Anti-Tuberculosis Therapy-Induced Hepatotoxicity among Ethiopian HIV-Positive and Negative Patients

Getnet Yimer,Beniyam Feleke,Lars Lindquist,Eleni Aklillu,Abraham Aseffa,Getachew Aderaye,Lawrence Yamuah,Wondwossen Amogne,Eyasu Makonnen,Landon Myer

doi:10.1371/journal.pone.0001809

Abstract

BackgroundTo assess and compare the prevalence, severity and prognosis of anti-TB drug induced hepatotoxicity (DIH) in HIV positive and HIV negative tuberculosis (TB) patients in Ethiopia.Methodology/Principal FindingsIn this study, 103 HIV positive and 94 HIV negative TB patients were enrolled. All patients were evaluated for different risk factors and monitored biochemically and clinically for development of DIH. Sub-clinical hepatotoxicity was observed in 17.3% of the patients and 8 out of the 197 (4.1%) developed clinical hepatotoxicity. Seven of the 8 were HIV positive and 2 were positive for HBsAg.Conclusions/SignificanceSub-clinical hepatotoxicity was significantly associated with HIV co-infection (p = 0.002), concomitant drug intake (p = 0.008), and decrease in CD4 count (p = 0.001). Stepwise restarting of anti TB treatment was also successful in almost all the patients who developed clinical DIH. We therefore conclude that anti-TB DIH is a major problem in HIV-associated TB with a decline in immune status and that there is a need for a regular biochemical and clinical follow up for those patients who are at risk.

Highlights

The magnitude of tuberculosis (TB) has increased globally since 1990 due to spread of human immunodeficiency virus (HIV) and population growth[1]
The proportion of patients with anti-tuberculosis therapy induced hepatotoxicity in general has not been studied that often in African patients. We studied this common clinical problem among Ethiopian patients
To effectively study this problem we have excluded patients previously treated with anti-tuberculosis drugs, critically sick patients as assessed by level of consciousness and concomitant illnesses, and Variable HIV status Concomitant drug intake HbsAg Anti-HCV Antibody CD4 count/mm3

Summary

Introduction

The magnitude of tuberculosis (TB) has increased globally since 1990 due to spread of human immunodeficiency virus (HIV) and population growth[1]. The occurrence of drug induced hepatotoxicity (DIH) is difficult to predict, it has been observed that certain patients are at higher risk during the course of anti-TB chemotherapy [10,11,12,13,14,15,16,17]. Various studies have suggested that high alcohol intake, older age, slow acetylation status, pre-existing chronic liver disease, chronic viral infection due to hepatitis B and hepatitis C, HIV infection, advanced tuberculosis, Asian ethnicity, female sex, concomitant administration of enzyme-inducers (e.g. barbiturates and anaesthetic agents), inappropriate use of drugs and poor nutritional status increase the risk of anti-tuberculosis drug induced hepatitis. To assess and compare the prevalence, severity and prognosis of anti-TB drug induced hepatotoxicity (DIH) in HIV positive and HIV negative tuberculosis (TB) patients in Ethiopia

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Conclusion