Gastroenterology · Hepatology
The facts most likely to be tested
Press 1–5 to rate · ↑↓ to navigate
Alcohol-associated hepatitis is characterized by an AST:ALT ratio of 2:1 or greater, with absolute values of both enzymes typically less than 500 IU/L.
Mallory-Denk bodies (damaged intermediate filaments) are a characteristic histologic finding on liver biopsy in alcohol-associated liver disease, though they are not specific (also seen in MASH, Wilson disease, and primary biliary cholangitis).
The Maddrey Discriminant Function (MDF) score is used to determine the severity of alcohol-associated hepatitis and the necessity for corticosteroid therapy.
Pentoxifylline is no longer recommended for severe alcohol-associated hepatitis (AASLD 2019; ACG 2024), including in patients who have contraindications to corticosteroids.
Patients with alcohol-associated liver disease frequently present with macrocytosis (elevated MCV) due to the direct toxic effect of ethanol on the bone marrow.
Alcohol-associated cirrhosis is the end-stage result of chronic injury, characterized by irreversible fibrosis and the development of portal hypertension.
Abstinence from alcohol is the single most important factor in improving long-term survival and preventing disease progression at every stage of alcohol-associated liver disease.
Vignette unlocked
A 52-year-old male with a long history of heavy alcohol use presents with jaundice, right upper quadrant pain, and fever. Physical examination reveals hepatomegaly, ascites, and spider angiomata. Laboratory studies show an AST of 320 IU/L and an ALT of 140 IU/L. His Maddrey Discriminant Function score is 42.
What is the most appropriate initial pharmacologic treatment for this patient?
Prednisolone
The patient has severe alcohol-associated hepatitis (formerly alcoholic hepatitis; MDF > 32), which is an indication for corticosteroids to reduce short-term mortality, as tested by the clinical utility of the MDF score.
Full handout
High yield triage
Etiology / Epidemiology
Driven by chronic heavy alcohol consumption; risk correlates with total lifetime dose and female sex.
Clinical Manifestations
Presents with spider angiomata, jaundice, and caput medusae; suspect alcohol-associated hepatitis in acute decompensation.
Diagnosis
AST:ALT ratio > 2:1 is highly suggestive; liver biopsy remains the reference standard for staging.
Treatment
Primary management is alcohol cessation; use prednisolone for severe cases (Maddrey score ≥ 32).
Prognosis
High mortality in severe hepatitis; Maddrey Discriminant Function score ≥ 32 predicts poor outcomes.
Full handout
Epidemiology & Etiology
Alcohol-associated liver disease (formerly alcoholic liver disease) progresses from steatosis to hepatitis and eventually cirrhosis. Under the 2023 steatotic liver disease nomenclature, patients with cardiometabolic risk factors and moderate intake (about 140–350 g/week in women, 210–420 g/week in men) are classified as MetALD. Women are at higher risk due to lower gastric alcohol dehydrogenase activity. Daily intake exceeding 80g/day for over a decade is the classic threshold for significant injury.
Pertinent Anatomy
The liver is the primary site of ethanol metabolism via the cytochrome P450 2E1 pathway. Chronic inflammation leads to perivenular fibrosis and eventual architectural distortion of the hepatic lobules. Portal hypertension results from increased resistance to blood flow through the fibrotic liver parenchyma.
Pathophysiology
Ethanol metabolism increases the NADH/NAD+ ratio, promoting fatty acid synthesis and inhibiting fatty acid oxidation. This leads to steatosis, which can progress to inflammation and necrosis. Acetaldehyde, a toxic byproduct, induces oxidative stress and triggers an immune-mediated inflammatory response.
Clinical Manifestations
Patients often present with hepatomegaly, jaundice, and ascites. Look for palmar erythema and Dupuytren's contractures as signs of chronic disease. Acute alcohol-associated hepatitis manifests as sudden fever, tender hepatomegaly, and leukocytosis; hepatic encephalopathy is a critical red flag.
Diagnosis
The AST:ALT ratio > 2:1 is a classic board finding, rarely exceeding 500 IU/L. Liver biopsy is the reference standard to distinguish steatosis from alcohol-associated hepatitis or cirrhosis. Calculate the Maddrey Discriminant Function (DF) using prothrombin time and bilirubin to guide steroid therapy.
Treatment
Strict alcohol cessation is the most important intervention for improving long-term survival. For severe alcohol-associated hepatitis (MDF ≥32 per AASLD 2019, or MELD >20 per ACG 2024), prednisolone is the first-line pharmacotherapy. Pentoxifylline is no longer recommended (AASLD 2019; ACG 2024), including when steroids are contraindicated. Avoid acetaminophen due to synergistic hepatotoxicity.
Prognosis
Patients with cirrhosis are at high risk for hepatocellular carcinoma and warrant ultrasound surveillance every 6 months. The MELD score is used to prioritize patients for liver transplantation, which typically requires a documented commitment to abstinence.
Differential Diagnosis
MASLD (formerly NAFLD): AST:ALT ratio typically < 1
Viral Hepatitis: ALT > AST usually
Wilson Disease: Low ceruloplasmin levels
Hemochromatosis: Elevated ferritin and transferrin saturation
Drug-induced liver injury: History of acetaminophen or toxin exposure