Antituberculosis drug‐induced hepatotoxicity is uncommon in Tanzanian hospitalized pulmonary TB patients

Tostmann, Alma; Boogaard, Jossy van den; Semvua, Hadija; Kisonga, Riziki; Kibiki, Gibson; Aarnoutse, Rob E.; Boeree, Martin J.

doi:10.1111/j.1365-3156.2009.02449.x

Cited by 11 publications

(10 citation statements)

References 20 publications

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“…reported an increased risk for hepatotoxicity secondary to TB therapy among hospitalized HIV‐infected patients; however, the effect of concomitant ART could not be assessed in this retrospective study of hospital records . In studies from other African settings, hepatotoxicity from TB therapy has been reported to be low . In Tanzania, the prevalence of hepatotoxicity was only 0.9% at 2 months of TB therapy .…”

Section: Discussionmentioning

confidence: 66%

Elevated alanine aminotransferase in antiretroviral‐naïve HIV‐infected African patients: magnitude and risk factors

et al. 2012

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Background Alanine aminotransferase (ALT) is commonly used to measure liver injury in resource limited settings. Elevations in ALT are predictive of increased mortality from liver disease and may influence choice of first line antiretroviral therapy (ART). Methods A cross-sectional analysis of the prevalence and predictors of elevated ALT (defined as > 40 IU/L) was conducted. ART naïve, HIV-infected adults with a baseline ALT who were enrolled in any of the 18 HIV care and Treatment clinics in Dar es Salaam, Tanzania November 2004 and December 2009 were included. Median values were calculated and log-binomial regression models were used to examine predictors of elevated ALT. Results During the study period, 41,891 adults had a baseline ALT performed. The prevalence of ALT greater than 40 IU/L, 120 IU/L and 200 IU/L was 13%, 1% and 0.3%, respectively. In multivariate analyses, male sex, CD4+ T lymphocyte count <200 cells/mm3 and higher WHO clinical stages were associated with a significantly higher risk of ALT >40 IU/L (all p <0.01). Hypertryglyceridemia, hyperglycemia and hepatitis B co-infection (HbsAg+) were significantly associated with higher risk of elevated ALT. Pregnancy, anemia, LDL>130 mg/dl and current TB treatment were associated with significantly reduced risk for elevated ALT. Conclusion In this HIV-infected, ART-naïve, Tanzanian population extreme elevations in ALT were infrequent but minor elevations were not uncommon. Antiretrovirals with potentially hepatotoxic side effects should be initiated with caution in males, patients with hepatitis B co-infection, advanced immunosuppression and components of the metabolic syndrome.

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Section: Discussionmentioning

confidence: 66%

Elevated alanine aminotransferase in antiretroviral‐naïve HIV‐infected African patients: magnitude and risk factors

et al. 2012

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“…Unexpectedly low (2%) anti-tuberculosis drug-induced hepatotoxicity was also reported in HIV-infected pulmonary tuberculosis patients from Malawi [38]. Antituberculosis drug-induced hepatotoxicity is reported to be uncommon (1%) in Tanzanian hospitalized pulmonary TB patients [39]. In contrast higher incidence of rifampicin based anti-TB DILI (17%) [28], efavirenz based HAART associated DILI (15%) [29] and concomitant HAART and anti-TB DILI (30%) from Ethiopia is reported [30].…”

Section: Discussionmentioning

confidence: 96%

Liver Enzyme Abnormalities and Associated Risk Factors in HIV Patients on Efavirenz-Based HAART with or without Tuberculosis Co-Infection in Tanzania

et al. 2012

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ObjectivesTo investigate the timing, incidence, clinical presentation, pharmacokinetics and pharmacogenetic predictors for antiretroviral and anti-tuberculosis drug induced liver injury (DILI) in HIV patients with or without TB co-infection.Methods and FindingsA total of 473 treatment naïve HIV patients (253 HIV only and 220 with HIV-TB co-infection) were enrolled prospectively. Plasma efavirenz concentration and CYP2B6*6, CYP3A5*3, *6 and *7, ABCB1 3435C/T and SLCO1B1 genotypes were determined. Demographic, clinical and laboratory data were collected at baseline and up to 48 weeks of antiretroviral therapy. DILI case definition was according to Council for International Organizations of Medical Sciences (CIOMS). Incidence of DILI and identification of predictors was evaluated using Cox Proportional Hazards Model. The overall incidence of DILI was 7.8% (8.3 per 1000 person-week), being non-significantly higher among patients receiving concomitant anti-TB and HAART (10.0%, 10.7per 1000 person-week) than those receiving HAART alone (5.9%, 6.3 per 1000 person-week). Frequency of CYP2B6*6 allele (p = 0.03) and CYP2B6*6/*6 genotype (p = 0.06) was significantly higher in patients with DILI than those without. Multivariate cox regression model indicated that CYP2B6*6/*6 genotype and anti-HCV IgG antibody positive as significant predictors of DILI. Median time to DILI was 2 weeks after HAART initiation and no DILI onset was observed after 12 weeks. No severe DILI was seen and the gain in CD4 was similar in patients with or without DILI.ConclusionsAntiretroviral and anti-tuberculosis DILI does occur in our setting, presenting early following HAART initiation. DILI seen is mild, transient and may not require treatment interruption. There is good tolerance to HAART and anti-TB with similar immunological outcomes. Genetic make-up mainly CYP2B6 genotype influences the development of efavirenz based HAART liver injury in Tanzanians.

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“…The type and incidence of DILI display wide differences between population and geographical location [14]–[16]. Severe DILI due to HAART is more frequent among Hispanics compared to other populations [14].…”

Section: Introductionmentioning

confidence: 99%

“…Anti-tuberculosis agents are the leading cause for DILI in India, in contrast to acetaminophen in the US and the UK [17]–[19]. The reported incidence of anti-TB therapy and/or HAART associated DILI within Africa varies greatly [10], [15], [16], [20]–[23]. Recent studies indicate association of pharmacogenetic variation with DILI [10], [11], [24]–[26].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Patterns of Liver Toxicity in Patients on Antiretroviral and Anti-Tuberculosis Drugs: A Prospective Four Arm Observational Study in Ethiopian Patients

et al. 2014

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ObjectivesTo evaluate the incidence, type, severity and predictors of antiretroviral and/or anti-tuberculosis drugs induced liver injury (DILI).MethodsA total of 1,060 treatment naive patients were prospectively enrolled into four treatment groups: HIV patients receiving efavirenz based HAART alone (Arm-1); TB-HIV co-infected patients with CD4≤200 cells/μL, receiving concomitant rifampicin based anti-TB and efavirenz based HAART (Arm-2); TB-HIV co-infected patients with CD4>200 cells/μL, receiving anti-TB alone (Arm-3); TB patients taking rifampicin based anti-TB alone (Arm-4). Liver enzyme levels were monitored at baseline, 1st, 2nd, 4th, 8th, 12th and 24th weeks during treatment. CD4 and HIV viral load was measured at baseline, 24th and 48th weeks. Data were analyzed using multivariate Cox Proportional Hazards Model.ResultsA total of 159 patients (15%) developed DILI with severity grades 1, 2, 3 and 4 of 53.5%, 32.7%, 11.3% and 2.5% respectively. The incidence of cholestatic, hepatocellular or mixed pattern was 61%, 15% and 24%, respectively. Incidence of DILI was highest in Arm-2 (24.2%)>Arm-3 (10.8%)>Arm-1 (8.8%)>Arm-4 (2.9%). Concomitant anti-TB-HIV therapy increased the risk of DILI by 10-fold than anti-TB alone (p<0.0001). HIV co-infection increased the risk of anti-TB DILI by 4-fold (p = 0.004). HAART associated DILI was 3-fold higher than anti-TB alone, (p = 0.02). HAART was associated with cholestatic and grade 1 DILI whereas anti-TB therapy was associated with hepatocellular and grade ≥ 2. Treatment type, lower CD4, platelet, hemoglobin, higher serum AST and direct bilirubin levels at baseline were significant DILI predictors. There was no effect of DILI on immunologic recovery or virologic suppression rate of HAART.ConclusionHAART associated DILI is mainly cholestatic and mild whereas hepatocellular or mixed pattern with high severity grade is more common in anti-tuberculosis DILI. TB-HIV co-infection, disease severity and concomitant treatment exacerbates the risk of DILI.

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Antituberculosis drug‐induced hepatotoxicity is uncommon in Tanzanian hospitalized pulmonary TB patients

Cited by 11 publications

References 20 publications

Elevated alanine aminotransferase in antiretroviral‐naïve HIV‐infected African patients: magnitude and risk factors

Elevated alanine aminotransferase in antiretroviral‐naïve HIV‐infected African patients: magnitude and risk factors

Liver Enzyme Abnormalities and Associated Risk Factors in HIV Patients on Efavirenz-Based HAART with or without Tuberculosis Co-Infection in Tanzania

Evaluation of Patterns of Liver Toxicity in Patients on Antiretroviral and Anti-Tuberculosis Drugs: A Prospective Four Arm Observational Study in Ethiopian Patients

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