How to manage Anti-Tuberculosis Treatment (ATT)-induced hepatitis in pregnancy?

Management of Anti-Tuberculosis Treatment (ATT)-Induced Hepatitis in Pregnancy

If ATT-induced hepatotoxicity develops during pregnancy, temporarily discontinue all hepatotoxic anti-TB drugs immediately when transaminases exceed 3-5 times the upper limit of normal, then restart therapy cautiously once liver enzymes normalize, prioritizing rifampin and ethambutol as the safest options to resume first. 1, 2

Risk Assessment and Monitoring

Pregnant women face a 9.9-fold increased risk of severe hepatotoxicity during TB treatment compared to non-pregnant women, with 40% of pregnant women developing severe liver toxicity versus only 6% of non-pregnant controls 2. This dramatically elevated risk mandates aggressive monitoring:

• Measure transaminases monthly (or more frequently if any elevation detected) throughout TB treatment in pregnancy 1
• Monitor more closely in women with additional risk factors: age >35, daily alcohol use, chronic liver disease, injection drug use, or minority women in the postpartum period 1
• Fatal hepatotoxicity has been documented in pregnant women on ATT, making vigilant monitoring non-negotiable 2

Immediate Management of Hepatotoxicity

When to Stop Therapy

Temporarily discontinue isoniazid (and other hepatotoxic agents) when transaminases exceed 3-5 times the upper limit of normal 1. The 40% rate of temporary drug withdrawal in pregnant women versus 9.5% in non-pregnant women reflects the severity of this problem 2.

Drug Rechallenge Strategy

After liver enzymes normalize, restart therapy using this algorithmic approach:

1. Rifampin and ethambutol are the safest first-line drugs to restart, as they have the lowest hepatotoxicity risk 1, 3
2. Reintroduce isoniazid last and most cautiously, as it is the primary hepatotoxic culprit 1, 3
3. Add drugs back sequentially (one at a time every 3-7 days) while monitoring transaminases closely 1
4. Pyrazinamide should be avoided entirely during pregnancy due to inadequate teratogenicity data and added hepatotoxicity risk 1, 3

Modified Treatment Regimens for Pregnancy

Standard Regimen Adjustments

The FDA-approved approach for pregnant women with TB specifically excludes pyrazinamide and streptomycin 1:

• Initial regimen: Isoniazid + rifampin + ethambutol for 2 months, then isoniazid + rifampin for 7 months (total 9 months) 1, 3
• Ethambutol should be included unless primary isoniazid resistance is documented to be <4% in the community 1
• Never use streptomycin in pregnancy—it causes congenital deafness in approximately 1 in 6 exposed infants 1, 3

If Hepatotoxicity Recurs

If rechallenge with isoniazid causes recurrent hepatotoxicity:

• Continue with rifampin + ethambutol alone for extended duration (12-18 months) 3
• For drug-resistant TB with hepatotoxicity, ciprofloxacin has the best safety profile among second-line agents in pregnancy 3
• Consultation with a TB expert is mandatory for multidrug-resistant cases 1

Essential Supportive Measures

All pregnant women on isoniazid must receive pyridoxine (vitamin B6) supplementation to prevent peripheral neuropathy and reduce hepatotoxicity risk 3. This is non-negotiable.

Critical Pitfalls to Avoid

• Do not continue hepatotoxic drugs when transaminases are rising—the risk of fulminant hepatic failure and maternal death is real 2
• Do not use pyrazinamide routinely in pregnancy despite its inclusion in standard non-pregnant regimens 1, 3
• Do not delay treatment of active TB due to pregnancy—untreated TB poses greater risk to mother and fetus than the medications 3, 4
• Do not assume standard monitoring intervals are adequate—pregnant women require more frequent assessment given their 10-fold increased hepatotoxicity risk 2

Postpartum Considerations

The postpartum period carries particularly high hepatotoxicity risk in minority women 1. Continue intensive monitoring for at least 3 months postpartum, especially if therapy was interrupted and restarted during pregnancy 2.