What should I do about elevated liver enzymes (hypertransaminasemia), with ALT at 328 and AST at 135?

Management of Significantly Elevated Liver Enzymes (ALT 328, AST 135)

Your ALT of 328 U/L represents a severe elevation (>10× upper limit of normal for women, >5× for men) that requires immediate comprehensive evaluation within 2-3 days, as this degree of hepatocellular injury warrants urgent assessment for potentially serious causes including viral hepatitis, autoimmune hepatitis, drug-induced liver injury, or ischemic hepatitis. 1, 2

Severity Classification and Urgency

Your enzyme pattern indicates:

• ALT 328 U/L: This is severe elevation (>10× ULN using female reference range of 19-25 IU/L, or >5× ULN using male reference of 29-33 IU/L) 1
• AST 135 U/L: Moderate elevation, with AST:ALT ratio <1, which is characteristic of non-alcoholic fatty liver disease, viral hepatitis, or medication-induced injury rather than alcoholic liver disease 1, 2
• This pattern represents Grade 2-3 hepatocellular injury requiring prompt action 1

Critical point: ALT elevations ≥5× ULN are rare in benign conditions like NAFLD alone and should not be attributed to fatty liver without excluding more serious causes 1

Immediate Actions Required (Within 2-3 Days)

Laboratory Testing

Repeat comprehensive liver panel immediately including: 1, 2

• Complete liver panel: AST, ALT, alkaline phosphatase, GGT, total and direct bilirubin, albumin, PT/INR
• Viral hepatitis serologies: HBsAg, anti-HBc (IgM and total), anti-HCV antibody 1, 2
• Autoimmune markers: ANA, anti-smooth muscle antibody (ASMA), immunoglobulin levels (particularly IgG) 1
• Creatine kinase (CK): To exclude muscle injury as source of AST elevation 1, 2
• Thyroid function tests: TSH, free T4 1, 2
• Iron studies: Serum ferritin and transferrin saturation (>45% is significant for hemochromatosis) 3

Medication and Exposure Review

Immediately review and document: 1, 2

• All prescription medications (including recent additions or dose changes)
• Over-the-counter medications (particularly acetaminophen, NSAIDs)
• Herbal supplements and vitamins
• Alcohol consumption (quantify drinks per week)
• Recent illnesses, hypotensive episodes, or cardiac events (ischemic hepatitis)
• Exposure to hepatotoxins

Consider discontinuing any potentially hepatotoxic medications if safe to do so, as drug-induced liver injury is a common cause of this pattern 1

Imaging Evaluation

Order abdominal ultrasound with Doppler before or concurrent with specialist referral: 1, 2

• Assesses for hepatic steatosis (sensitivity 84.8%, specificity 93.6% for moderate-severe steatosis)
• Identifies biliary obstruction or dilation
• Detects focal liver lesions or masses
• Evaluates for vascular abnormalities (Budd-Chiari, portal vein thrombosis)
• Assesses liver texture and spleen size

Specialist Referral Criteria

Hepatology referral is warranted given your ALT >5× ULN: 1, 2

• Refer urgently (within 1-2 weeks) for evaluation
• Immediate referral (within 2-3 days) if:
  • Bilirubin rises to >2× ULN
  • INR becomes elevated (>1.3)
  • Development of hepatic symptoms (jaundice, confusion, ascites)
  • ALT continues to rise on repeat testing

Risk Stratification for Fibrosis

Calculate FIB-4 score using: age, ALT, AST, and platelet count: 1, 2

• FIB-4 >2.67: High risk for advanced fibrosis, strengthens need for hepatology referral
• This helps determine urgency and need for additional evaluation including possible liver biopsy

Monitoring Schedule

Initial phase (until declining trend established): 1, 2

• Repeat liver panel every 2-3 days initially
• Once declining, reduce to 2-3 times weekly
• When stable/improving, reduce to weekly until normalization

Expected timeline: If drug-induced, ALT should decline within 2-8 weeks after discontinuation of offending agent 1

Most Likely Differential Diagnoses at This Level

Given the severity of elevation, prioritize evaluation for: 1

1. Viral hepatitis (acute hepatitis A, B, C, or E)
2. Drug-induced liver injury (prescription, OTC, or herbal)
3. Autoimmune hepatitis (especially if female, elevated IgG)
4. Ischemic hepatitis (if recent hypotension, cardiac event, or shock)
5. Acute biliary obstruction (gallstones, though typically more cholestatic pattern)

Less likely at this severity: NAFLD alone rarely causes ALT >5× ULN 1

Critical Pitfalls to Avoid

• Don't assume this is "just fatty liver": ALT ≥5× ULN requires investigation for serious causes 1
• Don't delay repeat testing: This level warrants 2-3 day follow-up regardless of symptoms 1, 2
• Don't overlook non-hepatic causes: Check CK to exclude rhabdomyolysis or muscle injury, especially if recent intense exercise 1, 2
• Don't miss medication causes: Review ALL medications including supplements; even "natural" products can cause severe hepatotoxicity 1, 2
• Don't ignore synthetic function: Normal albumin and bilirubin now is reassuring, but monitor closely as deterioration indicates more severe injury 1

Lifestyle Modifications (While Awaiting Workup)

Immediate measures: 1, 2

• Complete alcohol abstinence (even moderate consumption can worsen liver injury)
• Avoid hepatotoxic substances (acetaminophen, NSAIDs unless essential)
• Maintain adequate hydration
• Avoid fasting or extreme dietary changes until diagnosis established

Prognosis and Reassurance

If synthetic function remains normal (albumin, bilirubin, INR): 1

• This indicates preserved liver function despite hepatocellular injury
• Most causes of acute hepatocellular injury resolve with appropriate management
• Early identification and intervention significantly improve outcomes

However, close monitoring is essential as progression to acute liver failure, though uncommon, can occur rapidly with certain etiologies 1, 2