Antituberculosis drug-induced hepatotoxicity: a comparison between patients with and without human immunodeficiency virus seropositivity

Coca, Natalia Saldanha Magalhães; Oliveira, Marcelo Silva de; Voieta, Izabela; Antunes, Carlos Maurício de Figueiredo; Lambertucci, José Roberto

doi:10.1590/s0037-86822010000600004

Cited by 14 publications

(17 citation statements)

References 29 publications

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“…The prevalence of elevated ALT (13%) found in our study is lower than that reported among pre‐ART HIV‐infected individuals in Europe and North America, where rates vary between 19 and 29%, but similar to the findings of studies from Africa . In a multinational study of HIV‐infected patients in Kenya, Zambia and Thailand, baseline ALT > 40 IU/L was present in about 14% of 812 HIV‐infected patients .…”

Section: Discussionsupporting

confidence: 80%

“…There are several reasons for this difference. First, in the studies from Europe and North/South America, male patients represented between 63 and 94% of the study population, whereas in our study female patients accounted for 71% of the study population . Secondly, an inverse relationship between Black ethnicity and chronic ALT elevation has been reported in several studies of HIV‐infected patients .…”

Section: Discussionmentioning

confidence: 52%

“…Similarly, Coca et al . 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 .…”

Section: Discussionmentioning

confidence: 66%

“…Interestingly, pregnant HIVinfected patients were at a reduced risk for elevated baseline ALT compared with nonpregnant women. There have been contradictory reports demonstrating the risk of elevated liver enzymes among pregnant HIV-infected women exposed to ART, particularly nevirapine [22][23][24]. There are no data, however, to suggest that the same risk applies to pregnant women in the absence of ART [25] and this therefore deserves further study.…”

Section: Discussionmentioning

confidence: 98%

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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: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 98%

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

et al. 2012

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“…The recommended regimen in this population is isoniazid, pyrazinamide and ethambutol with moxifloxacin or levofloxacin [105].…”

Section: Special Situationsmentioning

confidence: 99%

The risk of tuberculosis in transplant candidates and recipients: a TBNET consensus statement

Bumbăcea

Arend

Eyüboğlu³

et al. 2012

Eur Respir J

234

261

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Tuberculosis (TB) is a possible complication of solid organ and hematopoietic stem cell transplantation. The identification of candidates for preventive chemotherapy is an effective intervention to protect transplant recipients with latent infection with Mycobacterium tuberculosis from progressing to active disease. The best available proxy for diagnosing latent infection with M. tuberculosis is the identification of an adaptive immune response by the tuberculin skin test or an interferon-c based ex vivo assay. Risk assessment in transplant recipients for the development of TB depends on, among other factors, the locally expected underlying prevalence of infection with M. tuberculosis in the target population. In areas of high prevalence, preventive chemotherapy for all transplant recipients may be justified without immunodiagnostic testing while in areas of medium and low prevalence, preventive chemotherapy should only be offered to candidates with positive M. tuberculosis-specific immune responses. The diagnosis of TB in transplant recipients can be challenging. Treatment of TB is often difficult due to substantial interactions between anti-TB drugs and immunosuppressive medications. This management guideline summarises current knowledge on the prevention, diagnosis and treatment of TB related to solid organ and hematopoietic stem cell transplantation and provides an expert consensus on questions where scientific evidence is still lacking. KEYWORDS: Guideline, management, Mycobacterium tuberculosis, transplantation, tuberculosis T uberculosis (TB) is caused by the pathogenic species of the Mycobacterium tuberculosis complex. Only a minority of individuals who develop an adaptive immune response following infection with M. tuberculosis will ever develop TB, with the actual risk depending on the extent to which the host immune system provides a successful or inadequate response [1,2]. Therefore, individuals with impaired immune response, such as solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients, are more prone to develop TB than immunocompetent persons. TB in transplant recipients is more frequent compared to the general population (estimates from the last decades state 20-74 times as frequent in SOT [3,4] and twice as frequent in HSCT [5]), and more often fatal (up to 31% in SOT [6] and up to 50% in HSCT recipients [7]), thus adding effectiveness to interventions for its prevention, even in the face of difficulties, with treatment related to adverse drug events and drug-drug interactions. Active TB in transplant recipients can result from latent infection with M. tuberculosis (LTBI) in the transplant candidate or in the donor tissue, or from de novo post-transplant infection. These various scenarios prompt for targeted pre-transplant screening of both recipient and, if possible, donors to allow focused management of recipients selected for preventive intervention in the pre-and/or posttransplant period. The term ''preventive chemotherapy'' is used to denote treatmen...

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Hepatocyte growth factor enhances the clearance of a multidrug‐resistant Mycobacterium tuberculosis strain by high doses of conventional chemotherapy, preserving liver function

Bello-Monroy

Mata-Espinosa

Enríquez-Cortina

et al. 2019

Journal Cellular Physiology

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Tuberculosis (TB) is one of the deadliest infectious diseases in humankind history.Although, drug sensible TB is slowly decreasing, at present the rise of TB cases produced by multidrug-resistant (MDR) and extensively drug-resistant strains is a big challenge. Thus, looking for new therapeutic options against these MDR strains is mandatory. In the present work, we studied, in BALB/c mice infected with MDR strain, the therapeutic effect of supra-pharmacological doses of the conventional primary antibiotics rifampicin and isoniazid (administrated by gavage or intratracheal routes), in combination with recombinant human hepatocyte growth factor (HGF).This high dose of antibiotics administered for 3 months, overcome the resistant threshold of the MDR strain producing a significant reduction of pulmonary bacillary loads but induced liver damage, which was totally prevented by the administration of HGF. To address the long-term efficiency of this combined treatment, groups of animals after 1 month of treatment termination were immunosuppressed by glucocorticoid administration and, after 1 month, mice were euthanized, and the bacillary load was determined in lungs. In comparison with animals treated only with a high dose of antibiotics, animals that received the combined treatment showed significantly lower bacterial burdens. Thus, treatment of MDR-TB with very high doses of primary antibiotics particularly administrated by aerial route can produce a very good therapeutic effect, and its hepatic toxicity can be prevented by the administration of HGF, becoming in a new treatment modality for MDR-TB. K E Y W O R D SHGF, isoniazid, rifampicin, liver, tuberculosis

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Antituberculosis drug-induced hepatotoxicity: a comparison between patients with and without human immunodeficiency virus seropositivity

Cited by 14 publications

References 29 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

The risk of tuberculosis in transplant candidates and recipients: a TBNET consensus statement

Hepatocyte growth factor enhances the clearance of a multidrug‐resistant Mycobacterium tuberculosis strain by high doses of conventional chemotherapy, preserving liver function

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