Serious hepatotoxicity following use of isoniazid preventive therapy in HIV patients in Eritrea

Abstract

WHO information note indicates that isoniazid preventive therapy (IPT) is generally safe with little risk of hepatotoxicity. However, when the policy of IPT for HIV patients was introduced in Eritrea, frequent IPT‐associated hepatotoxicity and fatality have been reported to the Pharmacovigilance Centre. The aim of the study is to assess the causal association of IPT and hepatotoxicity and identify possible risk factors in patients on Highly Active Anti‐retroviral Therapy (HAART). This is a case series assessment of spontaneously reported cases to the Eritrean Pharmacovigilance Centre. Data extracted from VigiFlow (reported between 2014 and 2016) were exported to excel spread sheet for descriptive and qualitative analysis. Naranjo probability scale and Austin Bradford‐Hill criteria were used to assess causality. The P‐Method was used to assess preventability. A total of 31 of cases of hepatotoxicity related to IPT were retrieved. Majority (80.6%) of the cases were marked as “serious” due to life‐threatening situation (n = 15), hospitalization (n = 6), and death (n = 4). Baseline liver function test was normal in 61.3% and hepatitis B and C infections were ruled out in 77.4%. IPT was discontinued in 26 cases and reaction abated in 22 of them. Causality assessment using Austin Bradford‐Hill criteria found that the association was strong, consistent and specific with a plausible temporal relationship and biological mechanism. IPT‐associated hepatotoxicity that led to treatment interruption and death was observed in patients on HAART in Eritrea. Hence, close laboratory monitoring of patients is recommended to minimize the risk.

High Burden of Adverse Drug Reactions to Isoniazid Preventive Therapy in People Living With HIV at 3 Tertiary Hospitals in Uganda: Associated Factors

“…[22][23][24][25] Other studies report the incidence of these ADRs 26 or specifically report IPT-related hepatotoxicity. 6,15 Additional factors may have contributed to the observed differences in the burden of ADRs such as difference in ADR definitions and data collection methods. It is possible that our study overestimated the prevalence of the suspected ADRs due to IPT as a result of patient self-reports.…”

The latent tuberculosis cascade-of-care among people living with HIV: A systematic review and meta-analysis

“…TPT may provide some benefit in high TB incidence settings if all PLHIV are treated without use of LTBI testing [ 86 , 87 ]. However, the use of LTBI tests can identify those most likely to benefit [ 5 ], and treatment without prior LTBI testing might expose PLHIV without TB infection to a nontrivial risk of adverse events [ 88 , 89 ]. Furthermore, the healthcare expenditures for drugs, follow-up visits, and tests including those related to AE, to provide TPT to PLHIV who may not benefit from this could be redirected to strengthening the LTBI cascade-of-care in those (with positive LTBI tests) who will benefit more from TPT.…”

NLRP3 Inflammasome: A Promising Therapeutic Target for Drug-Induced Toxicity

“…Clinical application of the first-line anti-tuberculosis drug isoniazid is also limited due to severe hepatotoxicity (Russom et al, 2018). Apart from the liver histopathological deterioration, isoniazid induced NLRP3 inflammasome activation in a sirtuin 1 (SIRT1)-dependent manner, led to liver injury in rats and L02 cells .…”