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

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

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

Laboratory Finding albumin 2.5 (3.5-5.2 g/dL) AST 185 (10-59U/L) ALT 50 (13-40U/L) Alk phos 90 (53-128 IU/L) amylase 150 (27-131 U/L) lipase 230 (12-70 U/L) Ascites: albumin <1, 150 WBC (10% segs) RUQ U/S: large ascites, nodular liver, mild splenomegaly 4

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

Alcoholic Liver Disease-Spectrum

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)

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)

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

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

Histology

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

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

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