What is the diagnostic approach for an adult patient with a history of chronic alcohol abuse suspected to have alcohol-related hepatitis?

Diagnostic Approach to Alcoholic Hepatitis

The diagnosis of alcoholic hepatitis is primarily clinical, based on a detailed alcohol history, characteristic laboratory findings (AST/ALT ratio >1.5-2.0, AST typically 50-300 IU/L, bilirubin >50 μmol/L), and recent onset of jaundice in a patient with chronic heavy alcohol use (typically >80 g/day for decades). 1

Essential Clinical Criteria

Obtain a thorough alcohol consumption history documenting the amount (grams per day), frequency, duration (typically decades), and pattern of drinking—this is the foundation of diagnosis. 1 Heavy alcohol use is generally defined as >80 g/day, though no absolute threshold exists. 1

Cardinal clinical features to identify:

• Progressive jaundice (the hallmark sign) with recent onset 1
• Fever (even without infection) 1
• Tender hepatomegaly 1
• Malaise, weight loss, and malnutrition 1
• Ascites and/or hepatic encephalopathy in severe cases 1

Laboratory Pattern Recognition

Characteristic laboratory findings include: 1, 2

• AST/ALT ratio >1.5-2.0 (ratios >2 are highly suggestive, >3 even more specific) 1, 2
• AST elevation >50 IU/ml but rarely >300 IU/ml 1
• Hyperbilirubinemia >50 μmol/L 1
• Neutrophilia (leukocytosis) 1
• Prolonged prothrombin time/INR 1
• Hypoalbuminemia 1
• Thrombocytopenia 1

Critical caveat: AST levels <50 IU/ml or >400 IU/ml, or AST/ALT ratio <1.5 represent atypical findings that should raise suspicion for alternative diagnoses. 1, 3

NIAAA Diagnostic Classification System

Apply the NIAAA three-tier diagnostic framework: 1, 3

• Definite AH: Clinically diagnosed AND biopsy-proven 1
• Probable AH: Heavy alcohol use + typical laboratory tests without confounding factors (misdiagnosis risk <10% on biopsy) 1, 3
• Possible AH: Atypical features including uncertain alcohol assessment, AST <50 or >400 IU/ml, AST/ALT <1.5, or potential confounding factors (high misdiagnosis risk—biopsy essential) 1, 3

Mandatory Exclusions Before Diagnosis

Screen for competing diagnoses that can mimic alcoholic hepatitis: 1

• Viral hepatitis: Test HBsAg, anti-HBc, anti-HCV with reflex HCV RNA, HAV IgM, HEV serology 1
• Drug-induced liver injury: Detailed medication history including over-the-counter drugs, herbals, and supplements 1
• Sepsis and bacterial infections 1
• Gallstone disease/biliary obstruction 1
• Ischemic hepatitis 1

Important pitfall: Up to 10-20% of clinically suspected alcoholic hepatitis cases have alternative diagnoses on liver biopsy. 1

Role of Liver Biopsy

Liver biopsy via transjugular route should be performed in: 1

• Cases classified as "possible AH" with atypical features 1, 3
• Diagnostic uncertainty or suspected coexisting liver disease 1
• Patients being considered for corticosteroid therapy where confirmation would change management 1
• When prognostic information is needed 1

Transjugular approach is mandatory due to frequent coagulopathy and ascites in these patients. 1

Histological features confirming alcoholic hepatitis: 1

• Steatosis 1
• Hepatocellular ballooning 1
• Polymorphonuclear neutrophil infiltration 1
• Mallory-Denk bodies 1
• Perisinusoidal fibrosis 1

Biopsy is NOT required in cases of "probable AH" where clinical and laboratory criteria are typical and no confounding factors exist—the misdiagnosis risk is acceptably low (<10%). 1

Severity Assessment

Calculate prognostic scores to identify severe disease: 1

• Maddrey Discriminant Function (mDF): Score ≥32 defines severe alcoholic hepatitis with 30-50% 28-day mortality without treatment 1
• MELD score: Threshold of 17-20 indicates severe disease 1
• Glasgow Alcoholic Hepatitis Score (GAHS) and ABIC score are alternative options 1

Critical terminology update: Avoid calling alcoholic hepatitis with mDF <32 "non-severe"—these patients still have approximately 10% mortality at 6 months and 20% at 1 year. 1

Alcohol Consumption Monitoring

Document abstinence using direct biomarkers: 1

• Urine ethyl glucuronide (uETG): Detects alcohol use for 3-4 days 1
• Hair ethyl glucuronide (hEtG): Detects chronic excessive consumption with cut-offs: <7 pg/mg (abstinence), 7-30 pg/mg (social drinking), >30 pg/mg (chronic excessive use >60 g/day) 1

Imaging Studies

Imaging (ultrasound, CT, or MRI) typically shows: 1

• Fatty liver 1
• Hepatomegaly 1
• Ascites in severe cases 1
• Features of cirrhosis if present (nodular surface, splenomegaly, varices) 1

Imaging alone cannot diagnose alcoholic hepatitis but helps exclude biliary obstruction and assess for cirrhosis. 1

Common Diagnostic Pitfalls

• Normal liver enzymes do not exclude significant alcohol-related liver disease. 2
• Patients may have ceased drinking days to weeks before symptom onset—this does not exclude the diagnosis. 1
• Coexisting liver disease etiologies occur in up to 20% of cases—always screen for viral hepatitis and other causes. 1, 2
• AST/ALT ratio becomes less specific in established cirrhosis. 2
• The absence of jaundice suggests alcoholic fatty liver rather than alcoholic hepatitis. 3