Alcoholic liver disease. Treatment strategies for the potentially reversible stages

Even modest alcohol ingestion can increase the risk of steatosis, and long-term, excessive consumption can lead to alcoholic hepatitis and eventually cirrhosis. Most patients with clinically significant alcoholic liver disease have histologic findings typical of all three conditions. The only clearly beneficial treatment is abstinence from alcohol. Abstinence in combination with proper nutrition and general supportive care is state of the art. Steatosis is reversible upon withdrawal of alcohol, but alcoholic hepatitis can persist even with abstinence and may progress to cirrhosis. Corticosteroid therapy may reduce short-term mortality rates in patients with moderate or severe alcoholic hepatitis who have hepatic encephalopathy but no evidence of infection or gastrointestinal bleeding. Treatment with colchicine may decrease the risk of cirrhosis; however, once cirrhosis has developed, the liver damage is irreversible. The prognosis is improved with abstinence, but complications (e.g., ascites, gastrointestinal bleeding) often occur. Liver transplantation may be considered in patients with severe complications.     

Medical treatment for alcoholic liver disease

The most effective treatment for alcoholic liver disease is abstinence from alcohol and it is the only treatment for patients with alcoholic fatty liver. Although many empirical therapeutic agents have been studied in the short-term and long-term treatment of alcoholic hepatitis, results have been mainly inconclusive. To date, only corticosteroids have proved to decrease the short-term mortality rate of patients with severe forms of acute alcoholic hepatitis. Corticosteroids are not beneficial to the majority of patients with mild or moderate forms of acute alcoholic hepatitis; such patients improve with abstinence from alcohol and general supportive measures and do not need a specific short-term treatment. Most long-term trials have only showed that most patients with alcoholic liver disease were neither abstinent nor compliant, and that long-term survival was strongly correlated to abstinence from alcohol. In one study, propylthiouracil decreased the long-term mortality rate of compliant patients with severe alcoholic liver disease who reduced their alcohol intake; however, further clinical trials are needed before propylthiouracil can be recommended. In another study, colchicine decreased the long-term mortality rate of cirrhotic patients, 45% of whom had alcoholic cirrhosis. Results were highly significant, and the need for further clinical trials of colchicine in the long-term treatment of alcoholic and non-alcoholic cirrhosis is imperative. Enteral nutrition should also be studied in severely malnourished cirrhotic patients, since it was shown to decrease the short-term mortality rate of such patients in a recent study.     

A model to examine the validity of the 6-month abstinence criterion for liver transplantation

Six months of abstinence from alcohol is a commonly used criterion for liver transplantation eligibility for patients with alcoholic cirrhosis. There is limited evidence to document the validity of this criterion with regard to risk of alcoholism relapse. Ninety-one patients with alcoholic cirrhosis were interviewed for relapse risk using the High Risk Alcoholism Relapse (HRAR) Scale. The HRAR model can be used to predict relapse risk independent of duration of sobriety and therefore can be used to examine the validity of the 6 months of abstinence criteria in this clinical population. The two methods demonstrated poor to fair agreement. Agreement was highest with a cutoff allowing a 5% 6-month relapse risk when 79% agreement (c = 0.56) was demonstrated between the two methods. Using the 6-month abstinence criterion alone disallows a significant number of candidates who have a low relapse risk based on their HRAR score. The validity of the 6-month abstinence criterion is supported somewhat by comparison with the HRAR model. However, use of the 6-month abstinence criterion alone forces a significant number of patients with a low relapse risk by HRAR to wait for transplant listing. A relapse risk model based on an estimate of alcoholism severity in addition to duration of sobriety may more accurately select patients who are most likely to benefit from liver transplantation.     

Alcoholism: independent predictor of survival in patients with head and neck cancer

BACKGROUND: Despite recognition of the high prevalence of alcoholism among patients with head and neck cancer, the prognostic importance of alcoholism has not been evaluated adequately. Previous investigators have speculated that alcoholic patients may have a poorer prognosis than nonalcoholic patients because of more advanced stage of cancer, the immunosuppressive effects of alcohol, and an increased rate of death due to other alcohol-related diseases. PURPOSE: The goal of this population-based study was to identify the features of alcoholism that are associated with survival for patients with head and neck cancer and to develop an alcoholic severity staging system from a composite of the independent features of alcoholism. METHODS: This prospective study included 649 patients who were diagnosed with cancer of the oral cavity, oropharynx, hypopharynx, or larynx during the period from September 1, 1983, through February 28, 1987, in a three-county area of western Washington state that participates in the Surveillance, Epidemiology, and End Results Program of the U.S. National Cancer Institute. Details on lifetime alcohol consumption, treatment for alcoholism, abstinence from alcohol prior to the diagnosis of cancer, and alcohol-related health problems were ascertained through in-person interviews near the time of diagnosis. Patients were classified as either nonalcoholics or alcoholics according to their responses to questions from the Michigan Alcoholism Screening Test. The measures of alcohol consumption and abuse that were found to be independently associated with 5-year survival by logistic regression analysis were combined using conjunctive consolidation to create a final composite variable, called an alcoholic severity stage. Cox proportional hazards regression analysis was done to estimate the relative risk (R) of death within 5 years due to specific causes of death for each of the alcoholic severity stages. RESULTS: Alcoholism (RR = 2.06; 95% confidence interval [CI] = 1.43-2.98) and a history of alcohol-related systemic health problems (i.e., liver disease, pancreatitis, delirium tremens, or seizures) (RR = 2.76; 95% CI = 1.69-4.49) were associated with an increased risk of death, whereas abstinence (i.e., the consumption of fewer than one drink per week at 1 year prior to the diagnosis of cancer) (RR = 0.62; 95% CI = 0.39-0.97) was associated with a decreased risk of death. These associations were independent of age, site of cancer, anatomical stage, histopathologic grade, smoking, and type of antineoplastic treatment. Patients in the two worst alcoholic severity stages had an increased risk of dying not only of head and neck cancer but also of cardiovascular disease, pulmonary disease, and other alcohol-related causes. CONCLUSIONS: Alcohol abuse, measured by alcohol consumption, functional impairment, a history of alcohol-related health problems, or abstinence, can provide important prognostic information for patients with head and neck cancer. Our results suggest that sobriety among alcoholic patients can lead to prolonged survival.     

Effects of transdermal nitroglycerin on impedance to flow in the uterine, umbilical, and fetal middle cerebral arteries in pregnancies complicated by preeclampsia and intrauterine growth retardation

BACKGROUND: Uncertainty exists about the extent and consequences of a return to alcohol consumption after liver transplantation for alcoholic liver disease (ALD). AIMS: To determine the prevalence and consequences of alcohol consumption in patients transplanted for ALD. METHODS: A retrospective case controlled study of all patients transplanted for ALD at the Queen Elizabeth Hospital, Birmingham, between 1987 and 1996. RESULTS: Seventy patients with ALD were transplanted, of which 59 survived more than three months; 56 were interviewed. Twenty eight had consumed some alcohol after transplantation; for the nine "heavy drinkers" (HD), the median time to resumption of alcohol intake was six months and for the 19 "moderate drinkers" (MD) it was eight months. There was no significant difference in episodes of acute rejection or compliance with medication between those who were abstinent, MD, or HD. Histological evidence of liver injury was common in ALD patients who had returned to drink. Mild fatty change was found in 1/11 biopsy specimens from abstinent patients but moderate to severe fatty change and ballooned hepatocytes were seen in 3/5 MD and 2/5 HD specimens. Two HD patients had early fibrosis. One HD patient had died of alcohol related complications. CONCLUSIONS: Moderate to heavy alcohol consumption occurs in patients transplanted for ALD. Patient recall of abstinence advice is unreliable, and patients return to alcohol mainly within the first year after liver transplantation. Return to alcohol consumption after liver transplantation is associated with rapid development of histological liver injury including fibrosis.     

The disease controversy and psychotherapy with alcoholics

This article discusses conducting psychotherapy with alcoholics in light of the controversy about whether alcoholism is a disease. The belief that alcoholism is a disease forces many clinicians to offer abstinence from alcohol as the only option for alcoholics who seek treatment. From this perspective, the alcoholic must be helped to accept the idea that he or she has a disease and that to recover from this problem, drinking must stop. Others maintain that alcoholism may not be a disease and view alcoholic drinking as maladaptive behavior. From this vantage point, helping the patient to control or to moderate drinking might be considered. These two distinct paradigms lead to divergent treatment goals, which leaves the clinician in a quandary about how best to treat an individual who experiences a drinking problem. To resolve this dilemma, it is suggested that the clinician who works with alcoholics entertain a multiplicity of perspectives and should not be blinded by any one paradigm. While control of alcohol intake must take place if such patients are to improve their functioning, the author argues that recovery can occur either by abstinence or through moderating drinking.     

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

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

Older adult controlled drinkers and abstainers

Little is known about the lifetime course of alcohol problems, especially during late adulthood. Many individuals with a history of alcohol problems achieve remission of their symptoms through abstinence or controlled drinking. This study examined 135 older adults with a prior history of alcohol diagnoses who were symptom free for at least the past year. Two groups were identified based on their alcohol consumption within the past year: abstinent individuals (n = 92) and controlled drinkers (n = 43). The groups did not differ in age, racial composition, education, income, or years since their last alcohol-related symptom, but they did differ in gender composition, indices of alcoholism severity, history of formal and informal treatment, as well as lifetime alcohol consumption patterns. Abstinent individuals had more severe alcohol problems, consumed higher amounts of alcohol on drinking days, had more years of heavy alcohol consumption, and were more likely to have attended alcohol treatment and Alcoholics Anonymous (AA). The controlled drinkers had a longer history of moderate social drinking, and their current consumption habits appeared to be similar to symptom-free older adult drinkers. The results suggest that gender, alcoholism severity, history of formal and informal treatment, and past consumption patterns are associated with whether older adults with histories of alcoholism attain successful outcomes through abstinence or controlled drinking.     

Hormonal (ACTH, cortisol, beta-endorphin, and met-enkephalin) and cardiovascular responses to hyperthermic stress in chronic alcoholics

Chronic alcohol drinking causes profound alterations in hypothalamic-pituitary function. In the present study, endocrine [corticotropin (ACTH), beta-endorphin, cortisol, and met-enkephalin] and cardiovascular (blood pressure) changes in response to hyperthermic stress (sauna at 90 degrees C for 30 min) were evaluated in 25 normal men (25 to 50 years old) and in 48 male alcoholic subjects (34 to 56 years old) after 5 weeks of abstinence. Significantly lower increments in systolic blood pressure were observed in alcoholics than in control subjects. Furthermore, alcoholics showed lower ACTH, beta-endorphin, and cortisol increments in response to sauna than normal controls. In contrast, sauna-induced hyperthermia did not change significantly the circulating met-enkephalin levels in either normal controls or chronic alcoholics. These data suggest that an impairment in the adaptive response to stress affects alcoholic men even after a few weeks of abstinence from alcohol.     

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

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

Alcohol use following liver transplantation for alcoholic cirrhosis

Due to the significant increase in the number of patients with alcoholic liver cirrhosis being referred for liver transplantation, studies to determine recidivism rates and influential factors affecting those rates have become increasingly crucial. Between 12/85 and 12/91, 67 patients diagnosed with alcohol related end-stage liver disease underwent orthotopic liver transplantation at Baylor University Medical Center. A 3-8 year follow-up study was conducted wherein surviving patients were contacted by phone to evaluate subsequent alcohol consumption following transplantation (with the exception of two patients whose primary physicians were contacted). Of the 67 patients transplanted, 18 had expired, 7 were alive but unavailable, and 1 had been lost to follow-up. Of the remaining 41 patients interviewed, 21 had remained abstinent, while the other 20 had returned to some form of drinking. Of patients with less than 6 months of pretransplant abstinence, only 30% remained abstinent, while the other 70% had resumed drinking. Regarding patients with at least 6 months of pretransplant abstinence, 58% had remained abstinent, while the other 42% had resumed drinking. In both groups, nearly 1/3 of those who had admitted to posttransplant drinking reported themselves as again abstinent and recommitted to sobriety when interviewed. In conclusion, 49% of patients interviewed had resumed some type of drinking following transplantation-- however, this appears not to have affected compliance or survival potential. Only 2 (4.8%) of the 41 patients interviewed had returned to excessive drinking. Thus, our findings support the use of orthotopic liver transplantation for patients with alcohol related end-stage liver disease.     

Liver biopsy in ambulatory patients. Diagnostic value in comparison to conventional and quantitative liver function tests

In this retrospective analysis we investigated the diagnostic yield of 148 consecutive liver biopsies performed as an outpatient procedure. In 144 patients, adequate specimens for histologic analysis were obtained. In these patients, 226 diagnoses were entertained. Clinical diagnosis was confirmed in 49.3%, modified in 43.8% and altered in 6.9%. Liver biopsy was particularly helpful in patients where an alcoholic etiology was suspected, since this could be confirmed in only 59.4% while in the others different, often treatable, causes of chronic liver disease were found. Neither conventional nor quantitative liver tests (galactose elimination capacity, aminopyrine breath test) served to differentiate reliably between severe and mild lesions. We conclude that liver biopsy remains an important diagnostic tool in patients with chronic liver disease, and that it can be safely performed on an outpatient basis in appropriately selected patients.     

Abstinence or controlled drinking goals for problem drinkers: A randomized clinical trial.

24 adult problem drinkers were assigned to brief behavioral treatment with either an abstinence (AB) or a controlled drinking (CD) goal. Self-report and collateral report data reflect significant overall reduction in alcohol consumption and projected blood alcohol peaks at 3-mo and at 3.5-yr follow-up intervals. AB and CD Ss did not differ significantly from each other on outcome variables at any point before or after treatment. At 3.5 yrs, 4 Ss had been abstinent for at least 12 mo, 3 had been moderate and asymptomatic drinkers for at least 12 mo, 5 were improved but still somewhat impaired, 8 were unimproved, 3 refused to be interviewed, and 1 could not be located. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relation between the quantity, type and duration of alcohol drinking and the development of alcoholic liver cirrhosis

Patients with alcoholic liver cirrhosis in Dalmatian region are presented in this paper and their social and medical characteristics are reviewed. The alcohol drinking habits of 211 patients with established clinical-laboratory criteria of alcoholic liver cirrhosis were investigated. The obtained results have been compared with the results of the control group. The average age of the patients was 51.6 years. Males were more numerous (2/3 of all examinees), while the average duration of alcohol consumption was 25.4 years. Wine was the most frequently consumed beverage (about 90% of cases) and the average daily intake was 151 g of pure alcohol. The authors prove by mathematical model that the occurrence of liver cirrhosis increases exponentially with the increase of the amount of alcohol consumed. Relative risk of the development of alcoholic liver cirrhosis increases many fold with the increase of the amount of alcohol consumed.     

Experimental, clinical, and metabolic results of side-to-side portacaval shunt for intractable cirrhotic ascites

BACKGROUND: Intractable ascites, refractory to medical therapy, occurs in approximately 10 percent of patients with ascites from cirrhosis and is almost always fatal. Sinusoidal hypertension resulting from hepatic venous outflow obstruction plays a primary role in the pathogenesis of cirrhotic ascites and provides the rationale for decompression of the liver by side-to-side portacaval shunt in treatment of intractable ascites. This report presents the experimental basis for the use of side-to-side shunt and long-term results of a prospective study in 34 selected patients with intractable cirrhotic ascites. STUDY DESIGN: In the experimental studies, hepatic venous outflow obstruction and massive ascites were produced in dogs by ligation of the hepatic veins, and the effect of portacaval shunts on ascites, thoracic duct lymph flow, and aldosterone secretion were measured. In the clinical study, 34 carefully selected patients with cirrhosis (91 percent alcoholic) and truly intractable ascites (failure of medical therapy for 5 to 24 months) underwent side-to-side portacaval shunt. The effects on ascites, survival, metabolic abnormalities, and quality of life were studied prospectively during follow-up that was longer than 5 years in all but two patients. Quantitative Child's risk classes in percent of patients were A in 0, B in 68, and C in 32. RESULTS: In the experimental studies, side-to-side portacaval shunt permanently relieved severe ascites, reduced the 13-fold increase in thoracic duct lymph flow rate to almost normal, and abolished the aldosterone hypersecretory response to minimal hepatic venous outflow obstruction. End-to-side portacaval shunt was much less effective. In the clinical study, side-to-side portacaval shunt reduced mean portal vein-inferior vena cava pressure gradient from 282 mm saline to 4 mm and permanently relieved all patients of ascites without subsequent requirement of diuretic therapy. Two patients who died of hepatoma, and one who died of heart failure developed terminal ascites. Thirty-day mortality rate was 6 percent, and long-term survival rates at 5, 10, and 15 years were 75 percent, 74 percent, and 73 percent. In metabolic studies, side-to-side shunt produced marked diuresis and natriuresis and abolished hypersecretion of aldosterone. Quality of life was generally improved as a result of a low incidence of recurrent portal-systemic encephalopathy (6 percent), abstinence from alcohol in 91 percent, improvement in liver function in 81 percent, and improvement in Child's risk class. The portacaval anastomosis remained permanently patent in every patient. CONCLUSIONS: Side-to-side portacaval shunt is very effective treatment of intractable ascites from cirrhosis. Our results are attributable to careful selection of patients, an organized system of care, and a program of rigorous, lifelong follow-up that emphasizes abstinence from alcohol and dietary protein restriction.     

Molecular biology of prostatic intraepithelial neoplasia

Alcoholic hepatitis is a precirrhotic lesion; it develops in only a minority of chronic alcohol abusers even after decades of abuse. The clinical spectrum of disease varies from asymptomatic hepatomegaly to florid hepatocellular failure with gastrointestinal bleeding and hepatic encephalopathy. Corresponding variation is observed both in morbidity and mortality. The majority of individuals with mild to moderate alcoholic hepatitis improve significantly following abstinence from alcohol and the provision of a diet sufficient to meet their nutritional requirements; their long-term outcome is determined largely by their ability to maintain abstinence from alcohol. Individuals with severe alcoholic hepatitis require intensive nutritional support and vigorous management of the complications of their liver injury; their outcome is generally poor. A small, carefully selected subgroup of these very sick patients may benefit, at least in the short-term, from treatment with corticosteroids; the place of orthotopic hepatic transplantation, in this patient group, is still the subject of debate. No other treatment modalities have been shown to confer benefit consistently. A number of new therapeutic approaches have been proposed and need to be explored.     

Comparison of serum beta-hexosaminidase isoenzyme B activity with serum carbohydrate-deficient transferrin and other markers of alcohol abuse

We have compared beta-hexosaminidase (beta-Hex) activity, carbohydrate-deficient transferrin (CDT), mean corpuscular volume (MCV), gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values in serum from male alcoholic patients with the corresponding values in moderate and non-drinking subjects. The total beta-Hex activity was 2.5 times higher in the alcoholics than in the moderate drinkers and this increase was mainly due to a 5-fold increase in the activity of the B-isoform of the enzyme. This was expressed as a percentage of the total beta-Hex activity and called 'beta-Hex B%'. Strong correlations were found between alcohol consumption (g/ day) and beta-Hex B% (r = 0.757, P < 0.001, n = 42), alcohol consumption and CDT (r = 0.671, P < 0.001, n = 42), and beta-Hex B% and CDT (r = 0.628, P < 0.001, n = 57). Serum beta-Hex B% had a sensitivity of 94% and a specificity of 91% in detecting alcoholic drinking of > 60 g/day. As a single marker of alcoholic drinking, it was markedly more sensitive than MCV and the liver enzymes GGT, AST and ALT, and slightly more sensitive than serum CDT (94 vs 83%). At the CDT cut-off level of 20 U/l, 17% of the moderate and non-drinkers would have been classified as alcoholic drinkers and 17% of the alcoholics would have been classified as moderate drinkers. Some of these misclassifications were eliminated if the beta-Hex B% results were taken into account. We suggest that serum beta-Hex B% can be a useful and inexpensive laboratory test for alcohol abuse.     

Alcoholic hepatitis

Alcoholic hepatitis is the precursor of cirrhosis. Susceptibility is independent of amount and duration of ethanol intake or of diet. Centrilobular hyalin, the key morphologic abnormality, sensitizes lymphocytes to secrete factors which may account (in part) for necrosis, liver cell destruction, increased collagen synthesis and development of cirrhosis. Diagnosis may be facilitated by detection of alcoholic hyalin antigen (AHAg) and antibody (AHAb) in serum of patients with alcoholic hepatitis. Treatment requires abstinence. Steroids have not reduced mortality rates. Measures to improve immunologic reactivity may be helpful. Persons unable to abstain should be enrolled in a surveillance group.     

Cue exposure in moderation drinking: A comparison with cognitive–behavior therapy.

To date, the published controlled trials on exposure to alcohol cues have had an abstinence treatment goal. A modification of cue exposure (CE) for moderation drinking, which incorporated priming doses of alcohol, could train participants to stop drinking after 2 to 3 drinks. This study examined the effects of modified CE within sessions, combined with directed homework practice. Nondependent problem drinkers who requested a moderation drinking goal were randomly allocated to modified CE or standard cognitive-behavior therapy (CBT) for alcohol abuse. Both interventions were delivered in 6 90-min group sessions. Eighty-one percent of eligible participants completed treatment and follow-up assessment. Over 6 months, CE produced significantly greater reductions than CBT in participants' reports of drinking frequency and consumption on each occasion. No pretreatment variables significantly predicted outcome. The modified CE procedure appears viable for nondependent drinkers who want to adopt a moderate drinking goal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evaluation of the efficacy of naltrexone in alcoholism by the determination of serum carbohydrate-deficient transferrin

Naltrexone (NTX) has been shown to be a useful drug for the treatment of alcohol dependence (AD). Carbohydrate-deficient transferrin (CDT) in serum is a new biologic marker of alcohol abuse. To evaluate the efficacy of NTX (50 mg/d) in AD, a group of 20 alcoholics with CDT > 20 U/l was studied using monthly laboratory tests (CDT, ESR, AST, ALT, GGT) and specific psychological testing (CAGE). After the second month statistically significant differences in CDT levels were found. By the end of the study, 13 patients (responders) had normalized their CDT levels. There was no correlation between CDT values and the other laboratory markers. The difference in routine laboratory markers between responders and non responders was not significant. NTX was well tolerated by all the patients and significant alcohol abstinence was achieved. CDT was demonstrated to be a effective marker for the evaluation of alcoholic abstinence during treatment with NTX. Superior results were obtained in comparison with the routine customary markers for AD.