Paul Y. Kwo, MD, FACG
Alcoholic Hepatitis Paul Y. Kwo, MD P f Professor off Medicine M di i Medical Director, Liver Transplantation Gastroenterology/Hepatology Division Indiana University School of Medicine 975 W. Walnut, IB 327 Indianapolis, IN 46202-5121 phone 317-274-3090 317 274 3090 fax 317-274-3106 email
[email protected]
Alcoholic Liver Disease • A major cause of morbidity and mortality in the United States • Encompasses a clinico-histological spectrum including - Fatty liver (hepatic steatosis) : present in 90% of heavy drinkers, rapidly reversible with abstinence - Alcoholic hepatitis occurs in 10-35% of heavy drinkers, precursor of cirrhosis - Alcoholic cirrhosis Hepatocellular cancer • Majority of people who abuse alcohol do not develop advanced lesions of alcoholic liver disease - 10-35% develop alcoholic hepatitis and/or cirrhosis
ACG Western Regional Postgraduate Course - Las Vegas, NV Copyright 2015 American College of Gastroenterology
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Paul Y. Kwo, MD, FACG
Alcohol • One standard drink •180 ml or 6 ounces of wine •360 ml or 12 ounces of beer •45 ml or 1.5 ounces of 90 proof –all contain ~12 grams of alcohol
•Threshold for Alcoholic Liver Disease –50-60 g alcohol/day for men, > 20 g/day for women –Low risk for alcoholic cirrhosis even at this level of consumption (4.2-5.9% in Italy, Denmark)
Liver Damage from Alcohol Excess Common, usually asymptomatic
Fatty Liver
Acute Alcoholic Hepatitis
Cirrhosis
ACG Western Regional Postgraduate Course - Las Vegas, NV Copyright 2015 American College of Gastroenterology
Variable severity. Typical hepatic inflammation Jaundice acute liver failure
Compensated or decompensated with portal hypertension/ encephalopathy/ ascites
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Paul Y. Kwo, MD, FACG
Alcoholic steatosis
Alcoholic Hepatitis with Mallory Hyaline and neutrophilic infiltrate
Mallory Body
Abnormal laboratory tests seen with excess alcohol consumption >
> >
>
ACG Western Regional Postgraduate Course - Las Vegas, NV Copyright 2015 American College of Gastroenterology
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Paul Y. Kwo, MD, FACG
Alcohol Metabolism Pathway: ADH and Alcohol Metabolism Microsomal (CYP 450) Pathways
Multiple pathogenic mechanisms lead to liver damage
ACG Western Regional Postgraduate Course - Las Vegas, NV Copyright 2015 American College of Gastroenterology
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Paul Y. Kwo, MD, FACG
Assessing Illness Severity some rely on response to therapy to predict prognosis Maddrey’s Discriminant Function Lille model: • incorporates response to steroids
MELD Score Glasgow Alcoholic Hepatitis Score ECBL (early change in bilirubin levels): • incorporates response to steroids
Maddrey’s Discriminant Function Most commonly used predictive model; developed to facilitate assessment of response to steroids t id in i 1978; 1978 modified difi d in i 1989
Discriminant function : (4.6 x [PT -control PT]) + (serum bilirubin) A DF ≥ 32 in the presence of HE predicts > 50% mortality at 28 days (in the absence of therapy); one month survival > 90% if DF < 32 Ramond MJ et al. N Engl J Med 1992;326:507-512.
ACG Western Regional Postgraduate Course - Las Vegas, NV Copyright 2015 American College of Gastroenterology
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Paul Y. Kwo, MD, FACG
Lille Model Six variables used to identify patients with severe AH (DF ≥ 32) not responding to steroids Lille score calculated after 7 days of steroids: 3.19–0.101×Age (years) +0.147×Albumin on day 0 (g/L) +0.0165×Evolution in bilirubin level (μmol/L) −0.206× Renal insufficiency −0.0065× Bilirubin on day 0 (μmol/L) −0.0096×PT (seconds) http://www.lillemodel.com/
Score ≥ 0.45 associated with marked decrease in 6 month survival (25% ( % vs 85%) %) Superior to CTP, DF, GAHS, and MELD at predicting prognosis Louvet A et al. Hepatology 2007;45:1348-54
Lille Model
Louvet A et al. Hepatology 2007;45:1348-54
ACG Western Regional Postgraduate Course - Las Vegas, NV Copyright 2015 American College of Gastroenterology
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Paul Y. Kwo, MD, FACG
MELD Score MELD derived to predict 3 month survival in cirrhosis patients 2 studies demonstrate prognostic benefit in alcoholic hepatitis MELD score >11 comparable to DF >32; although studies have suggested MELD cutoffs of 18, 19 and 21 for predicting prognosis MELD score on admission ≥ 18, MELD at 1 week ≥ 20 or rise in MELD ≥ 2 have been shown in a retrospective study to be more sensitive (91%) and specific (85%) than DF or CTP score in predicting mortality Dunn W et al. Hepatology 2005;41:353-8 Srikureja W et al. J Hepatol 2005;42:700-6
Medical Therapies
Abstinence Steroids Pentoxifylline Control craving Address Nutritional Needs Antinflammatory ? Antioxidant
ACG Western Regional Postgraduate Course - Las Vegas, NV Copyright 2015 American College of Gastroenterology
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Paul Y. Kwo, MD, FACG
Therapy-Corticosteroids Block cytotoxic as well as inflammatory pathways (inhibit NF-KB, decrease TNF α levels) Decrease intracellular adhesion molecule 1 in sinusoidal cells-inhibit leukocyte activation Prednisolone 40mg daily recommended in pts with DF ≥ 32 or HE for 28 day course +/- taper 2-3 weeks (guided by Lille score < 0.45) CONTRAINDICATIONS: -Infection/sepsis
-GI bleed -Renal insufficiency
Prednisolone for Severe Alcoholic Hepatitis 100 Corticosteroids
Survival (%)
50 Placebo
0 90
180
Day Ramond, 1992
ACG Western Regional Postgraduate Course - Las Vegas, NV Copyright 2015 American College of Gastroenterology
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Paul Y. Kwo, MD, FACG
Corticosteroids Improve 28-Day Survival in Patients with Severe Alcoholic Hepatitis: Individual Data Analysis of the Last 5 Randomized Controlled Trials Entry: DF > 32 # Patients 28-day Survival
Survival
C
202
79.2 ± 2.9%
NC
185
64.1 ± 3.5%
Univariate Analysis of Predictive Factors: C Age Creatinine Encephalopathy
p=0.0005
p=0.0005 p