When should liver function tests (LFTs) be performed in a patient with a history of liver disease or at increased risk of hepatotoxicity who is taking anti-tubercular treatment?

Timing of Liver Function Tests in High-Risk Patients on Anti-Tubercular Treatment

Patients with pre-existing liver disease or hepatotoxicity risk factors require baseline liver function tests (AST, ALT, bilirubin, alkaline phosphatase) before starting anti-TB treatment, followed by routine monitoring during therapy—specifically at 2,4, and 8 weeks if on rifampin-pyrazinamide regimens, or monthly if on isoniazid-based regimens. 1

Baseline Testing Requirements

All high-risk patients must have baseline LFTs before initiating treatment. High-risk categories include: 1, 2

• HIV-infected patients 1
• Pregnant women and those within 3 months postpartum 1
• Persons with chronic liver disease (hepatitis B or C, alcoholic hepatitis, cirrhosis) 1
• Regular alcohol users 1
• Patients taking other hepatotoxic medications 1

Baseline testing should include AST (SGOT), ALT (SGPT), bilirubin, and alkaline phosphatase. 1, 2

Monitoring Schedule During Treatment

For Rifampin-Pyrazinamide Regimens:

Monitor at weeks 2,4, and 8 with clinical evaluation and LFTs. 1 This intensive schedule reflects the higher hepatotoxicity risk of this combination, particularly the early rifampin-enhanced isoniazid toxicity (within 15 days) and late pyrazinamide toxicity (after 1 month). 3

For Isoniazid-Based or Rifampin-Alone Regimens:

Monitor at least monthly with clinical evaluation. 1 For patients with baseline LFT abnormalities or chronic liver disease, obtain LFTs weekly for the first 2 weeks, then biweekly for the first 2 months. 4, 3

Enhanced Monitoring Protocol:

For patients with chronic liver disease specifically, one approach recommends: 3

• Twice weekly LFTs during the first 2 weeks
• Every 2 weeks during months 1-2
• Monthly thereafter

Clinical Monitoring at Each Visit

Every monitoring visit should include: 1, 4

• Questioning about hepatotoxicity symptoms: nausea, vomiting, abdominal pain, jaundice, dark urine, light-colored stools, fever, malaise 1, 4
• Brief physical examination checking for jaundice and hepatomegaly 1
• Patient education about stopping medications immediately if symptoms develop 4

Critical Thresholds for Action

Stop all hepatotoxic TB drugs (rifampin, isoniazid, pyrazinamide) immediately if: 4, 2

• ALT/AST ≥5× upper limit of normal in asymptomatic patients 1, 4
• ALT/AST ≥3× upper limit of normal WITH hepatitis symptoms 1, 4
• ANY elevation in bilirubin above normal range, regardless of transaminase levels 4

Special Considerations for Patients with Pre-existing Liver Disease

In patients with decompensated cirrhosis or advanced liver dysfunction (Child-Turcotte-Pugh score ≥8), limit the number of hepatotoxic drugs used. 5 Consider:

• CTP ≤7: Maximum 2 hepatotoxic drugs (rifampin + isoniazid) 5
• CTP 8-10: Maximum 1 hepatotoxic drug (rifampin OR isoniazid) 5
• CTP ≥11: Avoid all hepatotoxic drugs; use alternative regimens 5

Critical Pitfalls to Avoid

• Do not assume routine monitoring is unnecessary in high-risk patients even if baseline LFTs are normal—these patients require scheduled monitoring throughout treatment 1, 2
• Do not ignore symptom development between scheduled visits—instruct patients to seek immediate evaluation and obtain LFTs if any hepatotoxicity symptoms occur 4, 2
• Do not attribute all transaminase elevations to drugs—exclude viral hepatitis, biliary disease, alcohol, acetaminophen, and other causes 4
• Do not continue treatment if bilirubin rises—any bilirubin elevation mandates immediate cessation of hepatotoxic drugs 4
• Do not use pyrazinamide in patients with baseline liver abnormalities—the risk of severe late hepatotoxicity with poor prognosis is too high 3