Diagnostic Workup for Elevated Liver Enzymes
The recommended laboratory workup for a patient with elevated liver enzymes should include a comprehensive liver panel, viral hepatitis screening, autoimmune markers, and abdominal ultrasound to determine the underlying cause and assess for liver damage. 1
Initial Pattern Recognition and Assessment
- Determine the pattern of liver enzyme elevation: hepatocellular (predominant ALT/AST elevation), cholestatic (predominant ALP/GGT elevation), or mixed pattern 1
- Categorize severity of elevation: mild to moderate (<3× ULN) or severe (>3× ULN) 1
- Note that an ALT:AST ratio >1 typically suggests non-alcoholic liver diseases, while AST:ALT ratio >1 is more common in alcoholic liver disease 1, 2
Core Laboratory Panel
- Complete blood count with platelets (to assess for thrombocytopenia which may suggest portal hypertension) 3, 1
- Comprehensive metabolic panel including liver enzymes (ALT, AST, ALP), bilirubin (total and direct), albumin, and creatinine 3, 1
- Prothrombin time/INR (to assess synthetic function) 3, 1
- Viral hepatitis screen: Hepatitis B surface antigen, Hepatitis C antibody (with follow-on PCR if positive) 3, 1
- Autoimmune markers: IgG levels, anti-nuclear antibody (ANA), anti-smooth muscle antibody (ASMA), anti-mitochondrial antibody (AMA) 3, 1
- Iron studies: serum ferritin and transferrin saturation (to assess for hemochromatosis) 3, 1
- Consider Hepatitis A and E testing for marked ALT elevations (>1000 U/L) 3, 1
Imaging
- Abdominal ultrasound to assess liver parenchyma, biliary tract, and for signs of cirrhosis or focal lesions 3, 1
- Consider MRI/MRCP if primary sclerosing cholangitis is suspected, especially with inflammatory bowel disease history and cholestatic pattern 3, 1
Additional Testing Based on Clinical Context
- For suspected NAFLD: Calculate non-invasive fibrosis scores (FIB-4, NAFLD Fibrosis Score) 3, 1
- For suspected alcoholic liver disease: Check GGT, AST/ALT ratio >2 is suggestive 1, 2
- For suspected autoimmune hepatitis: Comprehensive autoimmune panel 1
- For suspected hemochromatosis (elevated ferritin and transferrin saturation >45%): Consider genetic testing 3, 1
- For HIV-infected patients: Test for both HBsAg and anti-HBc, and if either is positive, test for HBV DNA 3
Specific Considerations for Different Patient Populations
- In patients with risk factors for NAFLD (obesity, diabetes, dyslipidemia): Focus on metabolic parameters and fibrosis assessment 3, 2
- In patients with history of alcohol use: Detailed alcohol history using validated tools (AUDIT-C) 1, 2
- In patients on medications: Thorough medication review for potential drug-induced liver injury 1, 2
- In children: Include alpha-1-antitrypsin level, caeruloplasmin (age >3 years), and anti-liver kidney microsomal antibody 3
Monitoring and Follow-up
- For mild elevations (<3× ULN) without clear cause: Repeat testing in 2-5 days to establish trend 1, 2
- If initial workup is negative and enzymes remain mildly elevated: Repeat core laboratory panel in 2-4 weeks 4, 2
- For medication-related elevations: Consider modification or discontinuation of suspected hepatotoxic medications 1, 2
Referral Criteria
- ALT >8× ULN or >5× baseline in those with elevated baseline 1
- ALT >3× ULN with total bilirubin >2× ULN (meets Hy's Law criteria) 1
- Evidence of synthetic dysfunction (elevated INR, low albumin) 1, 2
- Persistent elevation >2× ULN after 3 months despite addressing modifiable factors 1, 2
- Imaging suggesting advanced fibrosis, cirrhosis, or focal lesions 1, 2
Common Pitfalls to Avoid
- Don't simply repeat the same panel of tests without a diagnostic plan 1
- Don't ignore mild elevations, as 84% remain abnormal on retesting after 1 month 1, 4
- Don't miss hepatitis B or C infection, which may be asymptomatic but require treatment 3, 1
- Don't overlook the potential relationship between liver function and other factors like medications, alcohol use, and obesity 1, 2