barcelona . spain - European Association for the Study of the Liver

BARCELONA . SPAIN
102 POSTGRADUATE COURSE SYLLABUS ALCOHOLIC LIVER DISEASE 103
APRIL 18 - 19/2012 THE INTERNATIONAL LIVER CONGRESS TM 2012
Jepsen P, Ott P, Andersen PK, Sørensen HT, Vilstrup H. Clinical course of alcoholic liver
cirrhosis: a Danish population-based cohort study. Hepatology. 2010;51(5):1675-82.
Baňares R, Nevens F, Larsen FS, Jalan R, Albillos A, Dollinger M. Extracorporeal liver support
with the molecular adsorbent recirculating system (MARS) in patients with acute-on-chronic
liver failure The RELIEF Trial. J Heptatol. 2010;52 (Suppl 1): S459-60.
Rifai K, Kribben A, Gerken G, hag S, herget-Rosenthal S, Treichel U, Betz C, Sarrazin C,
Van Vlierberghe H, Hoste E, Escorsell A, Ginès P, Hafer C, Schuchmann M, Galle PR,
Bernardi M, Caraceni P, Abeles D, Berr F, Knotek M, Kozik-Jaromin J, for the HELIOS Study
Group. Extracorporeal liver support by fractionated plasma separation and adsorption
(prometheus) in patients with acute-on-chronic liver failure (HELIOS study) :
a prospective randomized controlled multicenter study. J Hepatol. 2010; 52 (Suppl. 1):S3.
Lucey MR, Mathurin P, Morgan TR. Alcoholic hepatitis. N Engl J Med. 2009;360(26):2758-69.
Dunn W, Jamil LH, Brown LS, Wiesner RH Kim WR, Menon KV, Malinchoc M, Kamath P,
Shah V. MELD accuratelypPredicts mortality in patients with alcoholic hepatitis.
Hepatology 2005;41:353-8.
Srikureja W, Kyulo NL, Runyon BA, Hu Ke- Qin. MELD score is a better prognostic
model than Child-Turcotte-Pugh score or discriminant function score in patients with
alcoholic hepatitis. J Hepatol 2005;42:700-6.
Maddrey WC, Boitnott JK, Bedine MS, Weber FL, Mezey E, White RI. Corticosteroid therapy
of alcoholic hepatitis. Gastroenterology. 1978; 75:193-9
Mathurin P, O’Grady J, Carithers RL, Phillips M, Louvet A, Mendenhall CL, Ramond MJ,
Naveau S, Maddrey WC, Morgan TR. Corticosteroids improve short-term survival in patients
with severe alcoholic hepatitis: meta-analysis of individual patient data. Gut. 2011;60(2):255-60.
Louvet A, Naveau S, Abdelnour M, Ramond MJ, Diaz E, Fartoux L, Dharancy S,
Texier F, Hollebecque A, Serfaty L, Boleslawski E, Deltenre P, Canva V, Pruvot FR,
Mathurin P. The Lille model: a new tool for therapeutic strategy in patients with severe
alcoholic hepatitis treated with steroids. Hepatology. 2007;45(6):1348-54.
Forrest EH, Morris AJ, Stewart S, Phillips M, Oo YH, Fisher NC, Haydon G, O’Grady J,
Day CP. The Glasgow alcoholic hepatitis score identifies patients who may benefit
from corticosteroids. Gut. 2007;56(12):1743-6.
Dominguez M, Rincón D, Abraldes JG, Miquel R, Colmenero J, Bellot P, García-Pagán
JC, Fernández R, Moreno M, Bañares R, Arroyo V, Caballería J, Ginès P, Bataller R.
A new scoring system for prognostic stratification of patients with alcoholic hepatitis.
Am J Gastroenterol. 2008;103(11):2747-56.
Louvet A, Wartel F, Castel H, Dharancy S, Hollebecque A, Canva-Delcambre V, Deltenre P,
Mathurin P. Infection in patients with severe alcoholic hepatitis treated with steroids:
early response to therapy is the key factor. Gastroenterology. 2009;137(2):541-8.
Mathurin P, Duchatelle V, Ramond MJ, Degott C, Bedossa P, Erlinger S, Benhamou JP,
Chaput JC, Rueff B, Poynard T. Survival and prognostic factors in patients with severe
alcoholic hepatitis treated with prednisolone. Gastroenterology. 1996;110(6):1847-53.
Rajiv Jalan, Rajeshwar Prosad Mookerjee. Acute-on-chronic liver failure: an early
biopsy is essential Gut. 2010; 59(11):1455-6.
ALCOHOLIC STEATOHEPATITIS (ASH)
Antoine Hadengue
Geneva, Switzerland
E-mail: antoine.hadengue@gmail.com
KEY POINTS
• Alcoholic hepatitis is the clinical syndrome of jaundice or abnormal liver function tests in
alcohol abusers. Because decompensation in ALD can result from alcoholic steato-hepatitis
(ASH), infection, or other causes, ASH should be confirmed by liver biopsy.
• Alcoholic steatohepatitis (ASH) is defined at liver biopsy by the coexistence of steatosis,
hepatocyte ballooning and an inflammatory infiltrate with PMNs.
• Alcohol abstinence is the chief, vital objective in all forms of ASH, and deserves full
multidisciplinary investment.
• Severe ASH at risk of early death should be identified by one of the available scoring systems
before considering specific therapy.
• First-line therapy in patients with severe ASH includes corticosteroids. Early non-response
to steroids should be identified and stopping rules should be considered when steroids are
contraindicated, for example in case of ongoing sepsis, pentoxifylline should be used. However,
pentoxifyllin is not useful in combination with- or in non-responders to steroids.
• N-acetylcysteine, combined to corticosteroids in patients with severe ASH, has brought survival
benefit in one study and can be considered, especially in patients with poor nutritionnal status.
• Renal function and infection have a major impact on survival and should be closely monitored
in patients with severe ASH.
• Early liver transplantation may only be considered in highly selected patients with a first episode
of severe ASH, a favorable addiction profile and not responding to medical therapy.
DEFINITION AND INCIDENCE
The clinical syndrome of jaundice or abnormal liver function tests in alcohol abusers is called “alcoholic
hepatitis”. Historically, it has also been referred to as “acute alcoholic hepatitis”. Although the clinical
presentation may be abrupt, this is probably a misnomer, since alcoholic hepatitis is usually associated
with extensive fibrosis or cirrhosis and often follows a protracted course, weeks after alcohol abstinence.
The clinical syndrome of alcoholic hepatitis, often with ALD decompensation in non-abstinent patients,
opens a differential diagnosis where alcoholic steatohepatitis (ASH) is the leading, but not the only cause.
Other causes of ALD decompensation besides ASH, including infection, extensive microvesicular steatosis,
or superimposed drug-induced liver injury, will not be covered here. ASH is defined at histology by the
coexistence of steatosis, hepatocyte ballooning and an inflammatory infiltrate with PMNs. Uncertainty about
the exact cause of the syndrome may not be an issue in non-severe forms, when no specific therapy is
required. In severe forms however, where specific therapy with a potential for side-effects is considered,
ASH should be confirmed by histology.
Based on clinical diagnosis codes from a Danish registry the incidence of alcoholic hepatitis was estimated
to range from 24 to 46 per million in women and men, respectively [1]. In the United States, a clinical
diagnosis of alcoholic hepatitis accounted for 0.7 % of all hospital admissions in 2007 [2].
Because of the uncertainties behind a clinical diagnosis of “alcoholic hepatitis” and the limited number
of studies with a liver biopsy to ascertain a diagnosis of ASH, the true incidence and prevalence of ASH
in alcohol abusers is difficult to determine. Relying only on clinical criteria for the diagnosis of alcoholic
hepatitis entails a 10-50% risk of misclassifying patients with or without ASH. This has been established in
older studies [3, 4] and verified recently [5, 6]. Early liver biopsy (within 7 days) in 68 patients admitted for