Assessing Antibiotic Induced Liver Injury for Stratification of Tuberculosis Patients (ALISTER)

Primary Outcome Measures:

• Anti-tuberculosis drug-induced liver injury [ Time Frame: Upto 3 years, or until the end of TB treatment ]

  Anti-tuberculosis drug-induced liver injury defined as ALT elevation more than three times the ULN in the presence of hepatitis symptoms and/or jaundice, or five times the ULN in the absence of symptoms.

  This is a 'proof of concept' study to determine whether a panel of biomarkers are elevated in tuberculosis patients who develop anti-tuberculosis drug-induced liver injury.

  
  

To improve patient stratification, the investigators have developed a panel of novel circulating liver specific and mechanistic biomarkers that report early acute liver injury. Such biomarkers are needed as current early biomarkers of liver injury lack sensitivity and specificity. The panel of biomarkers either have enhanced liver specificity or provide mechanistic insights. Currently, antituberculosis drug-induced liver injury (ATDILI) is the most frequent side-effect of anti-tuberculosis therapy and this hinders the effective treatment of TB, as it means that treatment regimens are not completed. At present, the risk of ATDILI means that monitoring of liver function is required, with levels of ALT measured monthly. If levels of ALT rise to 2-5x the upper limit of normal levels (ULN) and the patient is unwell the frequency of monitoring is increased to biweekly monitoring. Antibiotic therapy is only changed if levels of ALT remain greater than 3xULN, the patient continues to display symptoms and there is a positive causality assessment that the anti-tuberculosis drugs are causing ATDILI. This project will recruit patients taking antituberculosis drugs and determine the diagnostic and prognostic value of the biomarker panel, in relation to liver injury as a result of anti-tuberculosis therapy.