Management of DR-TB ADR: Hepatitis

Hepatitis is a common adverse drug reaction caused by some Drug-resistance TB (DR-TB) drugs. It is monitored by measuring the Alanine transaminase (ALT) and Aspartate aminotransferase (AST) levels.

If there is jaundice (yellowing of the skin or eyes), field-level health care workers must immediately refer the patient to the nearest higher health centres - District/ Nodal DR-TB Centre/ Sub-district or district hospital, medical college hospitals, etc.

Suspected agent(s): Pyrazinamide (Z), Isoniazid (H), Rifampicin (R), Ethionamide (Eto), P-aminosalicylic Acid (PAS), Bedaquiline (Bdq)

Suggested Management Strategies

• In cases where the patient is very sick, i.e., having meningitis and sputum smear is grade 3+, administer Anti-TB Treatment (ATT), e.g., Streptomycin, Fluoroquinolone (FQ) and Cycloserine (Cs). 
• Where the patient is not seriously ill and one can wait, the introduction of ATT can be done once enzyme levels are near normal.
• If enzymes are more than five times the upper limit of normal, stop all hepatotoxic drugs and continue with at least three non-hepatotoxic medications (for example, the injectable agent, FQ and Cs). If hepatitis worsens or does not resolve with the three-drug regimen, then stop all drugs.
• If hepatitis worsens or does not resolve with the three-drug regimen, then stop all drugs.
• Eliminate other potential causes of hepatitis (viral hepatitis and alcohol-induced hepatitis being the two most common causes) and treat any that are identified.
• Once enzyme level improves, reintroduce remaining drugs, one at a time with the least hepatotoxic agents first, while monitoring liver function by testing enzymes every three days. 
• If the most likely agent causing hepatitis is not essential, consider not reintroducing it.

Points to Note

• Any history of previous drug-induced hepatitis should be carefully analysed to determine the most likely causative agent(s); these drugs should be avoided in future regimens.
• Viral serology should be done to rule out other aetiologies of hepatitis if available, especially, for hepatitis A, B and C.
• Alcohol use should be investigated and addressed if found.
• Generally, hepatitis due to medications resolves upon discontinuation of the suspected drug.

Resources

• Guidelines for Programmatic Management of Drug-resistant Tuberculosis in India, March 2021.
• Technical and Operational Guidelines for TB in India, 2016.

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