Why are my liver enzymes so high?

Understanding Elevated Liver Enzymes

Elevated liver enzymes require a systematic evaluation as they may indicate significant liver disease, even when the patient appears asymptomatic. The extent of liver enzyme abnormality is not necessarily a guide to clinical significance; rather, the specific analyte that is abnormal and the clinical context determine the significance and necessary follow-up. 1

Patterns of Liver Enzyme Elevation

Hepatocellular Pattern (Elevated ALT/AST)

• Primarily indicates damage to liver cells
• Common causes:
  • Viral hepatitis (A, B, C, E)
  • Non-alcoholic fatty liver disease (NAFLD)
  • Alcoholic liver disease
  • Drug-induced liver injury
  • Autoimmune hepatitis
  • Genetic disorders (hemochromatosis, Wilson's disease)

Cholestatic Pattern (Elevated ALP/GGT)

• Primarily indicates impaired bile flow
• Common causes:
  • Biliary obstruction (gallstones, tumors)
  • Primary biliary cholangitis
  • Primary sclerosing cholangitis
  • Drug-induced cholestasis
  • Infiltrative diseases

Evaluation Approach

1. Determine the pattern of elevation:

   • Hepatocellular (ALT/AST predominant)
   • Cholestatic (ALP/GGT predominant)
   • Mixed pattern

2. Consider magnitude of elevation:

   • Mild elevations (<5× normal): Often NAFLD, alcohol, medications
   • Moderate elevations (5-10× normal): Consider viral hepatitis, autoimmune disease
   • Marked elevations (>10× normal): Acute viral hepatitis, ischemic injury, drug toxicity

3. Standard liver evaluation should include 1:

   • Abdominal ultrasound
   • Hepatitis B surface antigen
   • Hepatitis C antibody (with PCR if positive)
   • Autoimmune markers (anti-mitochondrial, anti-smooth muscle, antinuclear antibodies)
   • Serum immunoglobulins
   • Ferritin and transferrin saturation

Important Clinical Considerations

Duration of Abnormality

Simply repeating abnormal tests without further investigation is not recommended, as many chronic liver diseases (HCV, NAFLD) may have persistent or fluctuating enzyme elevations 1. In one study, 84% of abnormal tests remained abnormal after 1 month, and 75% remained abnormal at 2 years 1.

Normal Enzymes Don't Rule Out Disease

Many patients with significant liver fibrosis may have liver enzymes within normal reference ranges 1. This is particularly important in chronic hepatitis B, where treatment guidelines recommend lower ALT thresholds (>30 U/L for males, >19 U/L for females) 1.

Common Pitfalls

1. Assuming mild elevations are insignificant: The most common causes of chronic liver disease (NAFLD, alcoholic liver disease, hepatitis C) often present with only mild or moderate enzyme elevations 1.

2. Focusing only on the magnitude: The pattern of elevation is more diagnostically useful than the absolute value 2.

3. Overlooking non-hepatic causes: Elevated liver enzymes can result from conditions outside the liver, including muscle disorders (elevated AST), bone disorders (elevated ALP), or medications 3.

4. Ignoring metabolic factors: In patients with elevated liver enzymes, always assess for metabolic syndrome features (obesity, hypertension, diabetes, dyslipidemia) as NAFLD is extremely common 1.

5. Missing alcohol contribution: Even moderate alcohol use may exacerbate underlying liver disease, particularly in those with hepatitis C 1.

Special Situations

Markedly Elevated Enzymes (>1000 U/L)

For patients with ALT >1000 U/L, consider acute viral hepatitis (including hepatitis A and E), cytomegalovirus, ischemic injury, or acute drug toxicity 1, 4.

Elevated CRP and Liver Enzymes

When C-reactive protein is elevated alongside liver enzymes, consider obtaining a routine blood biochemistry panel to evaluate liver enzymes (AST/ALT) which could indicate fatty liver disease 1.

Persistent Unexplained Elevations

For chronic ALT or AST elevations (≥6 months) without an identified cause despite initial evaluation, consider liver biopsy, particularly if there are significant symptoms or evidence of chronic liver disease 1.

Conclusion

When evaluating elevated liver enzymes, a systematic approach based on the pattern of elevation rather than just the magnitude is essential. The clinical context, risk factors, and duration of abnormality should guide the evaluation strategy. Remember that normal liver enzymes do not exclude significant liver disease, and mild elevations should not be dismissed without appropriate investigation.