In a 35-year-old woman with low blood urea nitrogen (BUN) of 3 mg/dL, BUN/creatinine ratio of 5, total bilirubin 1.8 mg/dL, alkaline phosphatase 172 U/L, aspartate aminotransferase (AST) 242 U/L, and alanine aminotransferase (ALT) 134 U/L, what is the most likely diagnosis and the appropriate first‑line treatment?

Diagnosis and Treatment

This 35-year-old woman most likely has acute hepatocellular injury with a cholestatic component, and the immediate priority is to determine whether this represents fulminant Wilson disease, acute viral hepatitis, drug-induced liver injury, or autoimmune hepatitis—each requiring distinct urgent management.

Critical Diagnostic Considerations

Pattern Recognition

The laboratory pattern reveals:

• Severe hepatocellular injury: AST 242 U/L and ALT 134 U/L represent moderate elevation (5-10× upper limit of normal for women, whose normal ALT is 19-25 IU/L) 1
• AST/ALT ratio of 1.8: This ratio >1 is atypical for most causes of acute hepatitis but highly characteristic of alcoholic liver disease or Wilson disease 1, 2
• Cholestatic component: Alkaline phosphatase 172 U/L with bilirubin 1.8 mg/dL suggests concurrent bile flow impairment 2
• Profoundly low BUN (3 mg/dL): This is pathognomonic for severe liver synthetic dysfunction and indicates the liver cannot produce urea from ammonia—a red flag for acute liver failure 3
• BUN/creatinine ratio of 5: Abnormally low, further confirming impaired hepatic urea synthesis 3

Most Urgent Differential: Fulminant Wilson Disease

Wilson disease presenting as acute liver failure must be ruled out immediately because it is uniformly fatal without emergency liver transplantation 4. In a 35-year-old woman with this pattern:

• Calculate the alkaline phosphatase-to-bilirubin ratio: 172 ÷ 1.8 = 95.6. A ratio <4 has 94% sensitivity and 96% specificity for fulminant Wilson disease 4
• The AST/ALT ratio >2.2 has 94% sensitivity and 86% specificity for Wilson disease 4
• Order immediately: Serum ceruloplasmin (by oxidase method), serum copper, 24-hour urine copper, and slit-lamp examination for Kayser-Fleischer rings 4
• Critical pitfall: Ceruloplasmin measured by nephelometry has only 56% sensitivity; the oxidase method is superior 4

Alternative Diagnoses Requiring Immediate Evaluation

Autoimmune Hepatitis

• Women aged 20-40 are the highest-risk group 2
• Order: ANA, anti-smooth muscle antibody (ASMA), quantitative IgG, and gamma globulin 2
• If positive, initiate corticosteroids immediately while awaiting confirmatory testing 2

Acute Viral Hepatitis

• Order: Hepatitis A IgM, HBsAg, HBc IgM, HCV antibody with reflex PCR 1, 2
• Hepatitis E should be considered in women of childbearing age 2

Drug-Induced Liver Injury

• Review all medications, supplements, and herbal products against the LiverTox® database 1
• Medication-induced injury causes 8-11% of elevated transaminases 1
• Discontinue any potentially hepatotoxic agent immediately if ALT >5× ULN 1

Immediate Diagnostic Work-Up (Within 24 Hours)

Essential Laboratory Tests

1. Complete liver panel:

   • Albumin, prothrombin time/INR (to assess synthetic function) 1, 2
   • Total and direct bilirubin fractionation 2
   • Complete blood count (check for thrombocytopenia, anemia) 1

2. Wilson disease screening:

   • Serum ceruloplasmin (oxidase method) 4
   • Serum copper (expect >200 µg/dL in Wilson disease) 4
   • 24-hour urine copper 4

3. Viral hepatitis serologies:

   • HAV IgM, HBsAg, HBc IgM, HCV antibody 1, 2

4. Autoimmune markers:

   • ANA, ASMA, quantitative IgG 1, 2

5. Metabolic parameters:

   • Fasting glucose or HbA1c, fasting lipid panel 1
   • Iron studies (ferritin, transferrin saturation) 1

Imaging

• Abdominal ultrasound immediately: To assess for biliary obstruction, hepatic steatosis, portal hypertension, and structural abnormalities 1, 5
• Ultrasound has 84.8% sensitivity and 93.6% specificity for detecting moderate-to-severe steatosis 1

Treatment Algorithm

If Wilson Disease is Confirmed or Highly Suspected

Urgent hepatology referral for liver transplant evaluation 4. Wilson disease presenting as acute liver failure is 100% fatal without transplantation 4.

If Autoimmune Hepatitis is Diagnosed

• Initiate prednisone 40-60 mg daily (or equivalent corticosteroid) 2
• Add azathioprine 50 mg daily after 2 weeks if tolerated 2
• Monitor liver enzymes weekly initially 2

If Drug-Induced Liver Injury is Suspected

• Discontinue the offending medication immediately 1
• Monitor ALT every 3-7 days until declining 1
• Expect normalization within 2-8 weeks after drug discontinuation 1

If Viral Hepatitis is Confirmed

• Hepatitis A or E: Supportive care, monitor for fulminant hepatic failure 2
• Hepatitis B: Consider antiviral therapy if evidence of acute liver failure 2
• Hepatitis C: Refer to hepatology for treatment planning 2

If Non-Alcoholic Fatty Liver Disease (NAFLD) is Diagnosed

• Lifestyle modifications: Target 7-10% weight loss through caloric restriction 1
• Low-carbohydrate, low-fructose diet 1
• 150-300 minutes/week of moderate-intensity aerobic exercise 1
• Manage metabolic syndrome components aggressively 1

Monitoring Strategy

Immediate (First 48-72 Hours)

• Repeat liver enzymes, bilirubin, albumin, and INR to establish trend 1
• If ALT increases to >5× ULN or bilirubin >2× ULN, urgent hepatology referral 1
• If INR >1.5 or albumin <3.0 g/dL, consider acute liver failure and transfer to transplant center 1

Short-Term (First 2 Weeks)

• Repeat liver panel every 3-7 days until enzymes are declining 1
• Monitor for signs of hepatic decompensation: ascites, encephalopathy, coagulopathy 1

Long-Term (After Stabilization)

• If enzymes remain elevated >6 months, hepatology referral for possible liver biopsy 1, 2
• Calculate FIB-4 score to assess fibrosis risk 1

Critical Pitfalls to Avoid

1. Do not assume NAFLD with this degree of transaminase elevation and low BUN—this pattern suggests acute severe injury 1

2. Do not delay Wilson disease testing in any patient <40 years with unexplained hepatitis and AST/ALT ratio >1 4

3. Do not overlook the profoundly low BUN—this indicates severe hepatic synthetic dysfunction and warrants immediate specialist consultation 3

4. Do not wait for symptoms to worsen before referring—acute liver failure can progress rapidly 1

5. Do not attribute elevated transaminases to "fatty liver" without excluding Wilson disease, autoimmune hepatitis, and viral hepatitis 1, 4