Important Note: The following information is provided for your education. It should not be relied upon for personal diagnosis or treatment. If you believe that a particular therapy applies to you or someone you care about, be sure to consult a doctor before trying it.
   

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Previous Research on Alcoholic Liver Disease:
2002-2006   
The Alcoholic Liver Disease File also contains summaries of past research that has shown promise and may still be standard practice among many physicians. To download earlier research findings on Alcoholic Liver Disease, click HERE.
 

Latest Research on
Alcoholic Liver Disease
  
Arch Intern Med. 2008 Jun 9;168(11):1188-99.
Improvement of physical health and quality of life of alcohol-dependent individuals with topiramate treatment: US multisite randomized controlled trial.
Johnson BA, Rosenthal N, Capece JA, Wiegand F, Mao L, Beyers K, McKay A, Ait-Daoud N, Addolorato G, Anton RF, Ciraulo DA, Kranzler HR, Mann K, O'Malley SS, Swift RM; Topiramate for Alcoholism Advisory Board; Topiramate for Alcoholism Study Group.
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA 22908-0623, USA. bankolejohnson@virginia.edu

BACKGROUND: Topiramate can improve drinking outcomes via a hypothesized mechanism of facilitating gamma-aminobutyric acid function and inhibiting glutaminergic pathways in the corticomesolimbic system. We sought to determine whether topiramate's antidrinking effects are bolstered by improvements in physical and psychosocial well-being. METHODS: In a 17-site, 14-week, double-blind, randomized controlled trial, we compared the effects of topiramate (up to 300 mg/d) vs placebo on physical health, obsessional thoughts and compulsions about using alcohol, and psychosocial well-being among 371 alcohol-dependent subjects who received weekly adherence enhancement therapy. RESULTS: Topiramate was more efficacious than placebo in reducing body mass index (calculated as weight in kilograms divided by height in meters squared) (mean difference, 1.08; 95% confidence interval [CI], 0.81-1.34; P < .001), all liver enzyme levels (P < .01 for all comparisons), plasma cholesterol level (mean difference, 13.30 mg/dL; 95% CI, 5.09-21.44 mg/dL; P = .002), and systolic (mean difference, 9.70 mm Hg; 95% CI, 6.81-12.60 mm Hg; P < .001) and diastolic (mean difference, 6.74 mm Hg; 95% CI, 4.57-8.90 mm Hg; P < .001) blood pressure to about prehypertension levels-effects that might lower the risk of fatty liver degeneration and cirrhosis as well as cardiovascular disease. Topiramate compared with placebo significantly (P < .05 for all comparisons) decreased obsessional thoughts and compulsions about using alcohol, increased subjects' psychosocial well-being, and improved some aspects of quality of life, thereby diminishing the risk of relapse and longer-term negative outcomes. Paresthesia, taste perversion, anorexia, and difficulty with concentration were reported more frequently for topiramate than for placebo. CONCLUSION: Topiramate appears to be generally effective at improving the drinking outcomes and physical and psychosocial well-being of alcoholic subjects.

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Eur J Med Res. 2008 May 26;13(5):205-8.
Safety of long-term lopinavir plasma-levels in patients with liver disease.
Langmann P, Hubert C, Heinz W, Trein A, Schnaitmann E, Leyh M, Klinker H, Winzer R.
Private-Praxis, Karlstadt, Germany. p_langmann@yahoo.de

Chronic liver disease is often found in HIV infected patients. LPV as first choice drug is often used over long time periods. TDM as a tool in patients care is important but the knowledge of LPV-plasma-levels in patients with chronic liver disease remain uncertain. With this retrosepective analysis we want to show if there are differences in LPV-plasma-levels between patients with and without chronic liver diseases over a long-time period. LPV-plasma-levels were analysed with an HPLC-based methode. The LPV-plasma-levels over the time course in patients with chronic liver disease (n = 30) and patients without liver disease (n = 38) was evaluated. Liver function tests, CD4-cell count and HI-viral load was also correlated with liver disease. The LPV plasma-levels of n = 450 samples from 30 patients with liver disease (Hepatitis B: n = 17, Hepatitis C: n = 16, Alcoholic liver disease: n = 7) were determined over 18.7 +/- 16,3 months (1 - 48.5 months). A median of 10 samples per patient was eligible (2 - 50 samples). There are no significant differences according to liver disease in LPV-plasma levels (mean Ctrough without: 5917 +/- 4811 ng/ml, mean Ctrough with liver-disease: 6564 +/- 4517 ng/ml, p > 0.05). The intraindividual and interindividual variation of LPV-plasma levels, CD-4 increase, HI-virus suppression and liver tests in patients with and without liver disease is comparable. In this clinical setting no differences in LPV-plasma levels between patients with and without chronic liver disease could be demonstrated. LPV-therapy in patients with chronic liver disease is therefore safe. In patients with impaired liver function TDM is a helpful tool for dose adjustment.

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Curr Opin Gastroenterol. 2008 May;24(3):328-38.
Alcohol and the liver.
Reuben A.
Liver Service, Division of Gastroenterology and Hepatology, and Liver Transplant Program, Medical University of South Carolina, Charleston, South Carolina, USA. reubena@musc.edu

PURPOSE OF REVIEW: To update the reader with advances in epidemiology, genetics, detection, pathogenesis and therapy of alcohol-related liver disease. RECENT FINDINGS: Ill-health due to alcohol abuse is improving in some nations but deteriorating in others. Oxidative and nitrosative stress are key to the pathogenesis of alcoholic liver disease, and there is now greater emphasis than previously on their development and role of cytochrome P450 2E1, on mitochondrial stress and disruption, (including elucidation of mitochondrial protection mechanisms) disturbance of signaling pathways and involvement of extrahepatic mediators like adiponectin. Treatment of alcoholic liver disease has stagnated, but transplantation is still favored and debated for end-stage cirrhosis. SUMMARY: Basic and clinical research into the mechanisms of alcoholic liver disease is making headway, but has yet to produce safe and effective therapies for alcoholic hepatitis and for reversing cirrhosis.

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Presse Med. 2008 Apr 2 [Epub ahead of print]
[Managing comorbidities in hepatology: toward a more holistic medicine.]
[Article in French]
Couzigou P, Foucher J, Castera L, De Ledinghen V.
Service hépato-gastroentérologie, Hôpital du Haut Lévêque, F-33604 Pessac, France.

Approximately 20% of patients infected with the hepatitis B or C virus (HBV and HCV) develop cirrhosis of the liver. It is essential, especially for preventive purposes, to test for related etiological factors, especially excess alcohol consumption, metabolic syndrome, and obesity. The frequency of these health problems and their hepatic tropism explain these frequent associations. In patients with chronic HBV and HCV, alcohol consumption and metabolic syndrome increase the risk of fibrosis; in those with HCV, they also reduce the likelihood of treatment response. In patients with alcoholic hepatitis, overweight increases cirrhotic risk. If cytolysis persists after the identified factor is controlled, another etiologic factor must be sought and treated. For patients with excess alcohol consumption and similarly those with metabolic syndrome, it is essential to differentiate between dependency, which is more difficult to treat, and other risk situations, for which the efficacy of a brief intervention by the physician has been demonstrated. In this more holistic approach, the physician treats a person with liver disease, rather than just a diseased liver.

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Alcohol Alcohol. 2008 Apr 2 [Epub ahead of print]
The Pervading Influence of Alcoholic Liver Disease in Hepatology.
Williams R.
Institute of Hepatology, University College London Medical School, 69–75 Chenies Mews, London, WC1E 6HX, UK.

Rising levels of alcohol consumption in the UK are leading to substantial increases in morbidity and mortality from liver disease. Drinking is starting at an earlier age with binging an increasing common pattern, and women are overtaking men in the consumption. Manifestations of liver damage range from fatty liver to end-stage cirrhosis, but it is the increasing number of cases presenting with an acute alcoholic hepatitis (AAH) that are the cause for greatest concern. Development of well-validated prognostic scoring systems (Maddrey Modified Discriminant Function, Glasgow Alcohol Score) makes it possible to select those patients with AAH who are most likely to respond to corticosteroids. The results of early pilot studies of a number of anti-TNF agents are encouraging and with infliximab, reduction in portal pressure has been demonstrated to be consequent on controlling inflammatory processes in the liver. For those deteriorating to the stage of liver failure, artificial live
r support with MARS is of value in correcting major pathophysiological disturbances and as a bridge to liver transplantation, the results of which both for end-stage alcoholic cirrhosis and for AAH-of which there is limited experience, are excellent. Even as the stringent regulatory measures needed to control rising alcohol consumption are introduced by government, the burden of liver disease in the UK will remain high for years to come.

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J Gastroenterol Hepatol. 2008 Mar;23 Suppl 1:S60-2.
Treatment of severe forms of alcoholic hepatitis: where are we going?
Mathurin P, Louvet A, Dharancy S.
Service d'Hépato-Gastroentérologie, Hôpital Huriez Lille, Lille, France. p-mathurin@chru-lille.fr

Alcoholic hepatitis (AH) is observed in approximately 20% of heavy drinkers. The treatment of AH remains one of the main challenges to clinicians involved in the management of severe alcoholic liver disease. Corticosteroids improved the short-term survival of patients with severe AH. Nevertheless, the efficacy of corticosteroids is still considered controversial for some authors. Pentoxifylline may be considered an alternative to corticosteroids. Early identification of subjects with substantial risk of death according to the Lille model will improve management of patients suffering from severe AH and will aid in the design of future studies for alternative therapies. Alternative therapies are required to improve the prognosis of patients with a severe form of AH. Progress in understanding the pathogenesis of AH is opening up an exciting new era and is lending impetus to future evaluation of new drugs targeting the tumor necrosis factor pathways.

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Liver Transpl. 2008 Feb;14(2):235-9.
The effect of liver transplantation on autonomic dysfunction in patients with end-stage liver disease.
Carey EJ, Gautam M, Ingall T, Douglas DD.
Division of Transplantation Medicine, Mayo Clinic Arizona, Phoenix, AZ 85054, USA. carey.elizabeth@mayo.edu

Autonomic dysfunction is a recognized complication of end-stage liver disease (ESLD), but there is little information on how liver transplantation (LT) affects this problem. We sought to prospectively evaluate autonomic function in patients with ESLD before and after LT. Autonomic reflex screen (ARS) was performed on 30 patients with ESLD prior to transplantation. A 10-point composite autonomic score (CAS) was calculated from these data. ARS was repeated after LT, and these scores were compared with the pre-LT ARS. Thirty patients (25 male, 5 female) with cirrhosis that were listed for LT were enrolled in the study and underwent ARS prior to LT. The average age was 55.4 +/- 9.1 years. Indications for LT included hepatitis C virus (14), cryptogenic cirrhosis (5), alcoholic cirrhosis (4), and other (7). The mean native Model for End-Stage Liver Disease (MELD) score at ARS was 17.0 +/- 5.0. Prior to LT, 86.7% of patients had evidence of autonomic dysfunction. Mean CAS was 2.7 +/- 2.2. Sudomotor function was disturbed in 66%, parasympathetic function was disturbed in 57%, and adrenergic function was disturbed in 37%. There was no relationship between pre-LT CAS and age, gender, diabetes, etiology of liver disease, or MELD score. Twenty-one patients (17 male, 4 female) had repeat ARS a mean of 9 +/- 6.2 months after LT. The mean native MELD score at the time of ARS testing was 18.1 +/- 4.3. Mean pre-LT CAS in this group was 3.0 +/- 2.4. Pretransplant CAS was not related to age, gender, diabetes, or MELD score. Autonomic dysfunction improved after LT (CAS pre-LT, 3.0, versus CAS post-LT, 1.9, P = 0.02). There was no relationship between post-LT CAS and age, gender, diabetes, etiology of liver disease, immunosuppression, or type of transplant. In conclusion, autonomic dysfunction is common in patients with ESLD, with over 86% having abnormal testing. Sixty-three percent of patients with cirrhosis with autonomic dysfunction show improvement after LT.

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Acta Gastroenterol Belg. 2008 Jan-Mar;71(1):42-6; discussion 47.
The risk of surgery in patients with cirrhosis.
Francoz C, Durand F.
Pôle des Maladies de l'Appareil Digestif, Service d'Hépatologie, Unité de Réanimation Hépato-Digestive, Hôpital Beaujon, Clichy, France.

Several reasons result in the finding that patients with cirrhosis need surgery more often than other patients groups. Patients with cirrhosis frequently have comorbidities resulting in gastrointestinal, lung or cervical cancer, among others. Independent of cirrhosis, surgical resection may be the best alternative for a number of those malignancies. Comorbidities may also result in an increased incidence of vascular complications (such as lower extremity atherosclerosis and coronary stenosis) some of them being potential indications for surgery. Patients with alcoholic cirrhosis are more frequently subjected to trauma and bone fractures. Ascites leads to umbilical hernia which can be strangulated or ruptured. Emergency surgery may be needed in this context. Finally, a significant proportion of patients with cirrhosis develop hepatocellular carcinoma (HCC) during the course of the disease. Surgical resection remains a first line option for HCC. While reliable guidelines have been proposed for surgical resection of HCC and liver transplantation, no precise guidelines are available for other aspects of surgical management during cirrhosis. Specific surgical procedures such as hepatectomy and transplantation are concentrated in highly specialised centres, where detailed evaluation is relatively easy to obtain. In contrast, more general surgical procedures, either abdominal or non abdominal, are performed in various centres, making it more difficult to obtain detailed evaluation and draw recommendations. General surveys are still needed to precisely assess the risk of non-specific surgery in patients with cirrhosis, to identify risk factors and to propose reliable guidelines.

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Ann Hepatol. 2008 Jan-Mar;7(1):5-15.
Treatment of alcoholic liver disease.
Barve A, Khan R, Marsano L, Ravindra KV, McClain C.
Department of internal medicine, University of Louisville Medical Center, Louisville, KY 40292, USA.

Alcoholic Liver Disease (ALD) is a major cause of morbidity and mortality both in the United States and worldwide. In the United States, it is projected that over 2,000,000 persons have ALD, and the mortality for cirrhosis with superimposed alcoholic hepatitis is much worse than that of many common types of cancer. Unfortunately, there is no FDA approved therapy for ALD. We have made major strides in the last decade in identifying mechanisms for the development of liver injury in ALD, and therapies are evolving directed at specific mechanisms. It is clear that life style modification with abstinence, cessation of smoking and weight loss (if overweight) are beneficial. It is also clear that most patients with advanced liver disease have some form of malnutrition, and nutritional supplementation is of benefit. Patients with alcoholic hepatitis that is relatively severe in nature, but not complicated by issues such as infection or GI bleeding, appear to benefit from steroids. A
drop in bilirubin should be monitored in steroid treated patients. Pentoxifylline appears to be beneficial in patients with alcoholic hepatitis, especially those with early hepatorenal syndrome. A variety of other agents such as PTU, lecithin, colchicine, and anabolic steroids are probably not effective. Complementary and alternative medicine agents such as zinc, milk thistle, and SAM have great therapeutic rationale. Results of ongoing NIH studies evaluating agents such as specific anti-TNF's, SAM and Milk Thistle are eagerly awaited. Transplantation is clearly an option for end stage ALD in patients who are abstinent.

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Subst Abuse Treat Prev Policy. 2008 Jan 25;3:1.
Magnesium treatment in alcoholics: a randomized clinical trial.
Poikolainen K, Alho H.
Finnish Foundation for Alcohol Studies, Helsinki, Finland. kari.poikolainen@stakes.fi.

BACKGROUND: Magnesium (Mg) deficiency is common among alcoholics. Earlier research suggests that Mg treatment may help to normalize elevated enzyme activities and some other clinically relevant parameters among alcoholics but the evidence is weak. METHODS: The effect of Mg was studied in a randomized, parallel group, double-blind trial. The patients were first treated for alcohol withdrawal symptoms and then received for 8 weeks either 500 mg of Mg divided into two tablets or matching placebo. Measurements were made at the beginning and in the end of the Mg treatment period. The primary outcome was serum gamma-glutamyltransferase (S-GGT) activity; secondary outcomes included aspartate-aminotransferase (S-AST) and alanine-aminotransferase (S-ALT) activity. RESULTS: The number of randomized patients (completers) was 64 (27) in the treatment and 54 (31) in the control group. In intention-to-treat-analyses and in most analyses of study completers, there were no significant differences between the Mg-treated and placebo groups in the outcome variables. When baseline serum Mg level, coffee intake, and the number of unused Mg tablets were controlled for in a multivariate regression model, after-treatment serum Mg levels were found to be higher among the Mg-treated group than in the placebo group (t-test 3.334, df = 53, p = 0.002). After controlling for age, body weight, baseline alcohol intake, subsequent change in alcohol intake and baseline S-AST, the after-treatment S-AST levels were found to be lower among the Mg-treated group than in the placebo group (t-test 2.061, df = 49, p = 0.045). CONCLUSION: Mg treatment may speed up the S-AST decrease in compliant patients. This might decrease the risk of death from alcoholic liver disease. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT00325299.

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Liver Transpl. 2008 Jan;14(1):18-24. Comment in: Liver Transpl. 2008 Jan;14(1):9-10.
Greater travel time to a liver transplant center does not adversely affect clinical outcomes.
Firozvi AA, Lee CH, Hayashi PH.
Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO, USA.

The effect of patient travel time to a transplant center on outcomes is unknown. We compared outcomes between patients living >3 hours (Group A) vs. <or=3 (Group B) hours drive away. Adult, nonacute liver failure patients entering transplant evaluation from February 27, 2002 to January 31, 2005 were analyzed. Of 166 patients, 126 (75.5%) were listed and 66 (39.5%) received transplantation. Outcomes of interest were >90 days to list, listing, survival while listed, transplantation, and posttransplantation survival. Covariates included Model for End-Stage Liver Disease (MELD) score, hepatocellular carcinoma (HCC), alcoholic liver disease, insurance type, and psychosocial score. There were 38 (23%) patients in Group A and 128 (77%) in Group B. Median MELD scores were 14.5 (range, 6-36) for Group A and 14.0 (range, 7-32) for Group B (p = 0.20). Groups were similar for age, gender, diagnosis, psychosocial score, insurance, and HCC variables. Group A was not independently associated with >90 days to list (odds ratio, 0.98; 95% confidence interval [CI], 0.4-2.4). Kaplan-Meier cumulative probabilities for listing, transplantation, and 1-yr posttransplantation survival were similar (A vs. B: 0.77 vs. 0.83, 0.70 vs. 0.69, and 0.85 vs. 0.86, respectively; all p values >0.05). Being in Group A remained insignificant in terms of probability of listing, transplantation, and posttransplantation survival by Cox proportional hazard modeling. Survival on the list was significantly better for Group A (A: 1.0, B: 0.55; p = 0.02). Fewer patients at high MELD score in Group A and referral biases may explain this difference. In conclusion, after entering evaluation, patients living >3 hours away from a transplant center have comparable outcomes to those living closer. (c) 2007 AASLD.

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Eur Surg Res. 2008;40(1):7-13. Epub 2007 Aug 23.
Single-center experience on liver transplantation for hepatocellular carcinoma arising in alcoholic cirrhosis: results and ethical issues.
Sotiropoulos GC, Beckebaum S, Lang H, Frilling A, Molmenti EP, Cicinnati VR, Saner FH, Erim Y, Baba HA, Malagó M, Broelsch CE.
Department of General, Visceral, and Transplantation Surgery, University Hospital Essen, Essen, Germany. Georgios.sotiropoulos@uni-essen.de
  
BACKGROUND: Liver transplantation is currently recognized as the optimal treatment for both early hepatocellular carcinoma in the setting of cirrhosis (HCC) as well as for alcoholic liver disease (ALD). The purpose of this study was to evaluate the outcome of patients with HCC and ALD in the absence of viral hepatitic infections. METHODS: Twelve recipients were transplanted with a diagnosis of HCC and ALD in the absence of viral hepatitis during a 6-year period. Nine received deceased donor livers, and 3 live donor grafts. Our results were compared to those obtained by a search of the world literature. RESULTS: The postoperative course was uneventful in all but one patient. All recipients experienced a good quality of life postoperatively. Three-year overall and recurrence-free survival rates were 82 and 73%, respectively. Nine patients are currently alive, after a median follow-up of 29 months. CONCLUSION: This is the first study to evaluate liver transplantation for HCC in ALD. Although outcomes are excellent, the evaluation of patients with ALD and HCC constitutes a challenging topic in transplantation surgery, especially when live liver donation is considered. An interdisciplinary structured approach is recommended, with special emphasis on ethical considerations. (c) 2008 S. Karger AG, Basel.
 
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Hepatology. 2007 Dec;46(6):2032-9.
Determinants of alcohol use and abuse: Impact of quantity and frequency patterns on liver disease.
Zakhari S, Li TK.
National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-9304, USA. szakhari@mail.nih.gov
 
More than 70% of alcohol is consumed by 10% of the population in the United States. Implicit in this statistic is that tremendous variation in the pattern of drinking (quantity, frequency, and duration) exists among alcohol consumers. Individuals who are binge or chronic drinkers will have different health outcomes than social drinkers. Therefore, knowing the pattern of drinking will shed light on how severely individuals are alcohol-dependent and on the extent of liver damage. Thus, these parameters assume particular relevance for the treatment-providing physician. Genetic factors contribute substantially to differences in alcohol metabolism. Variations in the activities of the alcohol-metabolizing enzymes, cytosolic alcohol dehydrogenase and mitochondrial aldehyde dehydrogenase, in part determine blood alcohol concentration, thereby contributing to the predisposition to becoming alcohol-dependent and to susceptibility to alcohol-induced liver damage. Chronic alcohol consumption induces cytochrome P450 2E1, a microsomal enzyme that metabolizes alcohol at high concentrations and also metabolizes medications such as acetaminophen and protease inhibitors. Alcohol metabolism changes the redox state of the liver, which leads to alterations in hepatic lipid, carbohydrate, protein, lactate, and uric acid metabolism. The quantity and frequency of alcohol consumption severely impact the liver in the presence of comorbid conditions such as infection with hepatitis B or C and/or human immunodeficiency virus, type 2 diabetes, hemochromatosis, or obesity and thus have implications with respect to the extent of injury and response to medications. Conclusion: Knowledge of the relationships between the quantity, frequency, and patterns of drinking and alcoholic liver disease is limited. A better understanding of these relationships will guide hepatologists in managing alcoholic liver disease.
 
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Transpl Int. 2007 Nov 21 [Epub ahead of print]
Long-term results after liver transplantation.
Pfitzmann R, Nüssler NC, Hippler-Benscheidt M, Neuhaus R, Neuhaus P.
Department of General, Visceral and Transplantation Surgery, Charité, Campus Virchow-Klinikum, University Medicine Berlin, Berlin, Germany.
 
Liver transplantation (OLT) has become a successful surgical therapy for terminal liver failure. We here report about long-term results of OLT in a single center over a period of 15 years. Between 1988 and 2002, 1365 adult OLTs were performed. Mean follow-up was 103 +/- 56 months. Main indications for OLT were viral-induced cirrhosis (27.1%), alcoholic liver disease (21%), tumors (15.7%) and cholestatic liver disease (14.6%). Retransplantation was necessary in 120 (9.6%) patients because of initial nonfunction (26.9%), recurrence of underlying disease (20.2%), acute and chronic rejection (16.8%) or thrombosis of the hepatic artery (16.8%). 275 patients (22.1%) died. Causes of death included recurrence of disease (32.1%), infections (21.8%), de novo malignancies (13.5%) and cardiovascular disease (11.6%). Patient survival after OLT was 91.4%, 82.5%, 74.7% and 68.2% after 1, 5, 10 and 15 years, and graft survival was 85.8%, 75.3%, 67.3% and 61.7% after 1, 5, 10 and 15 years, re
spectively. Patient survival after retransplantation was 81.6%, 68.8% and 57.1% and 48.0% after 1, 5, 10 and 15 years. This analysis reveals excellent long-term results after OLT achieved in a single center.
 
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Liver Transpl. 2007 Nov;13(11 Suppl 2):S69-75.
Treatment of alcoholic liver disease.
Day CP.
Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle upon Tyne, UK.
 
Severe alcoholic steatohepatitis (ASH) is the major complication of advanced alcoholic liver disease (ALD) and has a high mortality even when treated with corticosteroids. Despite the importance of reactive oxygen species in the pathophysiology of ALD and ASH, antioxidants provide no benefit in the treatment of patients with ASH. Proinflammatory cytokines are important in the pathophysiology of ALD and might mediate most of the inflammatory aspects of these disorders. New treatment modalities in ASH might involve antagonism of proinflammatory cytokines such as tumor necrosis factor (TNF) by specific antibodies or other TNF-interfering treatment strategies. Propylthiouracil and S-adenosyl methionine may be beneficial to patients with alcoholic cirrhosis, but both require further randomized, controlled trials before their use can be recommended. Liver transplantation is an effective therapy for patients with advanced alcoholic cirrhosis who have not recovered after a period of a
bstinence.
 
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Clin Geriatr Med. 2007 Nov;23(4):905-21, viii.
Alcoholic liver disease in the elderly.
Seitz HK, Stickel F.
Department of Medicine & Center of Alcohol Research, Liver Disease and Nutrition, Salem Medical Center, University of Heidelberg, Zeppelinstrasse 11-33, D - 69121 Heidelberg, Germany. helmut_karl.seitz@urz.uni-heidelberg.de
 
Although per capita alcohol consumption, and thus the prevalence of alcoholic liver disease, decreases generally with age in Europe and in the United States, recently an increase in alcohol consumption has been reported in individuals over 65 years. Reasons explaining this observation may include an increase in life expectancy or a loss of life partners and, thus, loneliness and depression. Although ethanol metabolism and ethanol distribution change with age, and an elderly person's liver is more susceptible to the toxic effect of ethanol, the spectrum of alcoholic liver diseases and their symptoms and signs is similar to that seen in patients of all ages. However, prognosis of alcoholic liver disease in the elderly is poor. In addition, chronic alcohol consumption may enhance drug associated liver disease and may also act as a cofactor in other liver diseases, such as viral hepatitis and nonalcoholic fatty liver disease.
 
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Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003620. Update of:
Cochrane Database Syst Rev. 2005;(2):CD003620.
Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases.
Rambaldi A, Jacobs BP, Gluud C.
Copenhagen Trial Unit, Centre for Clinical Intervention Research, Cochrane Hepato-Biliary Group, Rigshospitalet, Dept. 3344, Blegdamsvej 9, Copenhagen, Denmark, DK-2100. arambaldi@hotmail.com
 
BACKGROUND: Alcohol and hepatotoxic viruses cause the majority of liver diseases. Randomised clinical trials have assessed whether extracts of milk thistle, Silybum marianum (L) Gaertneri, have any effect in patients with alcoholic and/or hepatitis B or C virus liver diseases. OBJECTIVES: To assess the beneficial and harmful effects of milk thistle or milk thistle constituents versus placebo or no intervention in patients with alcoholic liver disease and/or viral liver diseases (hepatitis B and hepatitis C). SEARCH STRATEGY: The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and full text searches were combined (July 2007). Manufacturers and researchers in the field were contacted. SELECTION CRITERIA: Only randomised clinical trials in patients with alcoholic and/or hepatitis B or C virus liver diseases (acute and chronic) were included. Interventions encompassed milk thistle at any dose or duration versus placebo or no intervention. The trials could be double blind, single blind, or unblinded. The trials could be unpublished or published and no language limitations were applied. DATA COLLECTION AND ANALYSIS: The primary outcome measure was mortality. Binary outcomes are reported as relative risks (RR) with 95% confidence interval (CI). Subgroup analyses were performed with regard to methodological quality. MAIN RESULTS: Eighteen randomised clinical trials assessed milk thistle in 1088 patients with alcoholic and/or hepatitis B or C virus liver diseases. The methodological quality was low: only 28.6% of the trials reported high methodological quality characteristics. Milk thistle versus placebo or no intervention had no significant effect on mortality (RR 0.78, 95% CI 0.53 to 1.15), complications of liver disease (RR 0.95, 95% CI 0.83 to 1.09), or liver histology. Liver-related mortality was significantly reduced by milk thistle in all trials (RR 0.50, 95% CI 0.29 to 0.88), but not in high-quality trials (RR 0.57, 95% CI 0.28 to 1.19). Milk thistle was not associated with a significantly increased risk of adverse events (RR 0.83, 95% CI 0.46 to 1.50). AUTHORS' CONCLUSIONS: Our results question the beneficial effects of milk thistle for patients with alcoholic and/or hepatitis B or C virus liver diseases and highlight the lack of high-quality evidence to support this intervention. Adequately conducted and reported randomised clinical trials on milk thistle versus placebo are needed.
 
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Hepatology. 2007 Oct;46(4):1302-4.
"I'll never touch it again, doctor!"--harmful drinking after liver transplantation.
Haber PS, McCaughan GW.
Drug Health Services, Royal Prince Alfred Hospital and Central Clinical School, University of Sydney, Camperdown NSW, Australia.
 
BACKGROUND: Alcohol relapse can negatively influence the outcome after liver transplantation (LT). The aim of our study was to identify factors that could be associated with the recurrence of harmful alcohol consumption after LT. METHODS: A total of 387 consecutive patients (23.8% women) who underwent LT for alcoholic cirrhosis in Geneva, Switzerland, and Lyon, France, between 1989 and 2005 were evaluated. Mean +/- SD age was 51.3 +/-7.5 years. Follow-up time was 61.2 +/- 47.5 months. Alcohol consumption relapse and potential factors associated with it were studied. RESULTS: The relapse rate of harmful alcohol consumption after LT was 11.9%. In univariate analysis, alcohol relapse was significantly associated with age greater than 50 years (P = .04), year of LT 1995 or earlier (P<.05), duration of abstinence less than 6 months (P = .02), presence of psychiatric comorbidities (P<.001), presence of a life partner (P<.05), and a high score on the High-Risk Alcoholism Relapse (HRAR) scale (P<.001). Multivariate logistic regression disclosed the following independent factors of relapse: duration of abstinence of less than 6 months (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.2-9.3) (P = .02); presence of psychiatric comorbidities (OR, 7.8; 95% CI, 3.1-20.0) (P<.001); and HRAR score higher than 3 (OR, 10.7; 95% CI, 3.8-30.0) (P = .001). In patients with none of these factors, alcohol relapse was 5%, while the presence of 1, 2, or 3 factors was associated with relapse rates of 18%, 64%, and 100% of the patients, respectively. CONCLUSIONS: In a large cohort of patients undergoing LT for alcoholic cirrhosis, a duration of abstinence of less than 6 months before wait-listing for LT, the presence of psychiatric comorbidities, or an HRAR score higher than 3 was associated with relapse into harmful drinking. The presence of more than 1 factor dramatically increased this risk over 50%. In the pre-LT evaluation in this setting, these factors should b
e accurately determined.

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Eur Surg Res. 2007 Aug 23;40(1):7-13 [Epub ahead of print]
Single-Center Experience on Liver Transplantation for Hepatocellular Carcinoma Arising in Alcoholic Cirrhosis: Results and Ethical Issues.
Sotiropoulos GC, Beckebaum S, Lang H, Frilling A, Molmenti EP, Cicinnati VR, Saner FH, Erim Y, Baba HA, Malagó M, Broelsch CE.
Department of General, Visceral, and Transplantation Surgery, University Hospital Essen, Essen, Germany.

Background: Liver transplantation is currently recognized as the optimal treatment for both early hepatocellular carcinoma in the setting of cirrhosis (HCC) as well as for alcoholic liver disease (ALD). The purpose of this study was to evaluate the outcome of patients with HCC and ALD in the absence of viral hepatitic infections. Methods: Twelve recipients were transplanted with a diagnosis of HCC and ALD in the absence of viral hepatitis during a 6-year period. Nine received deceased donor livers, and 3 live donor grafts. Our results were compared to those obtained by a search of the world literature. Results: The postoperative course was uneventful in all but one patient. All recipients experienced a good quality of life postoperatively. Three-year overall and recurrence-free survival rates were 82 and 73%, respectively. Nine patients are currently alive, after a median follow-up of 29 months. Conclusion: This is the first study to evaluate liver transplantation for HCC in ALD. Although outcomes are excellent, the evaluation of patients with ALD and HCC constitutes a challenging topic in transplantation surgery, especially when live liver donation is considered. An interdisciplinary structured approach is recommended, with special emphasis on ethical considerations. Copyright (c) 2008 S. Karger AG, Basel.

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J Hepatol. 2007 Aug;47(2):277-83. Epub 2007 May 4.
A randomized trial of antioxidant therapy alone or with corticosteroids in acute alcoholic hepatitis.
Stewart S, Prince M, Bassendine M, Hudson M, James O, Jones D, Record C, Day CP.
Liver Research Group, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

BACKGROUND/AIMS: Oxidative stress is putatively involved in the pathogenesis of alcohol-induced liver injury. This trial was devised to determine whether antioxidant therapy, alone or as an adjunct to corticosteroids, improved survival in patients with acute alcoholic hepatitis. METHODS: Patients with a severe alcoholic hepatitis were stratified by sex and steroid use, and then randomized. The active group received N-acetylcysteine for one week, and vitamins A-E, biotin, selenium, zinc, manganese, copper, magnesium, folic acid and Coenzyme Q daily for 6 months. The trial was double blinded and placebo controlled. The primary end-point was mortality within 6 months. RESULTS: Thirty-six (20 male, 16 female; mean discriminant function (DF) 86.6) received active drug, and 34 (18 male, 16 female; mean DF 76.4) received placebo. 180-day survival was not significantly different between patients receiving drug and placebo (52.8% vs. 55.8%, p=0.699). This was not affected by stratification for steroid use or sex. The only predictors of survival in multivariate analysis were initial bilirubin (p=0.017), white cell count (p=0.016) and age (p=0.037). Treatment allocation did not affect survival in multivariate analysis (p=0.830). CONCLUSIONS: Antioxidant therapy, alone or in combination with corticosteroids, does not improve 6-month survival in severe alcoholic hepatitis.

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Arch Intern Med. 2007 Jun 11;167(11):1183-8.
A simple score for predicting alcohol relapse after liver transplantation: results from 387 patients over 15 years.
De Gottardi A, Spahr L, Gelez P, Morard I, Mentha G, Guillaud O, Majno P, Morel P, Hadengue A, Paliard P, Scoazec JY, Boillot O, Giostra E, Dumortier J.
Divisions of Gastroenterology and Hepatology, University Hospital, Geneva, Switzerland.

BACKGROUND: Alcohol relapse can negatively influence the outcome after liver transplantation (LT). The aim of our study was to identify factors that could be associated with the recurrence of harmful alcohol consumption after LT. METHODS: A total of 387 consecutive patients (23.8% women) who underwent LT for alcoholic cirrhosis in Geneva, Switzerland, and Lyon, France, between 1989 and 2005 were evaluated. Mean +/- SD age was 51.3 +/- 7.5 years. Follow-up time was 61.2 +/- 47.5 months. Alcohol consumption relapse and potential factors associated with it were studied. RESULTS: The relapse rate of harmful alcohol consumption after LT was 11.9%. In univariate analysis, alcohol relapse was significantly associated with age greater than 50 years (P = .04), year of LT 1995 or earlier (P<.05), duration of abstinence less than 6 months (P = .02), presence of psychiatric comorbidities (P<.001), presence of a life partner (P<.05), and a high score on the High-Risk Alcoholism Relapse (HRAR) scale (P<.001). Multivariate logistic regression disclosed the following independent factors of relapse: duration of abstinence of less than 6 months (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.2-9.3) (P = .02); presence of psychiatric comorbidities (OR, 7.8; 95% CI, 3.1-20.0) (P<.001); and HRAR score higher than 3 (OR, 10.7; 95% CI, 3.8-30.0) (P = .001). In patients with none of these factors, alcohol relapse was 5%, while the presence of 1, 2, or 3 factors was associated with relapse rates of 18%, 64%, and 100% of the patients, respectively. CONCLUSIONS: In a large cohort of patients undergoing LT for alcoholic cirrhosis, a duration of abstinence of less than 6 months before wait-listing for LT, the presence of psychiatric comorbidities, or an HRAR score higher than 3 was associated with relapse into harmful drinking. The presence of more than 1 factor dramatically increased this risk over 50%. In the pre-LT evaluation in this setting, these factors should be accurately determined.

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Curr Opin Gastroenterol. 2007 May;23(3):292-8.
Liver transplantation: an update 2007.
Said A, Einstein M, Lucey MR.
aSection of Gastroenterology and Hepatology, USA bDepartment of Medicine, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, Wisconsin, USA.

PURPOSE OF REVIEW: Recent attention in liver transplantation has focused on equity in organ allocation and management of posttransplant complications. RECENT FINDINGS: Adoption of the model for end-stage liver disease for liver allocation has been successful in implementing a system based on medical urgency rather than waiting time. Refinements are being studied in improving the prediction of mortality and improving transplant benefit by balancing pretransplant mortality and posttransplant survival. Emerging literature is examining expansion of the current criteria for transplantation of hepatocellular carcinoma and the role of neoadjuvant therapy. Chronic renal dysfunction after liver transplantation is a source of considerable morbidity. Nephron-sparing immunosuppression regimens are emerging with encouraging results. Hepatitis C virus infection is difficult to differentiate histologically from rejection, although newer markers are being developed. Antiviral and immunosuppressive strategies for reducing the severity of hepatitis C virus recurrence are discussed. Alcohol relapse is common after liver transplant in alcoholic liver disease patients and can lead to worse outcomes. SUMMARY: Organ allocation tends to evolve under the model for end-stage liver disease with a focus on maximizing transplant benefit. Hepatitis C virus, hepatocellular carcinoma, chronic renal dysfunction and alcohol relapse are major challenges, and continued research in these areas will undoubtedly lead to better outcomes for transplant recipients.

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Curr Opin Gastroenterol. 2007 May;23(3):283-91.
Alcohol and the liver.
Reuben A.
Liver Service, Division of Gastroenterology and Hepatology, And Liver Transplant Program, Medical University of South Carolina, Charleston, South Carolina, USA.

PURPOSE OF REVIEW: This review aims to acquaint the reader with advances in 2006 in the epidemiology, genetics, detection, pathogenesis and treatment of alcoholic liver disease. RECENT FINDINGS: Important discoveries have been made in pathogenesis and mechanism of disease, with great emphasis on the many pathways leading to oxidative stress, and the novel mechanism of endoplasmic reticulum stress that is proving to be important in the pathogenesis of many liver diseases. The reliability of ethyl glucuronide and other biomarkers for the detection of alcohol abuse is being better established. There have been no treatment advances for alcoholic liver disease but, on balance, steroids are still favored for carefully selected patients with alcoholic hepatitis. Many compounds tested in rodents may now be available for consideration for clinical trials. Criteria for patient selection and refusal for liver transplantation are being established but the 6 months abstinence rule still holds. SUMMARY: Insights are being made into the pathogenesis of alcoholic liver disease but safe and effective therapies for both alcoholic hepatitis and alcoholic cirrhosis have yet to be discovered.

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Am J Gastroenterol. 2007 Feb 21; [Epub ahead of print]
Negative Impact of De Novo Malignancies Rather than Alcohol Relapse on Survival After Liver Transplantation for Alcoholic Cirrhosis: A Retrospective Analysis of 305 Patients in a Single Center.
Dumortier J, Guillaud O, Adham M, Boucaud C, Delafosse B, Bouffard Y, Paliard P, Scoazec JY, Boillot O.
Federation des Specialites Digestives, Hopital Edouard Herriot, Lyon, France.

OBJECTIVES: Alcoholic liver disease is a leading indication for liver transplantation (LT). The aim of this study was to evaluate long-term results and survival prognostic factors of LT in this indication from a large cohort of patients. METHODS: From October 1990 to October 2005, 305 consecutive patients with alcoholic cirrhosis (from 594 patients presenting with cirrhosis, i.e., 51.3%) underwent LT in our center. There were 229 men and 76 women, with a median age of 50 yr (range 30-68). Clinical and biological variables with possible prognostic value were analyzed. RESULTS: Global survival rate was 92.6% at 1 yr, 88.5% at 3 yr, 84.3% at 5 yr, and 73.4% at 10 yr, and was similar (P= 0.78, log-rank test) to that of patients transplanted for other cirrhosis (88.8% at 1 yr, 84.1% at 3 yr, 80.6% at 5 yr, and 74.7% at 10 yr). Recurrence of alcohol consumption was observed in 37 patients (12.1%). De novo cancer occurred in 35 patients after LT (11.5%). Univariate analysis disclosed that male gender, history of smoking, and de novo carcinoma were significant survival prognostic factors (P < 0.05, log-rank test). CONCLUSIONS: Our results strongly confirm that alcoholic liver disease is an excellent indication for LT, but long-term survival is reduced because of other target-organ damage of both alcohol and tobacco, especially aero-digestive malignancies, which are greater causes of morbidity and mortality than is recurrent alcohol liver disease.

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Liver Transpl. 2007 Jan 4;13(2):197-205 [Epub ahead of print]
Long-term survival and predictors of relapse after orthotopic liver transplantation for alcoholic liver disease.
Pfitzmann R, Schwenzer J, Rayes N, Seehofer D, Neuhaus R, Nussler NC.
Department of Surgery, Charite Campus Virchow-Klinikum, University Medicine Berlin, Berlin, Germany.

The relevance of sobriety for outcome after orthotopic liver transplantation (OLT) for alcoholic liver disease (ALD) is still discussed controversially. We conducted a retrospective analysis of 300 patients transplanted for ALD with regard to recurrent alcohol consumption, risk factors for drinking after OLT, and long-term survival. The 300 patients underwent OLT for ALD between 1989 and 2002. Median follow-up was 89 months. Incidence and severity of drinking, survival rates, and causes of death were assessed. Age, gender, duration of pretransplant sobriety, social support, presence of children, and the results of psychosomatic evaluation were analyzed for their impact on recurrent alcohol consumption after OLT. Drinking of various degrees was observed in 19% of ALD patients after OLT. Pretransplant sobriety of less than 6 months, absence of companion in life, presence of young children, and a predicted poor psychosomatic prognosis were associated with an increased risk of recurrent alcohol consumption, whereas age and gender were not independent risk factors. Survival rates of patients who resumed abusive drinking were significantly lower than survival rates of abstinent patients or patients with minor lapses. Recurrent alcoholic liver disease accounted for the vast majority of deaths among patients who resumed abusive drinking after OLT, whereas malignant tumors, infections, and cardiovascular disease were the most common causes of death among abstinent patients. In conclusion, abusive drinking after OLT is associated with poor long-term survival. Analysis of risk factors may help to identify patients with a high risk for recurrent alcohol abuse after OLT. Liver Transpl, 2006. (c) 2006 AASLD.

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Nat Clin Pract Gastroenterol Hepatol. 2007 Jan;4(1):24-34.
Management strategies in alcoholic liver disease.
Tilg H, Day CP.
Christian-Doppler Research Laboratory for Gut Inflammation and Department of Medicine, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. herbert.tilg@uibk.ac.at

Alcoholic liver disease (ALD) and its complications is still one of the most frequent causes of death in the Western world. Treatment modalities for both alcoholic steatohepatitis (ASH; the major inflammatory complication of ALD) and alcoholic liver cirrhosis are insufficient. Severe ASH is associated with a high mortality; although glucocorticoid treatment has been reported to improve survival, meta-analyses of clinical trials performed to date have failed to show a convincing benefit of such an approach. Most of the progress in understanding these diseases, especially ASH, has come from studies of cytokines. Various proinflammatory cytokines, such as tumor necrosis factor (TNF), have been proposed to have an important role in the pathophysiology of ALD and its complications. Pilot studies on the use of anti-TNF drugs, such as pentoxifylline or infliximab, in the treatment of ASH have now been performed with various levels of success. The treatment of patients with alcohol-related cirrhosis is mainly symptomatic and no therapies are currently available except orthotopic liver transplantation for end-stage liver disease. Independent of the stage of disease, abstinence from alcohol is the cornerstone of management. New treatment modalities for these diseases are eagerly awaited.

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Best Pract Res Clin Gastroenterol. 2007;21(1):175-90.
Indications of liver transplantation in patients with complications of cirrhosis.
Francoz C, Belghiti J, Durand F.
Service d'Hepatologie, INSERM, Bichat Beaujon, Clichy, France.

Transplantation is the only option for reversing liver insufficiency and its complications in patients with end-stage cirrhosis. Transplantation is generally considered after the first episode of decompensation of cirrhosis, provided no specific intervention can result in a longstanding return to the compensated state. Alcohol abuse and hepatitis C virus infection are the predominant causes leading to transplantation in Western countries. In cases of alcoholic cirrhosis, a 6-month period of abstinence is needed before transplantation. Patients with hepatitis C virus infection are considered independent of viral replication, even if post-transplantation recurrence is almost constant. Conversely, in cases of hepatitis B infection, only patients without viral replication (or with extremely low viral load) are suitable candidates. Hepatocellular carcinoma represents an increasing proportion of the indications and offers excellent long-term survival. However, transplantation should be limited to patients with small tumours. HIV infection no longer represents a definitive contraindication.

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Z Psychosom Med Psychother. 2006;52(4):341-57.
[Stabilisation of abstinence by means of psychoeducation for patients with alcoholic liver disease awaiting liver transplantation]
[Article in German]
Erim Y, Beckmann M, Tagay S, Beckebaum S, Gerken G, Broelsch CE, Senf W.
Klinik fur Psychosomatische Medizin und Psychotherapie der Universitat Duisburg-Essen. yesim.erim@uni-essen.de

BACKGROUND: A manualised six-month psychoeducational intervention was conducted in patients with alcoholic liver disease and abstinence problems who were waiting for a transplantation.OBJECTIVES: In a naturalistic design it was investigated whether the intervention could improve patients' alcohol abstinence. METHODS: Between January 2002 and November 2003, 72 patients were enrolled in the therapeutic intervention, 48 of whom participated in group therapy. Health-related quality of life (SF-12), anxiety and depression (HADS-D), symptom strain (BSI) and social support (F-SOZU) were measured. Alcohol abstinence was examined in each group session by measuring the alcohol concentration in breath. RESULTS: At the beginning and end of the group therapy patients showed subsyndromal measures of anxiety and depression and minor symptoms of psychopathology. Physical quality of life was reduced (t = -8.694; df = 44; p < .001). Mental quality of life was in the range of the normative sample and was correlated with depression (r = -0.400; p = .009). Patients perceived high social support (t = 8.213; df = 45; p < .001). During the course of therapy four patients had relapses but the remaining patients stayed abstinent. Physical quality of life improved (t = -2.275; df = 27; p = .031), mental quality of life and symptom strain remained stable. CONCLUSIONS: The therapy presented here facilitated a stabilisation of mental well-being in patients with alcoholic liver disease who were waiting for organ transplantation. The relapse rate measured by alcohol concentration in breath remained low.

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World J Gastroenterol. 2006 Nov 21;12(43):6909-21.
Current concepts and controversies in the treatment of alcoholic hepatitis.
Rongey C, Kaplowitz N.
Robert Wood Johnson Clinical Scholars Program, University of California at Los Angeles, 911 Broxton Avenue, Los Angeles, CA 90024, USA. crongey@mednet.ucla.edu

The treatment of alcoholic hepatitis remains one of the most debated topics in medicine and a field of continued research. In this review, we discuss the evolution of scoring systems, including the recent development of the Glasgow alcoholic hepatitis score, role of liver biopsy and current treatment interventions. Studies of treatment interventions with glucocorticoids, pentoxifylline, infliximab, s-adenosyl-methionine, and colchicine are reviewed with discussion on quality. Glucocorticoids currently remain the mainstay of treatment for severe alcoholic hepatitis.

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Cochrane Database Syst Rev. 2006 Oct 18;(4):CD003045. Update of:
Cochrane Database Syst Rev. 2003;(1):CD003045.
Anabolic-androgenic steroids for alcoholic liver disease.
Rambaldi A, Gluud C.
Centre for Clinical Intervention Research, Copenhagen Trial Unit, Department 7102, H:S Rigshospitalet, Blegdamsvej 9, Copenhagen University Hospital, Copenhagen, Denmark. arambaldi@hotmail.com

BACKGROUND: Alcohol is one of the most common causes of liver disease in the Western World. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease. OBJECTIVES: To assess the beneficial and harmful effects of anabolic-androgenic steroids for patients with alcoholic liver disease based on the results of randomised clinical trials. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Controlled Trials Register in The Cochrane Library, MEDLINE, EMBASE, LILACS, and Science Citation Index Expanded until June 2006. Electronic searches were combined with full text searches. Manufacturers and researchers in the field were also contacted. SELECTION CRITERIA: Randomised clinical trials studying patients with alcoholic steatosis, alcoholic fibrosis, alcoholic hepatitis, and/or alcoholic cirrhosis were included. Interventions encompassed anabolic-androgenic steroids at any dose or duration versus placebo or no intervention. The trials could be double blind, single blind, or unblinded. The trials could be unpublished or published, and no language limitations were applied. DATA COLLECTION AND ANALYSIS: Outcomes are assessed at maximal follow-up. All analyses were performed according to the intention-to-treat method. The statistical package RevMan Analyses was used. The methodological quality of the randomised clinical trials was assessed. MAIN RESULTS: Combining the results of five randomised clinical trials randomising 499 patients with alcoholic hepatitis and/or cirrhosis demonstrated no significant effects of anabolic-androgenic steroids on mortality (relative risk (RR) 1.01, 95% confidence interval (CI) 0.79 to 1.29), liver-related mortality (RR 0.83, 95% CI 0.60 to 1.15), complications of liver disease (RR 1.25, 95% CI 0.74 to 2.10), and liver histology. Anabolic-androgenic steroids did not significantly affect a number of other outcome measures, including sexual function and liver biochemistry. Anabolic-androgenic steroids were not associated with a significantly increased risk of non-serious adverse events (RR 1.14, 95% CI 0.50 to 2.59) or with serious adverse events (RR 4.54, 95% CI 0.57 to 36.30). AUTHORS' CONCLUSIONS: This systematic review could not demonstrate any significant beneficial effects of anabolic-androgenic steroids on any clinically important outcomes (mortality, liver-related mortality, liver complications, and histology) of patients with alcoholic liver disease.
  
Previous Research on Alcoholic Liver Disease:
2002-2006   
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