How to treat elevated Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels?

Treatment of Elevated AST and ALT Levels

The treatment of elevated AST and ALT levels should be directed at the underlying cause, with initial evaluation focusing on common etiologies such as nonalcoholic fatty liver disease, alcoholic liver disease, viral hepatitis, and medication-induced liver injury. 1, 2

Initial Evaluation

• Obtain a detailed history focusing on alcohol consumption (quantity, frequency, duration), medications (including over-the-counter drugs, vitamins, herbs), risk factors for viral hepatitis, and family history of liver disease 1
• Assess for metabolic syndrome components (waist circumference, blood pressure, fasting lipids, fasting glucose/A1C) as nonalcoholic fatty liver disease is a common cause of elevated transaminases 2
• Note the pattern of elevation: AST/ALT ratio >2 suggests alcoholic liver disease, while AST/ALT ratio <1 is more common in nonalcoholic fatty liver disease 1
• Evaluate the degree of elevation - mild elevations (<5 times upper limit of normal) are common and have a different differential than marked elevations 1, 2

Diagnostic Workup

• Initial laboratory tests should include complete blood count with platelets, serum albumin, bilirubin, prothrombin time, iron studies (serum iron, total iron-binding capacity, ferritin), hepatitis C antibody, and hepatitis B surface antigen 1, 2
• Consider testing for less common causes if initial evaluation is unremarkable: autoimmune hepatitis, hereditary hemochromatosis, Wilson's disease, alpha-1-antitrypsin deficiency 1
• Evaluate for non-hepatic causes of elevated transaminases including thyroid disorders, celiac disease, muscle disorders, and hemolysis 3, 4
• Abdominal ultrasonography should be considered if the elevation persists despite lifestyle modifications 1

Treatment Approaches by Etiology

Nonalcoholic Fatty Liver Disease (NAFLD)

• First-line treatment is lifestyle modification with weight loss (if overweight/obese), increased physical activity, and dietary changes 1
• Target weight loss of 7-10% of body weight to improve liver histology 1
• Monitor transaminases every 3-6 months to assess response to intervention 1
• Consider referral to gastroenterology for persistently elevated or worsening transaminases 1

Alcoholic Liver Disease

• Complete abstinence from alcohol is the cornerstone of treatment 1
• Consider alcohol rehabilitation programs and support groups 1
• Monitor GGT levels, which typically recover slowly following abstinence 1

Viral Hepatitis

• For chronic hepatitis B with active viral replication and elevated transaminases, antiviral therapy is indicated 1, 5
• For hepatitis B, entecavir 0.5 mg once daily (treatment-naïve) or 1 mg once daily (lamivudine-refractory) is recommended for patients with evidence of active viral replication and persistent elevations in serum aminotransferases 5
• Monitor hepatic function closely for at least several months after discontinuation of antiviral therapy due to risk of severe acute exacerbations 5

Drug-Induced Liver Injury

• Discontinue the suspected offending medication when possible 1
• Monitor liver tests until resolution 1
• Avoid reintroduction of the suspected medication 1

Immune-Mediated Liver Injury (e.g., from immune checkpoint inhibitors)

• For ALT ≥3× ULN (or ≥2× baseline if baseline was elevated), evaluate for possible causes 1
• If immune-mediated liver injury is suspected, consider interruption/discontinuation of the causative agent and initiation of immunosuppressive therapy with corticosteroids 1

Special Considerations

• In patients with diabetes, routine screening for NAFLD by measuring AST and ALT should be performed annually 1
• In children and adolescents with type 2 diabetes, evaluation for nonalcoholic fatty liver disease (by measuring AST and ALT) should be done at diagnosis and annually thereafter 1
• For patients with glycogen storage disease and other metabolic disorders, specific treatment protocols should be followed 1

When to Refer to Specialist Care

• Persistent elevation of transaminases (>6 months) despite appropriate initial management 1
• Evidence of advanced liver disease (decreased albumin, prolonged prothrombin time, thrombocytopenia) 1
• Marked elevation of transaminases (>5 times upper limit of normal) 1
• Suspected autoimmune hepatitis, Wilson's disease, or other rare liver diseases 1
• Patients with chronic viral hepatitis requiring antiviral therapy 1

Monitoring Response to Treatment

• Follow transaminase levels at regular intervals (typically every 3-6 months) to assess response to intervention 1
• An AST/ALT ratio ≤0.4 following severe hepatotoxicity appears to be highly predictive of recovery 6
• In alcoholic liver disease, normalization of transaminases with abstinence supports the diagnosis 1