How does tuberculosis (TB) affect the liver?

Tuberculosis Effects on the Liver

Tuberculosis can affect the liver in three main forms: diffuse hepatic involvement with pulmonary/miliary TB, granulomatous hepatitis, and focal tuberculoma or abscess, potentially causing liver dysfunction that requires careful monitoring and management of anti-TB medications. 1

Forms of Hepatic Tuberculosis

• Diffuse hepatic involvement is the most common form, typically seen alongside pulmonary or miliary tuberculosis 1
• Granulomatous hepatitis is the second form, presenting as an extrapulmonary manifestation of TB 1
• Focal tuberculoma or abscess is the rarest form, presenting as localized lesions in the liver 1

Liver Function Abnormalities in TB

• TB infection itself can cause modest elevations of hepatic transaminases (ALT/AST) even before treatment begins 2
• Anti-tuberculosis drugs commonly cause derangement of hepatic function to varying degrees 3
• Drug-induced liver injury (DILI) is the most frequent serious adverse reaction to first-line TB drugs 4
• Hepatotoxicity from TB medications most frequently occurs during the first three months of therapy 3

Risk Factors for TB-Related Liver Injury

• Pre-existing liver disease increases risk of hepatotoxicity during TB treatment 2
• Poor nutritional status and hypoalbuminemia are significant risk factors 5, 6
• Female gender appears to have higher risk (OR 4.2) of developing hepatotoxicity 5
• Concomitant use of other hepatotoxic medications significantly increases risk 6
• HIV co-infection requires additional monitoring due to increased hepatotoxicity risk 2

Management of TB Treatment with Liver Involvement

Monitoring Recommendations

• Liver function tests (LFTs) should be performed before starting TB treatment 2
• Regular monitoring of LFTs (weekly for two weeks, then biweekly for first two months) is required for patients with known chronic liver disease 2
• For patients without pre-existing liver disease, routine LFTs are not required unless symptoms develop 2
• Patients should be advised about symptoms of liver dysfunction (malaise, nausea, jaundice) and instructed to stop medication and seek medical attention if these occur 2

Management of Hepatotoxicity

• If AST/ALT rises to five times the upper limit of normal or if bilirubin rises, hepatotoxic drugs (isoniazid, rifampin, pyrazinamide) should be stopped immediately 2
• If the patient is not acutely ill and TB is non-infectious, treatment can be paused until liver function normalizes 2
• For ill patients or those with infectious TB, alternative non-hepatotoxic drugs (streptomycin and ethambutol) should be used until liver function normalizes 2
• Once liver function returns to normal, drugs can be reintroduced sequentially (isoniazid, then rifampin, then pyrazinamide) with careful monitoring 2

Special Considerations

• Patients with underlying chronic liver disease can still receive TB treatment but require modified regimens with fewer hepatotoxic drugs 1
• Alcohol consumption should be avoided during TB treatment due to increased hepatotoxicity risk 2
• Rifampin can cause brownish-red or orange discoloration of body fluids including urine, which should not be confused with jaundice 7
• In severe hepatic disease, rifampin overdose can lead to unconsciousness and requires intensive supportive care 7

Treatment Adaptation for Liver Disease

• Isoniazid (H), rifampin (R), and pyrazinamide (Z) are predominantly metabolized by the liver and require careful monitoring in patients with liver disease 2
• Streptomycin (S) and ethambutol (E) are less hepatotoxic and can be used as alternative agents when liver function is compromised 2
• The principle of TB treatment in patients with liver disease is to closely monitor for signs of worsening liver function and adjust the number of hepatotoxic drugs according to severity of underlying liver disease 1