What are the potential causes of transaminitis in a jaundiced adult patient with possible underlying conditions such as viral hepatitis, alcoholic liver disease, or autoimmune hepatitis?

Causes of Transaminitis in Jaundiced Adults

In a jaundiced adult with transaminitis, the most common etiologies are alcoholic hepatitis, sepsis/shock, decompensation of pre-existing cirrhosis, and drug-induced liver injury, with the specific pattern of liver enzyme elevation helping distinguish between these causes. 1

Algorithmic Approach Based on Transaminase Pattern

AST/ALT Ratio >1.5 with Modest Elevation (AST/ALT typically <400 IU/mL)

This pattern strongly suggests alcoholic hepatitis, which accounts for 16% of jaundice cases and represents one of the four most common causes of jaundice in the United States. 1

• Alcoholic hepatitis requires heavy alcohol consumption (>50-60 g/day for men, >40 g/day for women) for at least 6 months with <60 days of abstinence before jaundice onset. 1, 2
• The AST/ALT ratio of >1.5 is seen in >98% of histologically proven alcoholic hepatitis cases. 1
• Female sex, elevated BMI, and PNPLA3 genetic polymorphisms increase susceptibility. 2
• Bilirubin is typically >3 mg/dL with tender hepatomegaly and potential decompensation (ascites, encephalopathy). 1

Marked Transaminase Elevation (AST/ALT >400 IU/mL)

This pattern indicates acute viral hepatitis, drug-induced liver injury, or ischemic hepatitis, distinguishing these from alcoholic hepatitis which rarely exceeds 400 IU/mL. 1

• Drug-induced liver injury (DILI) constitutes one of the four most common causes of jaundice and includes toxic reactions to medications or herbal supplements. 1, 2
• Viral hepatitis accounts for only 0.2% of severe jaundice cases but causes marked transaminase elevation. 1
• Ischemic hepatitis/sepsis represents 22-27% of severe jaundice cases and creates dual mechanisms through both hemolysis and hepatic dysfunction. 1, 2

Transaminitis with Pre-existing Chronic Liver Disease

Decompensation of cirrhosis is the second most common cause of new-onset jaundice (20.5% of cases) and the primary mechanism in established chronic liver disease patients. 2

• Precipitating factors include sepsis, alcoholic hepatitis superimposed on cirrhosis (acute-on-chronic liver failure), and hemolysis. 1, 2
• Coombs-negative hemolytic anemia occurs in 10-25% of chronic liver disease patients presenting with jaundice. 2
• The majority of patients with severe alcoholic hepatitis have underlying cirrhosis. 1

Critical Distinction: Conjugated vs Unconjugated Hyperbilirubinemia

Unconjugated (Hepatocellular) Pattern

• Hepatitis/sepsis, alcoholic liver disease, and hemolysis cause predominantly unconjugated hyperbilirubinemia. 1
• Gilbert syndrome accounts for 5.6% of jaundice cases with constitutional predisposition. 2

Conjugated (Obstructive) Pattern

• Common bile duct obstruction from stones (13-14% of cases) or tumor (6.2% of U.S. cases) causes conjugated hyperbilirubinemia. 1, 2
• Choledocholithiasis sensitivity on ultrasound ranges from 22.5-75%, lower than for gallbladder stones due to overlying bowel gas. 1
• Malignancy represents the most common etiology of severe jaundice in European populations despite lower prevalence in U.S. studies. 2

Common Pitfalls to Avoid

Do not assume alcoholic hepatitis based solely on alcohol history without checking the AST/ALT ratio and excluding other causes. 1

• Viral hepatitis, severe autoimmune liver disease, and Wilson disease must be tested for even with heavy alcohol use. 1
• 10-20% of patients with clinical diagnosis of alcoholic hepatitis have other liver diseases found only by biopsy. 1

Do not overlook sepsis as a cause, which is the most common etiology of new-onset jaundice (22%) and can mimic primary hepatic disease. 1

Transaminase levels <400 IU/mL do not exclude serious pathology but help narrow the differential toward alcoholic hepatitis, cirrhosis decompensation, or biliary obstruction rather than acute viral hepatitis or DILI. 1

Initial Diagnostic Workup

• Abdominal ultrasound is the initial imaging of choice with 65-95% sensitivity for cirrhosis and 32-100% sensitivity for biliary obstruction. 1, 2
• Fractionated bilirubin, complete blood count, hepatic profile, and coagulation studies distinguish between hepatocellular and obstructive patterns. 1, 3
• Liver biopsy may be required when etiology remains unclear despite laboratory testing and imaging, particularly to confirm alcoholic hepatitis in atypical presentations. 1, 3