Rechallenge after anti-tuberculosis drug-induced liver injury in a high HIV prevalence cohort

Abstract

Background: There are limited data on the outcomes of rechallenge with anti-tuberculosis therapy (ATT) following anti-tuberculosis drug-induced liver injury (AT-DILI) in a high HIV prevalence setting.Objectives: To describe the outcomes of rechallenge with first-line ATT.Method: Hospitalised participants with AT-DILI who were enrolled into a randomised controlled trial of N-acetylcysteine in Cape Town, South Africa, were followed up until completion of ATT rechallenge. We described rechallenge outcomes, and identified associations with recurrence of liver injury on rechallenge (positive rechallenge).Results: Seventy-nine participants were rechallenged of whom 41 (52%) were female. Mean age was 37 years (standard deviation [s.d.] ±10). Sixty-eight (86%) were HIV-positive, of whom 34 (50%) were on antiretroviral therapy (ART) at time of AT-DILI presentation. Five participants had serious adverse reactions to an aminoglycoside included in the alternate ATT regimen given after first-line ATT interruption: acute kidney injury in three and hearing loss in two. The median time from first-line ATT interruption to start of first-line ATT rechallenge was 13 days (interquartile range [IQR]: 8–18 days). Antiretroviral therapy was interrupted for a median of 32 days (IQR: 17–58) among HIV-positive participants on ART before AT-DILI. Fourteen participants had positive rechallenge (18%). Positive rechallenge was associated with pyrazinamide rechallenge (P = 0.005), female sex (P = 0.039) and first episode of tuberculosis (TB) (P = 0.032).Conclusion: Rechallenge was successful in most of our cohort. Pyrazinamide rechallenge should be carefully considered.

Managing Hepatotoxicity Caused by Anti-tuberculosis Drugs: A Comparative Study of Approaches

“…It is important to note that PZA has been reported to cause more hepatotoxicity compared to other anti-TB drugs. 16 , 17 …”

Management of drug-induced liver injury in people with HIV treated for tuberculosis: 2024 update

“…Studies suggest that between 20% and 90% of adult patients with AT-DILI can be rechallenged with anti-tuberculous therapy without reoccurrence. 29 , 30 Reoccurrence of AT-DILI is strongly associated with the use of PZA as part of the rechallenge regimen. 29 , 31…”

“… 29 , 30 Reoccurrence of AT-DILI is strongly associated with the use of PZA as part of the rechallenge regimen. 29 , 31…”

Clinical standards for the management of adverse effects during treatment for TB

“… 44 , 45 Some guidelines recommend a graded rechallenge (with incremental dosing increase; however, there is no evidence to suggest that this is better than full-dose rechallenge. 27 , 45 , 46 …”