What is the likely diagnosis in a patient with moderately elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and normal bilirubin?

Differential Diagnosis: Moderately Elevated Transaminases with Normal Bilirubin

The most likely diagnosis is acute choledocholithiasis (bile duct stone) causing transient biliary obstruction, which can present with marked transaminase elevation mimicking acute hepatitis while bilirubin remains normal in early or partial obstruction. 1

Understanding the Enzyme Pattern

Your ALT of 206 IU/L and AST of 238 IU/L represent moderate elevations (approximately 5–7× the upper limit of normal for most laboratories), creating a predominantly hepatocellular injury pattern 2. However, the normal bilirubin is the critical clue that distinguishes this from typical acute hepatitis 1.

Why Choledocholithiasis Should Be Considered First

• Bile duct stones frequently cause marked transaminase elevations (often >400 IU/L) that can exceed alkaline phosphatase, mimicking acute viral hepatitis, yet bilirubin may remain normal in early or partial obstruction 1
• In documented cases of choledocholithiasis without hepatocellular disease, patients presented with severe transaminase elevations but rapid normalization after biliary decompression 1
• The combination of elevated transaminases with normal bilirubin strongly suggests biliary disease rather than primary hepatic pathology 1

Primary Differential Diagnoses

1. Acute Choledocholithiasis (Most Likely)

• Presents with sudden-onset right upper quadrant pain and transaminase spikes 1
• Bilirubin elevation may lag behind transaminase rise or remain normal with partial obstruction 1
• Requires urgent abdominal ultrasound to identify bile duct stones or dilation 2
• If ultrasound shows common bile duct stones, proceed directly to ERCP within 24–72 hours 3

2. Acute Viral Hepatitis (Hepatitis A, B, or E)

• Typically shows ALT >400 IU/L in acute infection 4
• Viral hepatitis serologies (HBsAg, HBc IgM, HAV IgM, HCV antibody) should be obtained immediately 2
• Bilirubin usually rises within days of transaminase elevation 4

3. Ischemic Hepatitis ("Shock Liver")

• Occurs after hypotensive episodes, cardiac arrest, or severe hypoxia 4
• Characterized by massive transaminase elevations (often >1000 IU/L) with rapid decline within 48–72 hours 4
• Associated with elevated lactate dehydrogenase and cardiac biomarkers 4

4. Drug-Induced Liver Injury (DILI)

• Accounts for 14% of cases with transaminases >400 IU/L 4
• Review all prescription medications, over-the-counter drugs, and herbal supplements against the LiverTox® database 2
• Medication-induced injury causes 8–11% of mildly elevated transaminases but can present with higher elevations 2

5. Acute Exacerbation of Chronic Hepatitis B or C

• Represents 22% of marked transaminase elevations in non-transplant patients 4
• Chronic viral hepatitis commonly presents with fluctuating transaminase elevations 2
• Requires viral load testing (HBV DNA, HCV RNA) if serologies are positive 2

6. Non-Alcoholic Fatty Liver Disease (NAFLD) – Less Likely

• NAFLD typically shows AST:ALT ratio <1 with mild-to-moderate elevations (<5× ULN) 2
• Elevations ≥5× ULN are rare in NAFLD and should not be attributed to this condition alone 2
• Assess for metabolic syndrome components (obesity, diabetes, hypertension, dyslipidemia) 2

7. Alcoholic Hepatitis – Less Likely

• Characterized by AST:ALT ratio >2 in 70% of cases, with AST typically 2–6× ULN 2
• Your AST:ALT ratio of 1.16 makes alcoholic hepatitis unlikely 2
• Obtain detailed alcohol history (>40 g/day for women, >50–60 g/day for men for ≥6 months) 2

Immediate Diagnostic Algorithm

Step 1: Urgent Laboratory Testing (Within 24 Hours)

• Complete liver panel: AST, ALT, alkaline phosphatase, GGT, total and direct bilirubin, albumin, PT/INR 2
• Viral hepatitis serologies: HBsAg, HBc IgM, HAV IgM, HCV antibody 2
• Complete blood count to assess for hemolysis or infection 2
• Creatine kinase (CK) to exclude rhabdomyolysis as a source of AST elevation 2

Step 2: Urgent Imaging (Within 24–48 Hours)

• Abdominal ultrasound is the first-line test with 84.8% sensitivity and 93.6% specificity for detecting bile duct stones and dilation 2
• If ultrasound shows common bile duct stones, proceed directly to ERCP without further imaging 3
• If ultrasound is negative but clinical suspicion remains high, obtain MRI with MRCP to detect intrahepatic biliary abnormalities 2

Step 3: Repeat Liver Enzymes in 2–5 Days

• Rapidly declining transaminases suggest ischemic hepatitis or resolving biliary obstruction 4
• Persistently elevated or rising transaminases warrant hepatology referral 2

Critical Pitfalls to Avoid

• Do not assume that elevated transaminases exclude biliary obstruction—in acute choledocholithiasis, ALT can surpass alkaline phosphatase, mimicking acute hepatitis 1
• Do not attribute transaminase elevations ≥5× ULN to NAFLD without excluding other causes—such elevations are rare in NAFLD alone 2
• Do not overlook medication-induced liver injury—review all drugs, including over-the-counter and herbal supplements 2
• Do not delay imaging while awaiting laboratory results—ultrasound should be performed urgently to identify treatable biliary obstruction 2
• Do not ignore the AST:ALT ratio—a ratio >2 suggests alcoholic liver disease, while <1 suggests NAFLD or viral hepatitis 2

When to Refer to Hepatology

• ALT >5× ULN (>235 IU/L for males, >125 IU/L for females) 2
• Bilirubin >2× ULN 2
• Evidence of synthetic dysfunction (low albumin, elevated INR, thrombocytopenia) 2
• Transaminases remain elevated for ≥6 months without identified cause 2
• FIB-4 score >2.67 indicating high risk for advanced fibrosis 2

Summary of Most Likely Diagnosis

Given the moderate transaminase elevation with normal bilirubin, acute choledocholithiasis is the most probable diagnosis, particularly if accompanied by right upper quadrant pain 1. This pattern reflects transient biliary obstruction causing hepatocyte injury before jaundice develops 1. Urgent abdominal ultrasound is the single most important next step to identify bile duct stones and guide immediate management 2, 1.