What is the management and treatment approach for patients with deranged liver function test (LFT) parameters?

Management of Deranged Liver Function Tests

Patients with abnormal liver function tests should undergo a systematic investigation to determine the underlying cause, with management tailored to the specific etiology, pattern of liver injury, and severity of derangement. 1

Initial Assessment of Abnormal LFTs

Patterns of Liver Injury

• Hepatocellular pattern: Predominant elevation of ALT/AST
• Cholestatic pattern: Predominant elevation of ALP/GGT
• Mixed pattern: Elevation of both transaminases and cholestatic enzymes
• Synthetic dysfunction: Decreased albumin, prolonged PT/INR

Severity Classification

• Mild: ALT/AST < 3× ULN
• Moderate: ALT/AST 3-5× ULN
• Severe: ALT/AST > 5× ULN or ALT > 2.5× ULN with bilirubin > 2× ULN 1, 2

Diagnostic Workup

Core Investigations (First Line)

• Complete liver panel: ALT, AST, ALP, GGT, bilirubin (total and direct), albumin, PT/INR
• Viral hepatitis screening: HBsAg, anti-HCV antibody (with PCR if positive)
• Autoimmune markers: Anti-mitochondrial antibody, anti-smooth muscle antibody, antinuclear antibody
• Iron studies: Serum ferritin and transferrin saturation
• Immunoglobulins (IgG, IgA, IgM)
• Abdominal ultrasound 1

Extended Investigations (Based on Clinical Context)

• Hepatitis A, D, and E serology
• Ceruloplasmin (Wilson's disease)
• Alpha-1 antitrypsin
• Liver biopsy (if diagnosis remains unclear)
• MRI/MRCP (if biliary pathology suspected) 1

Management Based on Etiology

Drug-Induced Liver Injury

1. Identify and discontinue offending drug if ALT > 3× ULN or if jaundice develops
2. Monitor LFTs more frequently (every 3 days for moderate elevations)
3. Re-evaluate if ALT remains > 3× ULN after drug discontinuation 1, 2

Viral Hepatitis

1. Hepatitis B:

   • Start antiviral therapy according to international guidelines
   • Continue nucleoside antiviral therapy if already on treatment
   • Screen for HBsAg before starting immunosuppressants 1

2. Hepatitis C:

   • Consider direct-acting antivirals (DAAs)
   • Avoid protease inhibitor-containing DAA regimens if on lopinavir-ritonavir 1

Alcoholic Liver Disease

1. Complete abstinence from alcohol
2. Nutritional support
3. Consider corticosteroids for severe alcoholic hepatitis (if no contraindications)

Non-Alcoholic Fatty Liver Disease (NAFLD)

1. Weight loss (7-10% of body weight)
2. Management of metabolic syndrome components (diabetes, hypertension, dyslipidemia)
3. Regular exercise (150 minutes/week of moderate activity)

Autoimmune Hepatitis

1. Corticosteroids ± azathioprine
2. Monitor response with serial LFTs

Monitoring and Follow-up

Frequency of Monitoring

• Mild abnormalities: Every 2-4 weeks initially
• Moderate abnormalities: Weekly until improvement
• Severe abnormalities: Every 2-3 days
• Patients on hepatotoxic medications: Twice weekly 1

Duration of Follow-up

• Continue monitoring until LFTs normalize or stabilize
• If LFTs remain abnormal beyond 8-12 weeks, extended investigations should be performed 1

Special Considerations

Medications Commonly Causing LFT Abnormalities

• Antimicrobials: Isoniazid, ketoconazole, sulfonamides
• Anti-inflammatory: NSAIDs, sulindac
• Cardiovascular: Amiodarone, statins
• Neuropsychiatric: Valproic acid, carbamazepine
• Biologics: TNF inhibitors (adalimumab, infliximab) 3, 2

Thresholds for Medication Discontinuation

• ALT > 3× ULN: Consider temporary discontinuation
• ALT > 5× ULN or jaundice: Immediate discontinuation 3, 2

Pitfalls and Caveats

1. Don't ignore mild LFT abnormalities - they may indicate early liver disease and provide opportunity for intervention 4

2. Don't attribute all LFT abnormalities to medications - always consider other causes including viral hepatitis, autoimmune disease, and metabolic disorders 1

3. Don't forget to screen for viral hepatitis before starting immunosuppressive therapy - reactivation can lead to severe hepatitis 1, 3

4. Don't rely solely on LFTs to rule out liver disease - normal LFTs don't exclude significant liver pathology 5

5. Don't delay investigation - early diagnosis and intervention can prevent progression to advanced liver disease 5

By following this systematic approach to abnormal LFTs, clinicians can effectively diagnose and manage liver disease, potentially preventing progression to more severe liver dysfunction and improving patient outcomes.