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Welcome to the Alcoholic
Liver Disease File
Patients all over the world
have used the information in The Alcoholic Liver Disease File
since 1992, when the Center for Current Researchone of
the first 80 companies on the Internetwas founded. Our
highly trained researchers (all of whom hold Ph.D.s) have searched
the advanced medical database at the National Library of Medicine
and compiled a comprehensive collection of research descriptions
on Alcoholic Liver Disease and its care.
As you will see, the following research descriptions detail the
findings published in the most respected journals in the field.
Because the research descriptions are written in medical terms,
most people will bring all or parts of the Alcoholic Liver Disease
File to their doctor for further explanation and discussion.
Often your doctor will have access to full-text articles and
other information that could be useful in planning a successful
course of treatment and prevention. Note that the titles of the
journals are abbreviated according to the National Library of
Medicine's format; your doctor can provide the full title if
you need it.
Thank you for accessing the Alcoholic Liver Disease File. We
truly hope the information fosters better health.
Sincerely,
Gregory A. Fraser, Ph.D.
Director of ResearchImportant 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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Latest Research on
Alcoholic Liver Disease
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.
-----
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.
-----
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.
-----
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.
-----
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.
-----
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.
-----
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.
-----
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.
-----
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.
-----
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.
-----
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.
-----
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.
-----
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.
-----
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.
-----
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.
-----
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.
-----
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.
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