Anti-tuberculosis (TB) Drug Levels and Hepatotoxicity
Condition: Hepatitis; Tuberculosis
MeSH terms: Tuberculosis
Study type: Observational

Summary: 
      The purpose of this study is to evaluate plasma levels of hepatotoxic anti-tuberculous drugs
      (isoniazid, rifampicin, pyrazinamide plus significant metabolites) among patients on
      antituberculosis treatment (ATT) and compare the same among those who develop drug induced
      hepatitis on follow up versus those who do not.
    

Detailed description: 
      Tuberculosis (TB) is a major health problem in both the developing and developed countries
      because of its resurgence in the immunosuppressed patients. World Health Organization (WHO)
      in 1993 declared tuberculosis to be a 'global emergency' with more than a third of the
      world's population infected. Globally 8.9 million new cases of tuberculosis occur annually,
      of which 1.8 million (20%) occur in India.

      Short-course chemotherapy containing isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA)
      has proved to be highly effective in the treatment of tuberculosis. One of its adverse
      effects is hepatotoxicity. It is the most common side effect leading to interruption of
      therapy. It is associated with mortality of 6-12% if these drugs are continued even after the
      onset of symptoms. Risk of hepatotoxicity is increased when these drugs are combined.

      The time interval between the start of anti-TB drugs and appearance of hepatotoxicity varies
      from 3 to 135 days. In most cases hepatitis is evident within three months of start of
      antituberculosis treatment (ATT).

      The pathogenesis of drug-induced hepatotoxicity (DIH) is still not entirely clear for most
      anti TB drugs including rifampicin. Hypersensitivity is a definite possibility Rifampicin
      induced hepatitis has been postulated to occur as a part of systemic allergic reaction and,
      due to unconjugated hyperbilirubinaemia as a result of competition with bilirubin for uptake
      at hepatocyte plasma membrane. DIH caused by rifampicin occurs earlier as compared to
      isoniazid. While a dose related toxicity may exist, a direct correlation between serum drug
      levels and hepatotoxicity has not been well reported. Thus the clinical relevance of
      therapeutic monitoring of serum rifampicin concentrations in managing DIH is still being
      explored.

      Present study done to observe serum rifampicin, isoniazid, pyrazinamide level in patients on
      ATT and to compare it retrospectively between patients who develop drug induced hepatitis vs
      those who do not.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Subjects: Patients with diagnosis of CatI/CatIII Tuberculosis attending the out-patient
        department of the All India Institute of Medical Sciences, New Delhi, will form the study
        population.

        Cases - those patients who develop DIH while on regular treatment with anti-TB drugs
        Controls - age, sex matched patients who do not develop DIH while on regular treatment with
        anti-TB drugs
      
Biospecimen description: 
      Plasma
    
Keywords: Plasma levels isoniazid rifampicin pyrazinamide