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

Management of Transaminitis

The treatment of transaminitis should be primarily directed at the underlying cause, with management strategies tailored based on the severity of elevation and specific etiology. 1

Initial Assessment and Grading

• Transaminitis is graded based on AST/ALT elevation: Grade 1 (>ULN to 3× ULN), Grade 2 (>3× to 5× ULN), Grade 3 (>5× to 20× ULN), and Grade 4 (>20× ULN) 1
• Initial workup should include medication review, viral hepatitis testing, alcohol history assessment, and evaluation for metabolic syndrome 1, 2
• Common causes include nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease, medication-induced injury, viral hepatitis (B and C), and hemochromatosis 2, 3
• Less common causes include autoimmune hepatitis, Wilson disease, alpha-1-antitrypsin deficiency, and extrahepatic conditions (thyroid disorders, celiac disease, muscle disorders) 3

Management Based on Severity

Mild Transaminitis (Grade 1: <3× ULN)

• Close monitoring without specific treatment is recommended with laboratory tests every 1-2 weeks 1
• If NAFLD is suspected, implement lifestyle modifications including weight loss, dietary changes, and increased physical activity 4, 1
• For drug-induced transaminitis, consider monitoring without discontinuation if elevation is <3× ULN 5

Moderate Transaminitis (Grade 2: >3-5× ULN)

• Discontinue potential hepatotoxic medications if medically feasible 1
• Increase monitoring frequency to every 3 days 1
• Consider prednisone 0.5-1 mg/kg/day if no improvement after 3-5 days, particularly if autoimmune etiology is suspected 1
• For drug-induced liver injury with elevations >3× ULN, consider medication discontinuation 5

Severe Transaminitis (Grade 3-4: >5× ULN)

• Urgent hepatology consultation is recommended 1
• Discontinue all hepatotoxic medications 1
• Start methylprednisolone 1-2 mg/kg/day (Grade 3) or 2 mg/kg/day (Grade 4) if autoimmune etiology is suspected 1
• Consider liver biopsy for steroid-refractory cases or diagnostic uncertainty 1
• For Grade 4 transaminitis, immediate hospitalization is recommended, preferably at a liver center 1

Management Based on Specific Etiologies

Autoimmune Hepatitis

• Predniso(lo)ne as initial therapy followed by addition of azathioprine after two weeks is the first-line treatment 4
• Initial prednisolone dosage is typically 0.5-1 mg/kg/day 4
• Azathioprine should be initiated when bilirubin levels are below 6 mg/dl, starting at 50 mg/day and increasing to a maintenance dose of 1-2 mg/kg 4
• Treatment should aim for complete normalization of transaminases and IgG levels 4
• Budesonide (9 mg/day) plus azathioprine may be considered in treatment-naive non-cirrhotic patients with early-stage disease to minimize steroid side effects 4

Drug-Induced Liver Injury

• Identify and discontinue the offending agent 5, 1
• For mild elevations (<3× ULN) during cefoperazone or other antibiotic therapy, continued monitoring may be appropriate 5
• For elevations >3× ULN, consider medication discontinuation 5
• In severe cases (AST/ALT >5× ULN and/or total bilirubin >3× ULN), immediately discontinue the medication and consider hepatology consultation 5

Non-alcoholic Fatty Liver Disease (NAFLD)

• Primary management focuses on lifestyle modifications including weight loss, dietary changes, and increased physical activity 4, 1
• Address metabolic syndrome components including diabetes, hypertension, and dyslipidemia 4, 1
• Regular monitoring of liver enzymes is recommended to assess response to interventions 4

Alcoholic Liver Disease

• Complete abstinence from alcohol is essential 1
• Consider alcohol counseling and support groups 1
• For patients considering gene therapy or other treatments with potential liver effects, alcohol avoidance for at least 6 months before and 1-2 years after treatment is recommended 4

Viral Hepatitis

• For hepatitis B and C, refer to a specialist for antiviral therapy consideration 4, 1
• Monitor liver enzymes regularly during and after treatment 4

Special Considerations

• In patients with acute severe autoimmune hepatitis, treat with high doses of intravenous corticosteroids (≥1 mg/kg) as early as possible; lack of improvement within seven days should lead to consideration for emergency liver transplantation 4
• For HIV-infected patients with transaminitis, consider antiretroviral therapy adjustments and evaluate for coinfections with hepatitis viruses 4, 6
• In patients with failure to respond to treatment for autoimmune hepatitis, reconsider diagnosis or evaluate adherence to treatment 4
• For asymptomatic patients with mild transaminitis and no advanced fibrosis, treatment may be optional, but regular monitoring (every 3 months) of ALT and IgG levels is essential, with follow-up liver biopsy if increases occur 4

Monitoring and Follow-up

• For mild transaminitis, monitor liver function tests every 1-2 weeks initially 1
• For moderate to severe transaminitis, more frequent monitoring is required 1
• Complete normalization of transaminases and IgG levels should be the aim of treatment in autoimmune hepatitis 4
• Persistent elevations of transaminases in autoimmune hepatitis predict relapse after treatment withdrawal, activity on liver biopsy, progression to cirrhosis, and poor outcome 4