What is the frequency of liver function test monitoring in anti-tubercular (antituberculosis) therapy?

From the Guidelines

Liver function tests (LFTs) should be monitored at baseline and only as clinically indicated thereafter, unless there are baseline abnormalities, symptoms consistent with hepatotoxicity develop, or for patients who chronically consume alcohol, take other potentially hepatotoxic medications, or have viral hepatitis or history of liver disease. This approach is supported by the most recent guidelines from the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America, as outlined in the 2016 clinical practice guidelines for the treatment of drug-susceptible tuberculosis 1. The standard first-line antitubercular regimen includes isoniazid, rifampin, pyrazinamide, and ethambutol, all of which can cause drug-induced liver injury.

• Baseline LFTs should be obtained before starting treatment to establish reference values.
• If LFT abnormalities develop (ALT/AST >3 times upper limit of normal with symptoms, or >5 times without symptoms), medication should be temporarily discontinued and reintroduced sequentially once LFTs normalize.
• Patients should be educated about symptoms of hepatotoxicity including nausea, vomiting, abdominal pain, jaundice, dark urine, or fatigue, and instructed to seek immediate medical attention if these occur.
• This monitoring schedule balances the need to detect hepatotoxicity early while maintaining practical clinical follow-up, as drug-induced liver injury typically develops within the first 8 weeks of treatment.
• The 2016 guidelines also recommend assessing adherence and monitoring for improvement in tuberculosis symptoms, as well as development of medication adverse effects 1.
• Additionally, patients with risk factors for hepatotoxicity, such as chronic alcohol consumption or viral hepatitis, should be closely monitored 1.
• It is also important to note that the 2000 guidelines from the American Thoracic Society recommended routine laboratory monitoring during treatment of LTBI for persons whose baseline liver function tests are abnormal and other persons at risk for hepatic disease 1. However, the more recent 2016 guidelines provide a more nuanced approach to monitoring, taking into account the individual patient's risk factors and clinical presentation.

From the FDA Drug Label

Patients with impaired liver function should be given rifampin only in cases of necessity and then under strict medical supervision. In these patients, careful monitoring of liver function should be done prior to therapy and then every 2 to 4 weeks during therapy.

Laboratory Tests Adults treated for tuberculosis with rifampin should have baseline measurements of hepatic enzymes, bilirubin, serum creatinine, a complete blood count, and a platelet count (or estimate). Patients should be seen at least monthly during therapy and should be specifically questioned concerning symptoms associated with adverse reactions.

The frequency of liver function test monitoring in anti-tubercular therapy with rifampicin is:

• Every 2 to 4 weeks for patients with impaired liver function.
• At least monthly for patients without impaired liver function, with specific questioning concerning symptoms associated with adverse reactions. 2 2

From the Research

Liver Function Test Monitoring Frequency

The frequency of liver function test monitoring in anti-tubercular therapy is as follows:

• Patients without high-risk factors should have monthly liver biochemical monitoring 3
• High-risk patients or those using hepatotoxic drugs should be monitored every 2 weeks during the first 2 months of anti-tuberculosis treatment, then monthly 3
• Liver function tests should be obtained at initiation of isoniazid therapy and again during the first two to four months in patients age 35 or older or with a history of alcoholism, liver disease or intravenous drug use 4
• Monitoring of liver function in patients on antituberculous therapy indicated that liver dysfunction most frequently occurs during the first three months of therapy 5
• Scheduled monitoring of liver function could facilitate the early identification of more ATLI cases, thus leading to less liver injury 6
• A uniform policy of liver function testing at 2 weeks is useful for prompt identification of a subgroup who develop early drug-induced liver injury and may offer better specificity in ruling out late drug-induced liver injury 7

Key Considerations

• Risk factors for ATB-DILI include NAT2 slow acetylation genotype, GSTM1 gene variation, advanced age, hepatitis virus infection or concurrent acute/chronic liver disease, HIV infection, malnutrition, and alcohol (ethanol) intake 3
• The American Thoracic Society algorithm had a sensitivity and specificity of 66.7 and 65.6%, respectively, for prediction of early and 22.2% and 63.7% for late drug-induced liver injury 7
• Less than half of all patients who received anti-TB drugs had their liver function monitored regularly 6

Recommendations

• Baseline liver biochemistry, HBsAg, anti-HCV testing, and abdominal imaging should be performed before starting anti-TB treatment 3
• Liver biochemical tests should include at least ALT, AST, ALP, GGT, TBil, DBil, and albumin 3
• Abdominal imaging should be performed for suspected ATB-DILI patients 3