoholic patients with type A and in normal subjects with type B. In type B, half-lives were shorter, and the elimination rates were greater in patients with alcoholic liver disease within 1 week after abstinence than 4 to 6 weeks after abstinence. These results suggest the possibility that alcohol metabolism in individuals with the c2 gene may be greater than those with the c1 gene, and that the induction of CYP2E1 by ethanol in type B may occur more markedly than that in type A, although the sample number is too small to obtain final conclusions.