title: Tuberculous Drug-induced Liver Injury and Treatment Re-challenge in Human Immunodeficiency Virus Co-infection.
abstract: BACKGROUND
  Tuberculosis drug-induced liver injury (TB-DILI) is the most common adverse event necessitating therapy interruption. The optimal re-challenge strategy for antituberculous therapy (ATT) remains unclear, especially in human immunodeficiency virus (HIV) co-infected individuals in high-prevalence settings such as South Africa.
  
  
  OBJECTIVE
  To determine the incidence of and risk factors for the recurrence of TB-DILI with different ATT re-challenge strategies.
  
  
  METHODS
  We conducted a retrospective chart review of patients managed for TB-DILI from 2005 to 2013 at King Edward VIII Hospital in Durban, South Africa. Relevant clinical and laboratory data at the presentation of TB-DILI, time to recovery of liver function, method of ATT re-challenge and outcome of re-challenge were documented.
  
  
  RESULTS
  1016 charts were reviewed, and 53 individuals with TB-DILI (48 HIV-co-infected) were identified. Following discontinuation of ATT, the median time to alanine aminotransferase normalization was 28 days (interquartile range 13-43). Forty-two subjects were re-challenged (30 regimen re-challenges and 12 step-wise re-challenges). 5 (12%) cases of recurrent TB-DILI were noted. Recurrences were not associated with the method of re-challenge.
  
  
  CONCLUSIONS
  Based on the data available, it appears that full ATT can be safely restarted in the majority of subjects with a recurrence of DILI occurring in about 12% of subjects. The method of re-challenge did not appear to impact on the risk of recurrence. Ideally, a prospective randomized trial is needed to determine the best method of re-challenge.
authors.affiliation: Department of Medicine, Divisions of Infectious Diseases/Chronic Viral Illness Service and Lachine Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Cecilia T
authors.initials: CT
authors.lastname: Costiniuk
authors.affiliation: Department of Infectious Diseases, Division of Internal Medicine, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; King Edward VIII Hospital, Department of Infectious Diseases, Congella, Durban, South Africa.
authors.forename: Bernadett I
authors.initials: BI
authors.lastname: Gosnell
authors.affiliation: Department of Infectious Diseases, Division of Internal Medicine, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; King Edward VIII Hospital, Department of Infectious Diseases, Congella, Durban, South Africa.
authors.forename: Thandekile C
authors.initials: TC
authors.lastname: Manzini
authors.affiliation: Department of Infectious Diseases, Division of Internal Medicine, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; King Edward VIII Hospital, Department of Infectious Diseases, Congella, Durban, South Africa.
authors.forename: Camille N
authors.initials: CN
authors.lastname: Du Plessis
authors.affiliation: Department of Infectious Diseases, Division of Internal Medicine, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; King Edward VIII Hospital, Department of Infectious Diseases, Congella, Durban, South Africa.
authors.forename: Mahomed Yunus S
authors.initials: MY
authors.lastname: Moosa
keywords: Anti-tuberculous treatment re-challenge; drug-induced liver injury; hepatotoxicity; human immunodeficiency virus; tuberculosis