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Background

This worldwide problem affects everyone either directly or indirectly. Here are some statistics regarding the prevalence of the disease in the United States. Establishing the diagnosis frequently occurs all too late. It is estimated that 10% to 15% of alcoholics underreporting the quantity of alcohol they consume.

OUTLINE

Epidemiology  
Disease Associations  
Pathogenesis  
Gross Appearance and Clinical Variants  
Histopathological Features and Variants  
Laboratory/Radiologic/Other Diagnostic Testing  
Differential Diagnosis  
Prognosis and Treatment

 

Commonly Used Terms  
Internet Links  

 

EPIDEMIOLOGY CHARACTERIZATION
INCIDENCE  
Percentage of adult population with an alcohol problem 7%
Cause of death in urban areas 4th leading cause
Cirrhosis of the liver 9th leading cause
3.6 per 1000 persons
Acute and chronic pancreatitis 65% of cases

 

DISEASE ASSOCIATIONS CHARACTERIZATION
Nutritional Marasmus
Kwahiorkor
Pellagra
Scurvy
Endocrine Hypogonadism
Hyperestrogenism
Pseudo-Cushing's syndrome
Porphyria cutanea tarda
Infections Vibrio vulnificus sepsis
Acquired purpura fulminans
Pancreatitis Subcutaneous fat necrosis
Cullen/Grey Turner's sign
Connective tissue disease Dupuytren's contracture
Madelung's disease
Hematologic Coagulopathy
STROKE  

 

PATHOGENESIS CHARACTERIZATION
CARDIAC DAMAGE

Induction of both systolic and diastolic hypertension
Arrhythmias and alcoholic cardiomyopathy

Regional differences in peripheral circulation also occur with chronic alcohol use, with cutaneous vascular lesions most prominent on the upper body

The proposed mechanism for these changes is thought to be a direct action of alcohol on central vascular control mechanisms
I ncrease forearm blood flow and peripheral skin temperature in normal controls

Other vascular changes include an increased hemodynamic state, increased cardiac output, and decreased peripheral vascular resistance

Cellular immunity

Deficient in moderate as well as heavy drinkers because of a direct toxic effect of alcohol on the bone marrow

Acute as well as long-term alcohol use will reduce delayed-type hypersensitivity, whereas the number and function of T cells are reduced only in chronic drinkers

Number and function of granulocytes, including decreased chemotaxis and phagocytosis, is diminished

Adherence of neutrophils to the vascular endothelium is also impaired, although this is affected more by acute intoxication than long-term alcohol use

Humoral immune system is affected to a lesser degree than cellular immunity-heavy drinkers do experience a reduced primary antigen response to antibody production
Shorter half-life of immunoglobulins

Hemostasis

Inhibition of thrombocyte formation from megakaryocytes and decreased survival of platelets

Platelet aggregation is defective after acute, moderate, and heavy consumption of alcohol and is thought to be due to abnormal platelet membrane structure

Coagulation is also inhibited, with prolonged bleeding times seen at all levels of alcohol intake, likely secondary to a reduction in thromboplastin, which initiates the coagulation cascade

Abstinence from alcohol seems to reverse abnormal hemostasis, with bleeding time restored within 3 weeks

SKELETAL MUSCLE  

Evidence of apoptosis in chronic alcoholic skeletal myopathy.

Fernandez-Sola J, Nicolas JM, Fatjo F, Garcia G, Sacanella E, Estruch R, Tobias E, Badia E, Urbano-Marquez A.

Department of Medicine, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Spain.

Hum Pathol. 2003 Dec;34(12):1247-52 Abstract quote.  

Apoptosis is a common mechanism of programmed cell death that has been implicated in the pathogenesis of alcohol-induced organ damage. Experimental studies have suggested alcohol-mediated apoptosis in cardiac muscle. The relationship between skeletal and cardiac muscle damage in alcoholism led us to consider the possible role of apoptosis in the pathogenesis of skeletal myopathy.

We prospectively evaluated apoptosis in skeletal muscle biopsies of 30 consecutively selected male high-dose well-nourished chronic alcohol consumers and 12 nonalcoholic controls. Alcohol consumption, evaluation of muscle strength by myometry, and deltoid muscle biopsy with immunohistochemical and morphometric analysis were performed. Apoptosis was assessed by TUNEL, BAX, and BCL-2 immunohistochemical assays. Chronic alcoholics compared with controls showed a significantly higher apoptotic index in TUNEL (2.35% +/- 0.25% versus 0.18% +/- 0.03%, P < 0.001), BAX (9.16% +/- 2.00% versus 0.66% +/- 0.22%, P < 0.001), and BCL-2 muscle assays (8.08% +/- 0.20% versus 0.83% +/- 0.20%, P = 0.001), respectively. In addition, these apoptotic indexes were higher in alcoholics with skeletal myopathy compared with in those without skeletal myopathy (3.04% +/- 0.36% versus 1.65% +/- 0.26%, P = 0.004 for TUNEL; 17.00% +/- 2.78% versus 1.33% +/- 0.22%, P < 0.001 for BAX; and 15.13% +/- 3.2% versus 1.03% +/- 0.33%, P < 0.001 for BCL-2 assays, respectively).

We conclude that apoptosis is present in the skeletal muscle of high-dose alcohol consumers, mainly in those affected by myopathy. However, the specific pathogenic mechanism of apoptosis in chronic skeletal myopathy in alcoholics remains to be elucidated.

 

LABORATORY/
RADIOLOGY
CHARACTERIZATION
LABORATORY  
GENERAL  
CARBOHYDRATE-DEFICIENT TRANSFERRIN  
GGT  
HOMOCYSTEINE  
Raised plasma homocysteine levels in alcoholism: increasing the risk of heart disease and dementia?

Robinson G, Narasimhan S, Weatherall M, Beasley R.

Kenepuru Hospital, Porirua.
N Z Med J. 2005 Jun 3;118(1216):U1490. Abstract quote  

BACKGROUND: Raised plasma homocysteine levels, which may contribute to the increased risk of cardiovascular disease and dementia associated with alcoholism, have been observed in alcohol-dependent male subjects.

METHODS: In this study, we measured plasma homocysteine levels in 20 female and 31 male alcoholic subjects admitted to hospital for detoxification. Nutritional status and clinical factors that might predict plasma homocysteine levels were assessed by measurement of red cell folate, vitamin B12, blood alcohol, and liver function tests.

RESULTS: The median (interquartile range) plasma homocysteine level on admission was 15.4 micromol/L (11.1 to 19.7), with 27 (53%) subjects having a raised homocysteine level, greater than 15 micromol/L. There was no difference in admission plasma homocysteine levels between the male and female subjects (difference, male versus female 1.9 micromol/L, 95% CI=2.4 to 6.0, p=0.4). Red cell folate, vitamin B12 levels, and blood alcohol level on admission were not significant predictors of admission homocysteine level.

CONCLUSION: Severe alcohol dependence is associated with markedly raised plasma homocysteine levels in both females and males. The common condition of alcohol dependence may be an under-recognised risk factor contributing to raised plasma homocysteine levels and the associated risk of vascular and intellectual impairment.

 

GROSS APPEARANCE/
CLINICAL VARIANTS
CHARACTERIZATION
General  
VARIANTS  
SKIN  
Vascular
Spider telangiectasia
Palmar erythema
Corkscrew scleral vessels
Caput medusae
Flushing
Unilateral nevoid telangiectasia
Facial
Plethoric facies
Coloration
Jaundice
Hyperpigmentation
Other

Pruritis
Urticaria
Lichenoid dermatitis

Nails
Terry's nails
Red lunulae
Koilonychia
Clubbing
Skin cancer

Enhance the risk of squamous cell carcinoma (SCC) of the oral cavity in multiple studies

Cigarette smoking has a synergistic effect with alcohol on the development of oral SCC

Direct local effect of alcohol may play a role in oral carcinoma

A high correlation of alcohol consumption and upper digestive tract carcinoma has been reported, with a lack of correlation with other sites (eg, lung, bladder)-may be due to various cytotoxic or solvent properties of alcohol

Basal cell carcinoma (BCC) has been shown in most studies to have no greater incidence in patients with chronic alcoholism

However, other studies show an increased incidence of an infiltrative pattern of BCC in immunosuppressed patients, particularly those with chronic alcoholism. These tumors are more aggressive with a tendency toward local recurrence and destruction. Although the clinical appearance is similar to a nodular BCC, the histologic characteristics are unique

This subtype is characterized by an infiltrative pattern of invasion, poorly circumscribed growths of elongated tumor nests, loss of peripheral palisading, and minimal peritumoral inflammation

Int J Cancer 1988;42:825-8.
Am J Epidemiol 1990;131:597-611

Relationship between alcohol consumption and malignant melanoma (MM) is unclear. One study by Stryker, Stampfer, and Stein45 found total alcohol consumption to be a risk factor for MM. However, other studies have failed to find any correlation between drinking and MM.46-48

Oral
Black hairy tounge
Glossitis
Leukoplakia
Parotid swelling
Exacerbations of Skin Disease  

Psoriasis

 

Rosacea

 

Discoid eczema

 
CNS  

The frequency of brain lesions in alcoholics. Comparison between the 5-year periods 1975-1979 and 1983-1987.

Lindboe CF, Loberg EM.

Department of Pathology, Ulleval Hospital, Oslo, Norway.

J Neurol Sci 1988 Dec;88(1-3):107-13 Abstract quote

This is a follow-up study of a previous investigation of brain lesions in alcoholics during the 5-year period from 1975 through 1979 (Torvik et al. 1982).

The autopsy material from the 5-year period 1983-1987 was examined in order to see whether improved clinical treatment had resulted in a reduced frequency of alcohol-related brain lesions, particularly of active Wernicke's encephalopathy. The percentage of alcoholics (8.2 vs. 8.7%), the male/female ratio (4.2/1) and their mean age (60.4 vs. 62.2 years) were similar in the two recording periods, as was the frequency of alcoholic cerebellar atrophy (26.8 vs. 27.6%). In both periods the brain weight in male alcoholics aged 40-70 years was significantly lower than in age-matched controls. This difference was not present after 70 years of age. The most important finding was a considerable but not significant reduction of the frequency of active and inactive Wernicke's encephalopathy in alcoholics.

Review of the clinical records supports the hypothesis that this reduction reflects better diagnostic and therapeutic procedures in the clinical departments. However, even during the last period most cases of active Wernicke's encephalopathy were not recognized clinically and further improvement of the clinical management should therefore be possible.

Frontal lobe changes in alcoholism: a review of the literature.

Moselhy HF, Georgiou G, Kahn A.

Birmingham Addiction Research Group, Regional Addictive Behaviour Centre, Northern Birmingham Mental Health NHS Trust Headquarters, 71 Fentham Road, Erdington, Birmingham B23 6AL, UK.

Alcohol Alcohol 2001 Sep-Oct;36(5):357-68 Abstract quote

Alcohol can induce a wide spectrum of effects on the central nervous system. These effects can be recognized at the neurophysiological, morphological and neuropsychological levels. Several studies of the effect of alcohol on the frontal lobes were identified for review from MedLine, PsychLIT databases and by manual searching.

In this review article, the different changes are examined in detail. Computed tomography studies have reported changes of frontal lobe in alcoholism, while magnetic resonance imaging studies supported these findings. Neurophysiological studies with positron emission tomography and single photon emission computed tomography have reported a decreased frontal lobe glucose utilization and reduced cerebral blood flow. There is also evidence from neuropsychological studies that there are specific deficits in alcoholism that suggest frontal lobe dysfunction.

Considered together, these studies lend a strong credence to the concept of frontal lobe pathology in alcoholism. However, frontal lobe is not an isolated part of the brain and should be considered with its heavy connections to different cortical and subcortical areas of the brain.

HEART  

Alcohol and the heart.

Schoppet M, Maisch B.

Department of Internal Medicine, Cardiology and Angiology, Philipps University Marburg, Germany.

Herz 2001 Aug;26(5):345-52 Abstract quote

ALCOHOLISM IN GENERAL: Alcoholism is one of the major health problems in the world. Alcohol consumption has an impact on different body systems like the central nervous system, the gastrointestinal tract, the hematopoetic organs, and the cardiovascular system. Alcohol interferes with other medications, and drinking can exacerbate a variety of medical illnesses.

IMPACT ON THE HEART: In the heart, alcohol and its metabolite acetaldehyde confer a toxic effect on mitochondria as well as on the sarcoplasmatic reticulum, which is dependent on both the mean daily consumption and the duration of alcohol intake. A wide range of toxic effects of alcohol in distinct individuals can be observed and modest doses of alcohol can exert beneficial effects on the cardiovascular system probably by an increase in high density lipoprotein cholesterol (HDL) or changes in blood clotting mechanisms. Detrimental effects of alcohol on the heart comprise a decrease in myocardial contractility, hypertension, atrial and ventricular arrhythmias, and secondary non-ischemic dilated cardiomyopathy. After consuming large quantities of alcohol over years, alcoholic cardiomyopathy may develop, which presents with dilation and impaired contractility of the left or both ventricles. Endomyocardial biopsies of patients with alcoholic cardiomyopathy reveal in up to 30% of all cases myocarditis with lymphocytic infiltrates.

TREATMENT: Abstinence after development of milder heart failure can stop progression or even reverse symptoms in some cases, otherwise severe heart failure ensues leading to a poor prognosis. Except abstinence, treatment of alcoholic cardiomyopathy is based on the regimen of therapy for heart failure to reduce the size of the dilated heart and to mitigate the symptoms of heart failure.

Coronary artery disease modifies left ventricular remodelling due to heavy alcohol consumption.

Kajander OA, Kupari M, Laippala P, Penttila A, Karhunen PJ.

Medical School, University of Tampere, and Tampere University Hospital, Finland.

Alcohol Clin Exp Res 2001 Feb;25(2):246-52 Abstract quote

BACKGROUND: Coronary artery disease (CAD) and excessive alcohol use can both damage the myocardium. Their combined effect on the heart muscle has not been characterized. We set out to assess whether the presence of CAD modifies the effects of chronic alcohol consumption on the left ventricular (LV) structure in middle-aged men.

METHODS: A postmortem examination was performed on 700 Finnish men (age range, 33-70 years) who experienced a sudden, nonhospital death. A coronary arteriography and measurement of the LV wall thickness, cavity area, and ratio by planimetry of transversal ventricular slices were done at the autopsy. The men were grouped by the most severe coronary artery diameter stenosis (<30%, 30-60%, >60%) and by daily alcohol dose (<12 g, 12-72 g, 72-180 g, >180 g) estimated by a structured interview of their lifetime partner.

RESULTS: Analysis by ANCOVA, adjusted for age, body size, smoking, hypertension, and diabetes, showed a statistically significant interaction between the effects of coronary artery stenosis and daily alcohol dose on the LV cavity area (p = 0.037) and on the LV wall thickness/cavity area ratio (p = 0.018). In the group with X30% stenosis, the LV wall thickness/cavity area ratio (mean +/- SEM) increased from 1.6 +/- 0.2 mm/cm2 in men drinking <12 g/day to 6.2 +/- 1.4 mm/cm2 in men drinking 72-180 g/day (p = 0.021). A similar trend was seen in men with 30-60% coronary stenosis (p = 0.32). By contrast, in men with >60% coronary stenosis, the LV wall thickness/cavity area ratio decreased with increasing daily alcohol use from 2.2 +/- 0.3 to 1.4 +/- 0.1 mm/cm2 (p = 0.27).

CONCLUSIONS: CAD modulates the effects of alcohol on the heart muscle. Heavy drinking results in concentric LV remodelling in men with no or only mild coronary artery stenoses whereas an opposite trend is seen in men with severe coronary artery obstructions. The mechanism of the interaction remains unknown.

 

HISTOPATHOLOGICAL VARIANTS CHARACTERIZATION
LIVER  

Clinicopathological analysis of alcoholic liver disease complicating chronic type C hepatitis.

Noguchi O, Yamaoka K, Ikeda T, Tozuka S, Sakamoto S, Kanayama M, Uchida T.

Department of Internal Medicine, Yokosuka Kyosai Hospital, Japan.

Liver 1991 Aug;11(4):225-30 Abstract quote

Seventy-six chronic alcoholics in Japan were evaluated for histological changes of liver needle biopsies, Chiron C100 antibody (C-100) for hepatitis C virus, as well as clinical and laboratory data.

In biopsies, the presence of necroinflammations within the parenchyma, lymphocytic reaction in the portal tracts, or both, might indicate non-A, non-B (NANB) chronic hepatitis. Using these histological criteria, the patients were previously classified into two groups: alcoholic liver disease (ALD) alone and ALD complicating NANB chronic hepatitis. The C100-positive ratio was found to be 12% in the former group and 69% in the latter. Further clinical and laboratory comparison revealed that there were significant differences in gamma-glutamyl transpeptidase, gamma-globulin, and adenosine deaminase levels in the sera between the ALD alone and the ALD complicating NANB chronic hepatitis groups.

Since some chronic alcoholics are also affected by chronic type C hepatitis, detailed evaluations of the liver biopsy and C-100 assay are required for the differentiation of these hepatic disorders.

A histopathological study of alcoholics with chronic HCV infection: comparison with chronic hepatitis C and alcoholic liver disease.

Uchimura Y, Sata M, Kage M, Abe H, Tanikawa K.

Second Department of Medicine, Kurume University School of Medicine, Japan.

Liver 1995 Dec;15(6):300-6 Abstract quote

To clarify the relationship between hepatitis C virus infection and excessive alcohol intake, we carried out histological examination of the liver in 46 alcoholics with chronic hepatitis C virus infection and compared the findings in 55 patients with chronic hepatitis C, 38 with alcoholic liver disease, and 27 with chronic hepatitis B.

The majority of alcoholics with chronic hepatitis C virus infection displayed virus-related histological changes very similar to those in chronic hepatitis C, including frequent lymphoid follicles (34.7%) or aggregates (93.3%) in the portal tracts, mild necroinflammatory change (76.1%) in the parenchyma, and lymphocytosis in sinusoids (83.7%). Liver cell dysplasia and irregular regenerative activity of hepatocytes were rarely observed. The effects of alcohol on the liver were found to be minimal in the majority.

These findings could suggest that the hepatic injury in the majority of alcoholics with chronic hepatitis C virus infection in Japan is due to persistent hepatitis C virus infection rather than to alcoholic injury. In addition, our study disclosed that the perivenular fibrosis which is designated as a histological characteristic of alcoholic liver disease is frequently observed in chronic hepatitis C. These similarities suggest that a similar fibrogenesis is present in chronic hepatitis C and alcoholic liver disease.

A clinicopathological study of acute hepatitis in heavy drinkers, unrelated to hepatitis A, B, or C viruses.

Miyano S, Maeyama S, Iwaba A, Ogata S, Koike J, Kishi M, Uchikoshi T.

Department of Pathology, St. Marianna University School of Medicine, Kawasaki, Japan.

Alcohol Clin Exp Res 2001 Jun;25(6 Suppl):69S-74S Abstract quote

BACKGROUND: There are six histological classifications of alcoholic liver disease (ALD) in Japan. However, it is unclear whether all cases of the disease conform to these criteria. This study investigated the clinicopathological features of eight histologically unusual cases of ALD.

METHODS: The characteristic features of alcohol drinking behavior, subjective and objective symptoms, laboratory data on admission, and progress after admission were analyzed for eight patients with acute-onset hepatitis.

RESULT: The eight patients showed histologically acute hepatitis, with much spotty necrosis that contained granular ceroid pigment by Kupffer cells, which indicated acute parenchymal damage of the liver, but with no Mallory bodies and unremarkable intrasinusoidal neutrophilic infiltration. The only etiological factor for all the cases was habitual alcohol consumption, with increased consumption just before the onset of symptoms. In five cases that were tested, the patients were negative for hepatic viral markers, which included hepatitis G virus RNA and TT virus DNA.

CONCLUSION: Some cases of ALD may not conform to the current histological classifications in either Japan or Western countries. It seems natural to consider that these cases are developed by other, unknown causes that overlap with ALD rather than as a result of damage from alcoholic overload.


Portal lymphocytic infiltrate in alcoholic liver disease.

Colombat M, Charlotte F, Ratziu V, Poynard T.

Services Central d'Anatomie Pathologique and d'Hepato-Gastroenterologie, Groupe Hospitalier Pitie-Salpetriere, Paris, France.

Hum Pathol 2002 Dec;33(12):1170-4 Abstract quote

The aim of this study was to estimate the frequency of lymphocytic portal infiltrate in human alcoholic liver disease and to determine whether it was correlated with liver injury.

This retrospective study included 200 consecutive patients referred between February 1996 and March 2001 to the Service Central d'Hepato-Gastroenterologie at Groupe Hospitalier Pitie-Salpetriere Hospital, Paris, France.

The inclusions criteria were as follows: (1) daily alcohol consumption greater than 40 g; (2) appropriate serological exclusion of B and C viral hepatitis; and (3) available liver biopsy specimen. Autoimmune hepatitis was excluded in all patients with the aid of a consensus scoring system. Forty percent of the patients had a predominantly lymphocytic portal infiltrate. On stepwise logistic regression of the predictive value of the 5 variables (gender, age, daily alcohol consumption, steatosis, and portal and septal fibrosis index), only 2 statistically independent predictors of predominant lymphocytic portal infiltrate were identified: portal and septal fibrosis index (P <.05) and age (P <.05).

In conclusion, predominantly portal lymphocytic infiltrate occurs frequently in alcoholic liver disease, even in patients without serological markers of B and C viral hepatitis. Moreover, after adjustment for age, portal and septal fibrosis index remains significantly associated with the presence of a predominantly lymphocytic portal infiltrate. These results suggest that lymphocytes may play a role in the pathogenesis of alcohol-induced liver fibrosis.

 

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES

Nonalcoholic steatohepatitis.

Reid AE.

Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

Gastroenterology 2001 Sep;121(3):710-23 Abstract quote

Nonalcoholic steatohepatitis (NASH) is a condition characterized by hepatomegaly, elevated serum aminotransferase levels, and a histologic picture similar to alcoholic hepatitis in the absence of alcohol abuse.

Most patients with NASH are obese women, and many have diabetes mellitus, hypercholesterolemia, or hypertriglyceridemia. NASH has also been associated with a number of metabolic conditions, surgical procedures, and drug treatments. Most patients are asymptomatic. The most common sign of NASH is hepatomegaly. Stigmata of chronic liver disease are rare.

Laboratory abnormalities include a 2-4-fold elevation of serum aminotransferase levels; other liver function test results are usually normal.

Histologically, there is moderate to severe macrovesicular steatosis and lobular hepatitis with necrosis or ballooning degeneration and/or fibrosis. The pathogenesis of NASH is poorly understood, but lipid peroxidation and oxidative stress are the leading culprits.

The natural history of NASH is unknown, but NASH seems to be a stable disease in most patients. Treatment of NASH is unproven, but weight reduction is recommended in obese patients. Small pilot studies of several drugs have shown promise, but large randomized clinical trials are awaited. Orthotopic liver transplantation is the treatment of choice for end-stage liver disease secondary to NASH.

 

PROGNOSIS AND TREATMENT CHARACTERIZATION
GENERAL  
The long-term course of alcoholism, 5, 10 and 16 years after treatment.

Mann K, Schafer DR, Langle G, Ackermann K, Croissant B.

Central Institute of Mental Health, Mannheim, University of Heidelberg, Heidelberg, Germany.
Addiction. 2005 Jun;100(6):797-805. Abstract quote  

ABSTRACT Aims To discover the long-term stability of drinking behaviour following an in-patient treatment episode.

Design Three follow-up periods were used at 5, 10 and 16 years. The patients were classified as being abstinent, improved or unimproved on the basis of self-reported drinking behaviour. Patients who could not be interviewed at follow-up were classified as unimproved.

Setting An alcohol dependence treatment programme at the University Hospital Tuebingen, Germany.

Participants We were able to locate all 96 patients at the 16-year follow-up. Seventy were alive and 26 had died. We collected information from 59 of the 70 surviving patients. The remaining 11 patients could be located and were definitely alive.

Findings Thirty-eight of the 70 patients were abstinent, 10 were improved and 22 (including the 11 living patients without further information) were classified as unimproved.

Our main finding indicates that the so-called 'improved drinking' is very inconsistent over time. In contrast, the abstinent and unimproved patients were much more stable in their drinking behaviour.

Conclusions This study extends our knowledge of the drinking trajectory and outcome from only a few years of follow-up to 16 years. Complete abstinence and unimproved drinking behaviour were the most stable drinking patterns observed over the long term, confirming study results obtained primarily from English-speaking countries.
TREATMENT  
DRUGS  
Development of medications for alcohol use disorders: recent advances and ongoing challenges.

Litten RZ, Fertig J, Mattson M, Egli M.

Division of Treatment and Recovery Research, National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Room 2041, Bethesda, MD 20852-1705, USA.
Expert Opin Emerg Drugs. 2005 May;10(2):323-43. Abstract quote  

During the past decade, efforts to develop medications for alcoholism have burgeoned. Three agents, disulfiram, naltrexone and acamprosate, are now approved in a large number of countries. Although many patients have benefited from existing medications, their effects are moderate, and some alcoholics fail to respond to them. A host of new agents are currently under active investigation. Critical barriers must be overcome to ensure that future efforts in the development of medications for alcohol use disorders reach full fruition.

These challenges include: establishing key targets for drug discovery; validating animal and human screening models; and developing biomarkers to help predict treatment success. In addition, it is important to formulate methodological and statistical strategies to efficiently conduct alcohol pharmacotherapy trials; to specify genetic and phenotypic patient characteristics associated with efficacy and safety for lead compounds; to forge productive alliances among governmental agencies, the pharmaceutical industry and academic researchers to further drug development; and, ultimately and perhaps most difficult, to engage the practitioner community to incorporate medications into the alcohol treatment process.
LIVER TRANSPLANTATION  

Liver transplantation for alcoholic cirrhosis: long term follow-up and impact of disease recurrence.

Bellamy CO, DiMartini AM, Ruppert K, Jain A, Dodson F, Torbenson M, Starzl TE, Fung JJ, Demetris AJ.

Department of Pathology, Edinburgh University Medical School, Scotland.

Transplantation 2001 Aug 27;72(4):619-26 Abstract quote

BACKGROUND: Alcoholic liver disease has emerged as a leading indication for hepatic transplantation, although it is a controversial use of resources. We aimed to examine all aspects of liver transplantation associated with alcohol abuse.

METHODS: Retrospective cohort analysis of 123 alcoholic patients with a median of 7 years follow-up at one center.

RESULTS: In addition to alcohol, 43 (35%) patients had another possible factor contributing to cirrhosis. Actuarial patient and graft survival rates were, respectively, 84% and 81% (1 year); 72% and 66% (5 years); and 63% and 59% (7 years). After transplantation, 18 patients (15%) manifested 21 noncutaneous de novo malignancies, which is significantly more than controls (P=0.0001); upper aerodigestive squamous carcinomas were overrepresented (P=0.03). Thirteen patients had definitely relapsed and three others were suspected to have relapsed. Relapse was predicted by daily ethanol consumption (P=0.0314), but not by duration of pretransplant sobriety or explant histology. No patient had alcoholic hepatitis after transplantation and neither late onset acute nor chronic rejection was significantly increased. Multiple regression analyses for predictors of graft failure identified major biliary/vascular complications (P=0.01), chronic bile duct injury on biopsy (P=0.002), and pericellular fibrosis on biopsy (P=0.05); graft viral hepatitis was marginally significant (P=0.07) on univariate analysis.

CONCLUSIONS: Alcoholic liver disease is an excellent indication for liver transplantation in those without coexistent conditions. Recurrent alcoholic liver disease alone is not an important cause of graft pathology or failure. Potential recipients should be heavily screened before transplantation for coexistent conditions (e.g., hepatitis C, metabolic diseases) and other target-organ damage, especially aerodigestive malignancy, which are greater causes of morbidity and mortality than is recurrent alcohol liver disease.

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