1. Clinical Case Alcoholic Liver disease Prepared By: Tasnim Kullab
Haneen Akella
Abeer Jendia

2. 50 M with no PMH admitted with 1 week h/o
jaundice, abdominal pain and distention; also
with increasing fatigue.
+ h/o chronic alcohol abuse, attempted AA without success
Recent alcohol binging over the past 2 months especially on weekends-drinks a fifth of whiskey/day

3. Clinical Case None None Single businessman NKDA
Medications:
None
Social History:
Single businessman
+ ETOH-multiple attempts at rehab
No IVDU
No tobacco
PMH/PSH:
None
Allergies:
NKDA
FH:
No FH of liver disease 3

4. Laboratory Finding albumin 2.5 (3.5-5.2 g/dL) AST 185 (10-59U/L)
ALT (13-40U/L)
Alk phos ( IU/L)
amylase ( U/L)
lipase (12-70 U/L)
Ascites: albumin <1, 150 WBC (10% segs)
RUQ U/S: large ascites, nodular liver, mild splenomegaly 4

5. Alcoholic Liver Disease
Affects 1% of the US Population
Ranges from simple steatosis, alcoholic hepatitis, to cirrhosis
Accounts for >12000 deaths/yr
2nd most frequent indication for OLT

6. Alcoholic Liver Disease-Spectrum

7. Alcoholic Hepatitis
Clinical syndrome of jaundice and liver failure, generally with chronic alcohol use (mean ~100 gm/day)
Common symptoms apart from jaundice include fever, ascites, cachexia, RUQ pain and HE
Risk factors include amount of alcohol ingested (not a linear relationship); increased risk with female sex
Genetic factors (increased risk in children of alcoholics)
Protein calorie malnutrition
Concomitant viral hepatitis (HCV)

8. Pathogenesis
Oxidative metabolism to acetaldehyde generates reactive oxygen species, which induce lipid peroxidation, causing hepatocellular death via necrosis/apoptosis
Increased endotoxin levels due to intestinal permeability leading to increased pro-inflammatory cytokines by activating Kupffer cells (TNF α levels are higher in pts with AH than in pts with inactive cirrhosis)

9. Lucey M et al. N Engl J Med 2009;360:2758-2769

10. Diagnosis Elevated AST and ALT ( rarely > 300 IU/ml)
AST/ALT > 2:1
Increased GGT -independent of liver disease
Leukocytosis with neutrophilia
Increased MCV (80-100% pts) –due to ETOH induced marrow toxicity, B12/folate deficiency
Elevated creatinine-ominous sign (HRS)
Carbohydrate deficient transferrin
Elevated IgA levels
Hyperbilirubinemia, coagulopathy, TCP

11. Histology

12. Assessing Illness Severity
Maddrey’s Discriminant Function
MELD
Glasgow Alcoholic Hepatitis Score
ECBL
Lille model

13. Therapy-Corticosteroids
Most intensely studied yet most hotly debated
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 CONTRAINDICATIONS:
-Infection/sepsis
-GI bleed
-Renal insufficiency

14. Liver Transplantation
AH is considered a contraindication to transplantation and 6 months of abstinence is recommended as minimal listing criterion although small studies have shown no worse outcomes in pts with AH
Recidivism rates range from 11-50% at 3-5 years post-transplantation