Which liver enzymes are elevated in rifampicin (Rifampin)-induced liver injury?

Rifampicin-Induced Liver Injury Primarily Elevates Alanine Aminotransferase (ALT)

In rifampicin-induced liver injury, alanine aminotransferase (ALT) is the primary liver enzyme that becomes elevated, typically showing a hepatocellular pattern of injury. 1

Patterns of Liver Enzyme Elevation in Rifampicin-Induced Liver Injury

• Rifampicin primarily causes hepatocellular liver injury characterized by predominant elevation of ALT, often exceeding 5× upper limit of normal (ULN) 1, 2
• The FDA drug label specifically warns about hepatotoxicity of "hepatocellular, cholestatic, and mixed patterns" with rifampicin, with ALT elevation being the most common marker 1
• The pattern of liver injury is determined by the R value, where R = (ALT/ULN)/(ALP/ULN):
  • R ≥5 indicates hepatocellular injury (most common with rifampicin)
  • R <2 indicates cholestatic injury
  • R between 2-5 indicates mixed hepatocellular-cholestatic injury 2

Other Liver Enzymes in Rifampicin-Induced Liver Injury

• Aspartate aminotransferase (AST) is also commonly elevated, but typically to a lesser extent than ALT 3, 4
• Alkaline phosphatase (ALP) may show mild to moderate elevation in mixed or cholestatic patterns of rifampicin-induced liver injury 1, 2
• Gamma-glutamyl transferase (GGT) may be elevated, particularly in cholestatic or mixed patterns of injury 5
• Total bilirubin may increase in severe cases, with elevation >2× ULN alongside ALT ≥3× ULN indicating more severe hepatocellular injury (Hy's Law) 1, 2

Monitoring Recommendations for Rifampicin-Induced Liver Injury

• The FDA drug label recommends monitoring liver function tests prior to therapy and then every 2-4 weeks during therapy in patients with impaired liver function 1
• Monitoring should include ALT, AST, ALP, GGT, and total bilirubin 2, 1
• Discontinuation of rifampicin is recommended if signs of hepatic damage occur or worsen 1

Special Considerations

• Rifampicin has been associated with increased risk of hepatotoxicity in patients with primary biliary cholangitis (PBC) when used to treat pruritus 2
• Patients with underlying chronic liver disease who develop drug-induced liver injury may have increased morbidity and mortality compared to those with healthy livers 2
• Rifampicin-induced liver injury is rare but more likely in patients with baseline hepatic dysfunction, requiring increased vigilance in monitoring transaminases in these patients 3

Common Pitfalls and Caveats

• Isolated elevation of GGT without other liver enzyme abnormalities is a poor indicator of liver injury and insufficient to qualify as drug-induced liver injury 2
• When evaluating liver enzyme elevations in patients on rifampicin, it's important to rule out other causes of liver injury, including viral hepatitis, autoimmune hepatitis, and other medications 6
• Rifampicin can cause transient abnormalities in liver function tests, including elevation in serum bilirubin, alkaline phosphatase, and serum transaminases 1
• The risk of hepatotoxicity may be increased when rifampicin is given with other hepatotoxic agents 1