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Am Fam Physician. 2022;105(4):412-420

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial relationships.

Alcoholic hepatitis is a clinical syndrome characterized by acute-onset jaundice and liver enzyme abnormalities in the setting of long-term heavy alcohol use. High rates of concomitant infections, systemic inflammation, and multiorgan failure lead to significant morbidity and mortality. Diagnosis of alcoholic hepatitis is primarily clinical, based on a consensus definition from the National Institute on Alcohol Abuse and Alcoholism. Initial workup should include chest radiography and cultures of peritoneal fluid, blood, and urine. Close monitoring for inflammation and organ failure is crucial throughout hospitalization. Laboratory-based prognostic scores, including Maddrey Discriminant Function and the Model for End-Stage Liver Disease, help determine disease severity and treatment options. Treatment for moderate disease primarily consists of supportive care, including alcohol cessation and nutritional support. Corticosteroids are recommended for severe alcoholic hepatitis. Responsiveness to corticosteroid therapy should be evaluated using the Lille score on day 7 of treatment. Hospital physicians should involve a multidisciplinary team, including substance abuse specialists, gastroenterologists or hepatologists, nephrologists, dietitians, and intensivists, as appropriate. Long-term follow-up should focus on abstinence from alcohol, management of underlying cirrhosis, and evaluation for liver transplantation if indicated. Pharmacologic treatment of alcohol use disorder can aid patients in maintaining abstinence from alcohol. The presence of underlying cirrhosis and continued alcohol use negatively impact long-term prognosis.

Alcohol-associated liver disease encompasses a range of pathologies from hepatic steatosis to cirrhosis. Decompensated liver disease can manifest as ascites, variceal hemorrhage, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome, hepatopulmonary syndrome, or hepatocellular carcinoma. Alcoholic hepatitis is a clinical syndrome associated with acute-onset jaundice and liver failure.1 High rates of concomitant infections, systemic inflammation, and multiorgan failure lead to significant morbidity and mortality.

Epidemiology and Risk Factors

The incidence of alcoholic hepatitis is difficult to estimate because of inconsistency in diagnosis of the disease and overlap with concurrent, more easily diagnosed liver diseases, such as hepatitis C.1,2 However, hospital admissions for alcoholic hepatitis are on the rise in the United States, accounting for 0.83% of all admissions in 2010.1 Risk factors for the development of the disease include prolonged and heavy alcohol use, younger age, female sex, genetic susceptibility, higher body mass index, and comorbid liver disease.1,35 Overall and in-hospital mortality are high for severe alcoholic hepatitis, with a 28-day mortality rate of 16% to 30% and a one-year mortality rate of 56%.6 The presence of underlying cirrhosis and continued alcohol use negatively impact long-term prognosis.4,79

Diagnosis

Because of historical variability in the diagnosis of alcoholic hepatitis, the National Institute on Alcohol Abuse and Alcoholism developed a consensus statement for diagnosing the disease (Table 1).1,7,10 The diagnosis is primarily clinical and must include acute-onset jaundice, specific laboratory abnormalities, and characteristic history of alcohol use (i.e., long-term consumption of roughly three standard drinks daily for women and four standard drinks daily for men). Liver biopsy is necessary only if the diagnosis is unclear and accurate diagnosis would impact management.7,10

Diagnostic criteria
 Jaundice onset within previous 8 weeks
 Long-term consumption of alcohol: > 40 g (roughly 3 standard drinks) daily for women or > 60 g (roughly 4 standard drinks) daily for men for ≥ 6 months, with < 60 days of abstinence before onset of jaundice
 AST > 50 U per L (0.83 μkat per L), AST/ALT ratio > 1.5, and both AST and ALT < 400 U per L (6.68 μkat per L)
 Total bilirubin > 3 mg per dL (51.31 μmol per L)
 Absence of confounding factors
Confounding factors
 Possible ischemic hepatitis (suggested by severe upper gastrointestinal tract bleed, hypotension, cocaine use within seven days of symptom onset)
 Possible metabolic liver disease (Wilson disease, alpha1-antitrypsin deficiency)
 Possible drug-induced liver disease (use of offending drug within 30 days of jaundice onset)
 Uncertain alcohol use assessment (patient denies excessive alcohol use)
 Atypical laboratory findings (AST < 50 U per L or > 400 U per L, AST/ALT ratio < 1.5, antinuclear antibodies > 1: 160, or anti–smooth muscle antibodies > 1: 80)
If diagnostic confirmation would change management in the presence of confounding factors, perform liver biopsy

CLINICAL PRESENTATION AND LABORATORY FINDINGS

Acute onset of jaundice is the only clinical sign or symptom required for the diagnosis of alcoholic hepatitis.7,10 However, other nonspecific signs and symptoms (Table 21,11,12 and Figure 1) can support the diagnosis of alcoholic hepatitis and suggest underlying chronic alcohol-associated liver disease. Because these signs and symptoms can be subtle, a high index of suspicion is required. Laboratory findings that are diagnostic for alcoholic hepatitis or characteristic of alcohol-associated liver disease are outlined in Table 21,11,12; deviation from the specified diagnostic pattern should prompt consideration of alternative diagnoses.

Symptoms
Abdominal pain (right upper quadrant, epigastric)
Anorexia
Confusion (encephalopathy)
Fatigue
Fever
Malaise
Nausea and vomiting
Peripheral neuropathy
Sleep-wake inversion
Weight gain (ascites)
Weight loss (loss of muscle mass, malnutrition)
Laboratory tests
Diagnostic findings
 AST > 50 U per L (0.83 μkat per L)
 AST/ALT ratio > 1.5
 AST and ALT < 400 U per L (6.68 μkat per L)
 Total bilirubin > 3 mg per dL (51.31 μmol per L)
Other characteristic findings
 Decreased serum albumin and prealbumin
 Elevated gamma-glutamyltransferase
 Elevated international normalized ratio
 Elevated white blood cell count with neutrophil predominance
 Macrocytosis
 Thiamine deficiency
 Thrombocytopenia
 Vitamin B12 and/or folate deficiency

CHARACTERISTIC ALCOHOL USE HISTORY

Presence of the characteristic alcohol use history is an important component of the clinical diagnosis, and patient reluctance to disclose alcohol use is a significant issue.13 Validated screening tools (Table 310,1417) and collateral history from family members can aid in identifying high-risk alcohol use.1 The Alcohol Use Disorders Identification Test-Concise screening questionnaire is a more targeted screening tool for identifying alcohol misuse than the CAGE (cut down, annoyed, guilty, eye-opener) questionnaire.14

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