What are the diagnostic criteria and treatment options for a patient with a history of heavy alcohol use suspected of having alcoholic hepatitis?

Diagnostic Criteria for Alcoholic Hepatitis

Alcoholic hepatitis is primarily a clinical diagnosis requiring three core elements: heavy alcohol use (typically >80 g/day) within the past 60 days, rapid onset of jaundice (bilirubin >3 mg/dL), and characteristic laboratory findings including AST >50 IU/mL but rarely >400 IU/mL with an AST/ALT ratio >1.5-2.0. 1, 2

Essential Diagnostic Components

Alcohol History

• Document detailed consumption history including amount, frequency, duration, and pattern of drinking as the foundation of diagnosis 1
• Heavy alcohol use is generally defined as >80 g/day, though no absolute threshold exists 1
• Recent alcohol use within the past 60 days is required for diagnosis 2
• Use direct biomarkers to confirm consumption: urine ethyl glucuronide (uETG) detects use for 3-4 days, while 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

Clinical Presentation

• Rapid onset of jaundice is the cardinal feature with serum bilirubin typically >3 mg/dL 2
• Tender hepatomegaly on physical examination is commonly present 2, 3
• Fever may occur even without infection 2
• Hepatic decompensation including ascites, encephalopathy, bacterial infection, or variceal bleeding frequently accompanies the presentation 2
• Anorexia, weight loss, and fatigue are common early signs 3

Laboratory Pattern Recognition

The characteristic laboratory pattern is highly specific:

• AST elevation >50 IU/mL but rarely exceeding 300-400 IU/mL 1, 2
• AST/ALT ratio >1.5-2.0 (ratios <1.5 seen in <2% of histologically proven cases) 1, 2
• Elevated bilirubin >3 mg/dL 2
• Neutrophilia is frequently present 1, 2
• Prolonged prothrombin time/INR 1
• Hypoalbuminemia 1
• Thrombocytopenia 1

Important caveat: An AST/ALT ratio >2 is highly suggestive of alcoholic liver disease, but a ratio <1.5 represents atypical laboratory findings requiring liver biopsy for confirmation 4

NIAAA Diagnostic Classification System

The National Institute on Alcohol Abuse and Alcoholism provides a three-tier diagnostic framework 1, 4:

Definite Alcoholic Hepatitis

• Clinical diagnosis plus liver biopsy confirmation 2
• Histology requires macrovesicular steatosis plus at least one of: neutrophil infiltration, hepatocyte ballooning, or Mallory-Denk bodies 2

Probable Alcoholic Hepatitis

• Heavy alcohol use within 60 days 4
• Typical liver tests without confounding factors 4
• In such cases <10% will have an alternative diagnosis on biopsy 4
• This classification carries acceptable diagnostic accuracy for clinical management 4

Possible Alcoholic Hepatitis

• Cases with AST <50 IU/mL or atypical laboratory findings 4
• Liver biopsy is required for confirmation because the risk of misdiagnosis is high 4

Critical pitfall: Studies show that histologic confirmation is only present in 70-80% of patients with clinically presumed acute alcoholic hepatitis, meaning clinical diagnosis alone carries a 10-50% risk of misclassification 5, 2

Exclusion of Alternative Diagnoses

Before confirming alcoholic hepatitis, systematically exclude:

• Biliary obstruction via imaging (ultrasound, CT, or MRI) 5, 1, 2
• Viral hepatitis (HBV, HCV) 5, 2
• Severe autoimmune liver disease 2
• Wilson disease 2
• Drug-induced liver injury 5
• Hepatocellular carcinoma 5

Imaging findings typically show: fatty liver, hepatomegaly, and ascites in severe cases, but imaging alone cannot diagnose alcoholic hepatitis 1

Role of Liver Biopsy

Liver biopsy is not necessary for routine diagnosis but should be strongly considered in specific scenarios 5, 2:

• Atypical presentation or history 2
• Confounding factors present 2
• When aggressive treatment with significant risk is contemplated 2
• AST <50 IU/mL or AST/ALT ratio <1.5 4

The transjugular approach is preferred due to frequent coagulopathy and ascites in these patients 2

Around 20% of alcohol abusers with abnormal liver function tests have etiologies other than alcohol, and only 70% of patients with suspected severe alcoholic hepatitis are definitively diagnosed with alcoholic hepatitis using liver biopsy 5

Severity Assessment and Prognostic Scoring

Once diagnosis is established, calculate prognostic scores to identify severe disease:

Maddrey Discriminant Function (mDF)

• mDF ≥32 defines severe alcoholic hepatitis requiring treatment consideration 5, 1, 2
• Associated with 30-50% 28-day mortality without treatment 1
• Formula: 4.6 × (patient's PT - control PT) + serum bilirubin (mg/dL) 6

MELD Score

• MELD >20-21 indicates severe disease with high 90-day mortality 1, 2
• Some guidelines suggest MELD >20 as an alternative threshold for treatment eligibility 5

Lille Score

• Calculated on day 7 of corticosteroid treatment 5, 2
• Lille score ≥0.45 indicates non-responders who should discontinue steroids 5, 6
• Lille score <0.45 predicts benefit from completing 28-day steroid course 5

Additional Prognostic Models

• ABIC score (Age, Bilirubin, INR, Creatinine) 7
• Glasgow Alcoholic Hepatitis Score 7
• CLIF-C OFS (Consortium Organ Failure Score) for acute-on-chronic liver failure 2
• Alcoholic Hepatitis Histologic Score (AHHS) if biopsy performed, though limited by interobserver variability 5, 7

Special Considerations in Cirrhotic Patients

• Patients with undiagnosed or known cirrhosis may decompensate due to superimposed alcoholic hepatitis, presenting as acute-on-chronic liver failure 2
• Identify underlying cirrhosis through imaging findings: liver dysmorphy, portal-systemic collaterals, splenomegaly, caudate lobe hypertrophy, posterior hepatic notch visualization 2
• Asymptomatic histologic alcoholic steatohepatitis may coexist with cirrhosis in 30-40% of patients 2
• Clinical stigmata and laboratory markers including thrombocytopenia, hypoalbuminemia, and prolonged INR suggest underlying cirrhosis 2

Treatment Eligibility Assessment

For patients with mDF ≥32 or MELD >20, proceed with treatment eligibility screening 5:

Screen for Contraindications

• Uncontrolled infections (obtain chest x-ray, blood, urine, and ascites cultures) 5
• Acute kidney injury with serum creatinine >2.5 mg/dL 5
• Uncontrolled upper gastrointestinal bleeding 5
• Concomitant diseases including HBV, HCV, drug-induced liver injury, hepatocellular carcinoma, acute pancreatitis, HIV, tuberculosis 5
• Multiorgan failure or shock 5

If Eligible for Treatment

• Start prednisolone 40 mg daily or equivalent with or without IV N-acetylcysteine 5
• Implement enteral nutrition goal of >21 kcal/kg (or 30-40 kcal/kg/day with 1.0-1.5 g protein/kg/day) 5, 4
• Consider referral for early liver transplantation or palliative care as clinically appropriate 5

Monitoring Response

• Calculate Lille score on day 7 5
• If Lille <0.45, continue prednisolone for 28 days total 5
• If Lille ≥0.45, discontinue steroids as patient is a non-responder 5
• Support life-long abstinence from alcohol 5

Management for Non-Severe Disease

For patients not meeting severe criteria (mDF <32 and MELD ≤20):

• Alcohol abstinence is the single most effective intervention for long-term survival 5, 4
• Abstinence can result in normalization of liver enzymes and improved clinical features even in cirrhosis 5, 4
• Initiate abstinence counseling immediately 4
• Thiamine supplementation to prevent Wernicke's encephalopathy 4
• Aggressive nutritional support with 1.0-1.5 g protein/kg/day and 30-40 kcal/kg/day 4