What is the management and treatment approach for transaminitis (elevated liver enzymes)?

Management and Treatment of Transaminitis (Elevated Liver Enzymes)

The management of transaminitis requires a systematic approach based on severity, etiology, and patient factors, with treatment directed at the underlying cause while monitoring liver function until normalization.

Evaluation and Grading

• Transaminitis is graded based on elevation of AST/ALT levels:

  • Grade 1: AST/ALT > ULN to 3.0× ULN
  • Grade 2: AST/ALT > 3.0 to 5.0× ULN
  • Grade 3: AST/ALT > 5.0 to 20× ULN
  • Grade 4: AST/ALT > 20× ULN 1

• Initial workup should include:

  • Review of medications and supplements with hepatotoxic potential
  • Evaluation for viral hepatitis, alcohol history, iron studies
  • Assessment for thromboembolic events or liver metastases
  • Imaging (ultrasound and cross-sectional imaging) for grades ≥2 1

Management Based on Severity

Grade 1 (AST/ALT > ULN to 3.0× ULN)

• Close monitoring without specific treatment
• Consider monitoring labs 1-2 times weekly
• Identify and address potential causes 1

Grade 2 (AST/ALT > 3.0 to 5.0× ULN)

• Discontinue potential hepatotoxic medications if medically feasible
• Increase monitoring frequency to every 3 days
• Consider prednisone 0.5-1 mg/kg/day if no improvement after 3-5 days
• Consider hepatology consultation 1

Grade 3 (AST/ALT > 5.0 to 20× ULN)

• Urgent hepatology consultation
• Discontinue hepatotoxic medications
• Start methylprednisolone 1-2 mg/kg/day or equivalent
• Consider liver biopsy if steroid-refractory or diagnostic uncertainty
• Consider adding mycophenolate mofetil or azathioprine if inadequate response to steroids 1

Grade 4 (AST/ALT > 20× ULN)

• Immediate hospitalization, preferably at a liver center
• Permanently discontinue causative agents
• Administer methylprednisolone 2 mg/kg/day with planned 4-6 week taper
• Add second-line immunosuppression (mycophenolate, azathioprine, tacrolimus) if transaminases don't decrease by 50% within 3 days 1

Management Based on Etiology

Drug-Induced Liver Injury

• Identify and discontinue the offending agent

• For immune checkpoint inhibitor-related hepatitis:

  • Grade 2: Hold ICI and monitor; resume when recovered to grade 1
  • Grade 3-4: Permanently discontinue ICI and start steroids 1

• For tuberculosis medication-induced hepatitis:

  • If AST/ALT rises to 5× ULN or bilirubin rises, stop rifampicin, isoniazid, and pyrazinamide
  • Once liver function normalizes, reintroduce drugs sequentially with careful monitoring 1

Autoimmune Hepatitis

• Initiate immunosuppressive therapy with prednisone ± azathioprine
• Continue treatment for at least 3 years and for at least 2 years after complete normalization of transaminases and IgG
• Monitor for relapse after treatment withdrawal, which occurs in 50-90% of patients 1

Viral Hepatitis

• Treatment depends on specific viral etiology
• For chronic hepatitis C, direct-acting antivirals are the standard of care 2

Special Considerations

Chronic Liver Disease

• Regular monitoring of liver function (weekly for two weeks, then biweekly for two months) is required for patients with known chronic liver disease 1

Alcohol-Related Liver Disease

• Complete alcohol cessation is essential
• Nutritional support and management of complications
• Use caution with medications like paracetamol in alcoholic patients, as even therapeutic doses can cause severe hepatitis 3

Pregnancy and Postpartum

• Be vigilant for medication-induced liver injury during pregnancy and postpartum
• Labetalol can rarely cause chronic DILI in the postpartum period 4

Monitoring and Follow-up

• For mild transaminitis (grade 1), monitor liver function tests every 1-2 weeks

• For moderate to severe transaminitis (grades 2-4), more frequent monitoring is required

• Continue monitoring until normalization of liver enzymes 1

• For drug rechallenge after DILI:

  • Wait for complete normalization of liver enzymes
  • Reintroduce at lower doses with careful monitoring
  • For sequential reintroduction of TB medications: start with isoniazid at 50 mg/day, gradually increase to 300 mg/day; then add rifampicin at 75 mg/day, gradually increase; finally add pyrazinamide 1

Pitfalls and Caveats

• Modest elevations of transaminases are common and may not indicate significant liver disease; 40% of patients with mild transaminitis have liver steatosis 2
• Infliximab is contraindicated for immune-related hepatitis 1
• Chronic hepatitis of unknown etiology accounts for approximately 24% of cases of persistent mild transaminitis 2
• Patients on tyrosine kinase inhibitors require regular monitoring for hepatotoxicity, with incidence varying widely between agents 1