Gastroenterology · Hepatology
The facts most likely to be tested
Alcoholic 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 the pathognomonic histologic finding seen on liver biopsy in patients with alcoholic liver disease.
The Maddrey Discriminant Function (MDF) score is used to determine the severity of alcoholic hepatitis and the necessity for corticosteroid therapy.
Pentoxifylline is an alternative treatment for severe alcoholic hepatitis in patients who have contraindications to corticosteroids.
Patients with alcoholic liver disease frequently present with macrocytosis (elevated MCV) due to the direct toxic effect of ethanol on the bone marrow.
Alcoholic 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 in all stages of alcoholic liver disease.
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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 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.
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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 alcoholic hepatitis in acute decompensation.
Diagnosis
AST:ALT ratio > 2:1 is highly suggestive; liver biopsy remains the gold standard for definitive 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.
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Epidemiology & Etiology
Alcoholic liver disease progresses from steatosis to hepatitis and eventually cirrhosis. 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 alcoholic 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 gold standard to distinguish steatosis from alcoholic hepatitis or cirrhosis. Calculate the Maddrey Discriminant Function (DF) using prothrombin time and bilirubin to guide steroid therapy.
Treatment
Strict alcohol cessation is the only intervention that improves long-term survival. For severe alcoholic hepatitis (DF ≥ 32), prednisolone is the first-line pharmacotherapy. Pentoxifylline is an alternative if steroids are contraindicated, though efficacy is debated. Avoid acetaminophen due to synergistic hepatotoxicity.
Prognosis
Patients with cirrhosis are at high risk for hepatocellular carcinoma and require biannual ultrasound screening. The MELD score is used to prioritize patients for liver transplantation, which requires a documented period of abstinence.
Differential Diagnosis
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