title: Baseline abnormal liver function tests are more important than age in the development of isoniazid-induced hepatoxicity for patients receiving preventive therapy for latent tuberculosis infection.
abstract: BACKGROUND
  One of the cornerstones of Australia's public health programmes to eliminate tuberculosis (TB) is the identification and treatment of latent tuberculosis infection (LTBI).
  
  
  OBJECTIVE
  The main aim of this study is to determine the demographics, compliance, completion rates and adverse events of patients on preventive therapy (PT) for LTBI at our institution. The secondary aim is to determine the rates of isoniazid (INH) hepatotoxicity and identify any contributory factors.
  
  
  METHODS
  The method used was an audit using medical records of 100 consecutive patients (2010-2014) treated with PT for LTBI.
  
  
  RESULTS
  Seventy-two patients with confirmed LTBI started 9 months of INH and 22 started 4 months of rifampicin (RIF). The median age was 30 years. Half the patients were born in high TB-prevalence countries. Fifty-six per cent were contacts of index cases with confirmed TB, and 26% were pre-immunosuppression. Seventy-seven per cent completed PT with adequate compliance. Thirty-three per cent on INH and 23% on RIF experienced some liver function test (LFT) abnormality while on treatment. INH was ceased in 3% due to asymptomatic hepatic dysfunction (transaminases >5x upper limit of normal). No patients had permanent liver damage. Significant risk factors for liver dysfunction during PT were risk factors for liver disease (χ(3)(2) = 8.7; P = 0.03) or abnormal pre-therapy LFT (χ(3)(2)= 22.4; P < 0.001). No patients developed active TB.
  
  
  CONCLUSIONS
  The completion rate of 77% and rate of INH-induced hepatic dysfunction of 3% is comparable with the literature. We found no age association with the risk of INH-induced hepatic dysfunction; however, there was a significant and linear association with the degree of liver function abnormality during INH therapy and the presence of abnormal baseline LFT. Routine LFT monitoring allowed early cessation of INH in those with significant but asymptomatic hepatitis who did not meet criteria for ATS/CDC LFT monitoring.
authors.affiliation: Department of Respiratory Medicine, Prince of Wales Hospital, Sydney, New South Wales, Australia.
authors.forename: E L
authors.initials: EL
authors.lastname: Gray
authors.affiliation: Department of Respiratory Medicine, Prince of Wales Hospital, Sydney, New South Wales, Australia.
authors.forename: H F
authors.initials: HF
authors.lastname: Goldberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000175:diagnosis; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects*; D055985:Latent Tuberculosis / Q000097:blood* / Q000175:diagnosis / Q000517:prevention & control*; D008111:Liver Function Tests; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid
keywords: drug-induced liver injury; isoniazid; latent tuberculosis; patient compliance; rifampicin