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.

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.

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.

EEG sleep studies in "pure" primary alcoholism during subacute withdrawal: relationships to normal controls, age, and other clinical variables.

Electroencephalogram (EEG) sleep recordings were compared in 34 normal controls and 31 inpatients with relatively pure primary alcoholism who had been abstinent for about 17 days. Compared with normal controls, primary alcoholics took longer to fall asleep, slept less, and had poor sleep efficiency. Sleep loss reflected reduced non-rapid eye movement (NREM) sleep, especially stage 2 sleep, stage 4 sleep, and total delta (stage 3 and 4) sleep. Alcoholic patients had higher REM density of the first REM period. Sleep deteriorated with age in both normal controls and patients, with younger alcoholics showing sleep patterns typical of older controls. Among other clinical-demographic variables examined, the shorter the duration of sobriety at the time of the study, the later patients went to bed and fell asleep. The number of drinks per drinking day in the 3 months before admission was directly related to the duration of the first REM period. In addition, the maximum number of withdrawal symptoms the patient had ever experienced was inversely related to the amount of delta sleep. Sleep measures were not correlated with depression rating, liver enzymes, or other measures of alcohol consumption.

The association between severity of DSM-III-R alcohol dependence and medical and social consequences.

This paper describes the relationship between severity of dependence and medical and social consequences in a clinical sample. Respondents constitute a sample of 219 men and 162 women interviewed in nine alcohol programs in a Northern California county. Results suggest that the number of dependence indicators reported by respondents is a valid indicator of severity of alcohol dependence, and that there is a positive relationship between the number of indicators and the number of medical and social consequences reported by respondents. When specific medical and social consequences are examined, an analysis restricted to men only, the number of dependence indicators is associated with stomach, heart and liver problems, DTs, hallucinations, public drunkenness, family arguments and serious accidents, but it is not associated with drunk driving arrests and job problems.

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.

The long-term course of treated alcoholism: II. Predictors and correlates of 10-year functioning and mortality.

This study examines factors related to mortality and 10-year posttreatment functioning for a sample of alcoholic patients who return to their families after an index residential treatment episode. Of the 113 patients followed 2 years after treatment, 20 had died by the time of the 10-year follow-up. Mortality risk was greater among patients who, prior to treatment, consumed more alcohol and were unemployed. Mortality was more strongly associated with medical conditions, liver problems, medication use and lack of confidants assessed 2 years posttreatment. The course for the surviving patients between the 2-year and 10-year follow-ups was one of improvement in terms of alcohol consumption, relative stability in terms of physical symptoms and depression, and an aging-related decline in social activities and employment. Life context and coping factors assessed 2 years after treatment were predictive of long-term outcome. Persons in less stressful life situations, in more cohesive and organized families, and who more frequently used active cognitive coping responses at the 2-year follow-up tended to function better at the 10-year follow-up. Overall, the findings support the value of embedding long-term follow-up studies in a theory of the disorder that is the target of the intervention.

Integrated outpatients treatment for medically ill alcoholic men: results from a quasi-experimental study.

OBJECTIVE: This report documents the findings of a quasi-experimental study of a new approach to treating medically ill alcoholics. The intervention, the Alcohol Related Disorders (ARD) Clinic, consists of concurrent alcohol treatment and medical care delivered by an interdisciplinary team in an outpatient medical clinic at the Minneapolis Veterans Affairs Medical Center (MVAMC). METHOD: We compared 50 ARD patients with 50 patients who met eligibility for the clinic, but had to be referred elsewhere because the clinic was full at the time (referred patients). Referred patients received medical care in other MVAMC clinics or in the community. RESULTS: During the 2-year follow-up period, ARD patients returned for outpatient visits over three times as often as referred patients (p < .001). More referred patients received no follow-up care at MVAMC (p < .01). ARD patients had more frequent (p < .05) but briefer (p < .01) hospitalizations. Almost twice as many referred (32%) as ARD patients (18%) died during the follow-up period. Referred patients ranged from 1.18 times less likely to 5.03 times more likely to die during follow-up than those in the ARD group (p = .11). ARD patients lived for an average of 82 days longer than referred patients, and each ARD clinic visit in the second follow-up year predicted an additional 3.5 days lived (p < .01). CONCLUSIONS: Integrated outpatient treatment for medically ill alcoholics appears to improve outpatients follow-up and alter patterns of hospitalization when compared with standard approaches. Two-year mortality may have been reduced as a result.

Liver function tests and neuropsychologic impairment in substance abusers.

The relationship between residual neuropsychologic dysfunction in alcoholics and subtle changes in liver function during acute phases of treatment was examined. Noncirrhotic alcoholics who exhibited extreme elevations in the liver enzyme gamma-glutamyl transferase (GGT) were found to have greater impairments in tasks of visuoperceptual and conceptual abilities when compared to alcoholics with normal or only mild elevations in GGT. The relationship between acute liver dysfunction and residual neuropsychologic impairment appeared to be independent of age and patterns of drinking. The implications of these findings in relation to treatment planning and prognosis of alcoholics are discussed.

Recent developments in alcoholism:the liver.

The past decade has witnessed major gains in our understanding of the pathogenesis and therapy of alcoholic liver disease. The molecular biology of alcohol-metabolizing enzymes is well understood. Older concepts of liver injury, e.g., hypermetabolism, generation of free radicals, mitochondrial and microtubular dysfunction, and impairment of liver regeneration by ethanol, have been studied in greater detail. The fibrotic response to alcoholic liver injury has been explored, revealing complex interrelationships between the nonparenchymal cells of the liver and showing the importance of cytokines in regulating these cells. New mechanisms of injury have been appreciated, most prominently the association between hepatitis C infection and alcoholic liver disease, and the formation of protein-acetaldehyde adducts in the liver of alcohol-fed subjects. A new animal model of alcoholic liver injury, the alcohol infusion rat model developed by French and Tsukomoto, promises to provide a relatively simple model for researchers. The clinical management of alcoholic liver disease continues to evolve. Focal fatty change is recognized as a variant of alcoholic fatty liver. Nonalcoholic steatohepatitis has been described as a mimic of alcoholic liver disease, and may provide insight into the mechanisms of perivenular liver injury. The presence of perivenular fibrosis may predict at an early stage which patients are at risk for serious liver injury. Nutritional and corticosteroid therapy of alcoholic hepatitis are now established. Other therapies such as propylthiouracil, glucagon plus insulin infusion, and colchicine have been studied in large trials. Alcoholic liver disease can now be treated in selected cases by liver transplantation.

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.

Divergence of ethanol and acetaldehyde kinetics and of the disulfiram-alcohol reaction between subjects with and without alcoholic liver disease.

Despite standardization, marked interindividual variation in the severity of the disulfiram-alcohol reaction (DAR) has been observed. We studied the DAR in 51 consecutive alcoholics with (n = 16) and without (n = 35) significant alcoholic liver disease. Clinical signs of the DAR were much weaker in the patients with compared with those patients without liver disease. Because acetaldehyde is thought to be the main cause of the DAR, we studied ethanol and acetaldehyde kinetics in 13 patients (6 females, 7 males) with alcoholic liver disease (documented by biopsy, clinical and/or radiological findings, and by quantitative liver function) [galactose elimination capacity (GEC) 4.2 +/- SD 1.0 mg/min/kg; aminopyrine breath test (ABT) 0.14 +/- 0.10% dose x kg/mmol CO2] and 13 age- and sex-matched controls (alcoholics without significant liver disease, GEC 7.1 +/- 0.7; ABT 0.81 +/- 0.35). Clinical signs of acetaldehyde toxicity during the DAR (flush, nausea, tachycardia, and blood pressure drop) were absent in alcoholic liver disease, but clearly evident in controls. Blood ethanol kinetics were similar in both groups, Cmax and area under the concentration-time curve (AUC) being 6.27 +/- 1.82 and 368.9 +/- 72.9 mmol x min/liter in alcoholic liver disease, and 6.62 +/- 1.71 and 377.6 +/- 124.5 in controls, respectively. In contrast, there was a strong (p < 0.001) difference in Cmax and AUC of acetaldehyde, respective values being 33.46 +/- 21.52 and 1463.8 +/- 762.5 mumol x min/liter in alcoholic liver disease, and 110.87 +/- 56.00 and 4162.0 +/- 2424.6 in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized study of secondary prevention of early stage problem drinkers in primary health care.

The subjects were recruited from participants in a health examination of random samples of the adult population in Stockholm county. Those aged 18-64 years who admitted a high alcohol consumption (greater than 40 g 100% ethanol/day) among men and greater than 30 g among women) or had an elevated value of serum-gammaglutamyltransferase (GGT) (cut-off point 1.0 microkatal/l for men and 0.6 microkatal/l for women) or had certain other indications of a high alcohol consumption were included. More severe cases, and those with an elevated GGT due to reasons other than alcohol, were excluded. The remaining subjects, 70 men and 13 women, were allocated at random to either an intervention or a comparison group. An elevated GGT was the main inclusion criteria. The subjects in the comparison group were advised by the general practitioner to cut their alcohol consumption, while those in the intervention group made further visits to their general practitioner, who gave general support and used an elevated GGT as an indication of the recent level of alcohol consumption at consecutive visits. There were three visits on average, so we are comparing a group receiving advice with a group receiving further minimal intervention. At the one-year follow-up there were greater, however not significant, reduction in GGT-level, in self-reported alcohol consumption and in a 'problem index' in the minimal intervention group than in the comparison group.

Measurement of hemoglobin-acetaldehyde adduct in alcoholic patients.

A sensitive and specific test for chronic alcohol abuse is useful in the diagnosis and management of alcoholic patients. Herein, we report the measurement of hemoglobin-acetaldehyde adducts (Hb-AA) in alcoholic patients by a sandwich ELISA using different antibodies. Keyhole limpet hemocyanin (KLH), a peptide consists of eight amino acid residues (8-pep, V1 to K8) at the N-terminus of beta-chain of human sickle-cell Hb and a segment of HbA beta-chain consists of 11 amino acids rich in lysine or K (11-pep, G56-K66) were incubated with acetaldehyde and NaCNBH3 to form protein-AAs. 8-Pep-AA and 11-pep-AA were individually conjugated to unmodified KLH as the carrier. Anti-protein-AA IgGs were raised in rabbits using these three protein-AA immunogens. When anti-KLH-AA IgG was used in ELISA, optical densities for alcoholic patients and controls were 0.311 +/- 0.124 and 0.147 +/- 0.042 (means +/- SD, n = 40/group, p < 0.001), respectively. Using mean value +/- 2 SD of controls as the cut-off, sensitivities to detect alcoholic patients were 78, 75, and 43%, respectively, when anti-KLH-AA, anti-11-pep-AA, and anti-8-pep-AA were used. Correlation among optical densities obtained from the first two IgGs was excellent (R2 = 0.905). We conclude that: (1) Hb-AA has the potential of being a good marker for alcohol abuse, and (2) the site of Hb that is modified by acetaldehyde in vivo is primarily located in a surface-accessible domain near the center of the beta-chain of HbA where several lysine residues are clustered.

Occupational risk factors in patients with alcoholic or non-alcoholic liver disease.

The present study examines the presence of specific occupational risk factors in a group of patients suffering from alcoholic liver disease compared with a group of patients with non-alcoholic liver disease. The first group was more dependent on alcohol, with fewer social or psychological alcohol-related problems. The majority of them were employed, although more likely to be employed in traditional 'high risk' occupations. They showed lower job satisfaction, and the total sum of all previously reported occupational risk factors was highly significant. This was the first empirical evidence in support of the importance of the specific occupational risk factors previously postulated.

Clinical predictors of alcohol withdrawal delirium.

Up to now, clinical predictors for the course of the alcohol withdrawal syndrome, especially for the occurrence of a delirium, are lacking. Thus, this study was undertaken to examine whether clinical routine investigations at admission before the withdrawal syndrome can reveal factors indicating a higher risk for the development of a delirium. Our results showed that decreased serum electrolyte concentrations (i.e., chloride and potassium), elevated ALT, and gamma-glutamyltransferase serum levels, as well as ataxia and polyneuropathy at the neurological examination, indicate a higher risk for the development of an alcohol withdrawal delirium.

Mitochondrial function reflected by the decarboxylation of [13C]ketoisocaproate is impaired in alcoholics.

Mitochondria of patients with alcoholic liver disease exhibit structural abnormalities, and mitochondria isolated from animals exposed to ethanol are functionally deficient when studied in vitro. To assess possible functional consequences of these ethanol-associated alterations in vivo, we measured mitochondrial function in alcoholics noninvasively with a breath test. A mitochondrial function, the decarboxylation of ketoisocaproate (KICA), was assessed by measuring the exhalation of 13CO2 following the administration of 1 mg/kg 2-keto[1-13C]isocaproic acid, the decarboxylation of which occurs in mitochondria. The results of the KICA breath test in 12 alcoholic subjects were compared with the results in healthy controls and patients with nonalcoholic liver disease. The peak exhalation of 13CO2 and the fraction of the administered dose decarboxylated in 120 min were both significantly lower in alcoholics than in healthy controls and patients with nonalcoholic liver disease. In alcoholics, KICA decarboxylation was impaired in the presence of normal quantitative liver function tests such as the aminopyrine breath test and galactose elimination capacity, indicating that KICA decarboxylation does not simply reflect a decreased functional hepatic mass. The enrichment of circulating KICA with [13C]KICA was similar in alcoholics and controls, indicating that a decreased bioavailability or an increased dilution of labeled KICA cannot account for the decreased exhalation of 13CO2. It is concluded that mitochondrial function as reflected by KICA decarboxylation is impaired in chronic alcoholics. The functional impairment is specific for ethanol abuse and not a reflection of decreased global hepatic function. KICA decarboxylation could thus be useful as a marker for excessive ethanol consumption.