Monitoring and management of antituberculosis drug induced hepatotoxicity

Agal, Subhash; Baijal, Rajiv; Pramanik, Snehanshu; Patel, Nikhil; Gupte, Parijat; Kamani, Praful; Amarapurkar, Deepak

doi:10.1111/j.1440-1746.2005.04048.x

Cited by 69 publications

(56 citation statements)

References 26 publications

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“…Five patients (13.2%) with anti-TB DIH death during TB treatment, one of them was diagnosed acute liver failure due to anti-TB DIH. The mortality rate in this study was similar to the study that conducted by Agal et al with mortality rate of 16.6% [20]. The other prospective study showed that none of TB patients with DIH was death from group TB patient that performed routine monitoring liver function.…”

Section: Discussionsupporting

confidence: 89%

The Impact of Antituberculosis Drug-Induced Hepatotoxicity to Succesful Tuberculosis Treatment in Indonesia

Maria

Radji

Burhan

2017

Asian J Pharm Clin Res

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Objective: This study aimed to evaluate the impact of antituberculosis (anti-TB) drug-induced hepatotoxicity (DIH) to outcome TB treatment.Methods: A cohort retrospective study conducted at a tertiary hospital in Jakarta -Indonesia, from the period of 2013-2016. A total of 76 samples of TB patient with and without anti-TB DIH were analyzed.Results: Successful outcome TB treatment for TB patient with anti-TB DIH is 47.4% compared to TB patient without anti-TB DIH is 78.9%. Relative risk (RR) analysis showed that risk of unsuccessful TB treatment for TB patient with anti-TB DIH is 2.50 fold higher (95% confidence interval: 1.259-4.960) than TB patient without anti-TB DIH. Age, sex, and comorbidities are not statistically significant to outcome TB treatment. For TB patient with anti-TB DIH, onset anti-TB DIH and recurrence anti-TB DIH also not statistically significantly influence outcome TB. The mean duration of treatment for a successful outcome for TB patient with and without anti-TB DIH was statistically significant (p<0.05), respectively, 8.44±1.85 and 6.52±0.93 months. Conclusion:Anti-TB DIH increases the risk of unsuccessful and prolonged duration TB treatment.

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Section: Discussionsupporting

confidence: 89%

The Impact of Antituberculosis Drug-Induced Hepatotoxicity to Succesful Tuberculosis Treatment in Indonesia

Maria

Radji

Burhan

2017

Asian J Pharm Clin Res

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“…Early identification may offer scope for applying interventions to improve prognosis. Other studies have confirmed such benefit of regular monitoring [46,47] . Rapid increase of ALT implies need to investigate viral hepatitis and toxicity to any other drugs and more frequent monitoring, e.g.…”

Section: Conclusion and Epiloguementioning

confidence: 62%

Liver Dysfunction in Pulmonary Tuberculosis Patients on DOTS: A Study and Review

Pandit

Pandey

2016

Journal of Gastroenterology and Hepatology Research

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eGFR were done. Development of hepatotoxicity was watched by monthly monitoring of liver enzymes and bilirubin serum profiles. RESULT: The selected 148 patients were older and four fifths were males. 16 patients developed ATT-DIH at first or second month monitoring following DOTS. They were more undernourished, hypoproteinaemic, bore more extensive disease and were sputum AFB positive. Their eGFR profiles were normal but significantly lower and plasma antioxidant capacity significantly reduced. Oxidative stress marker levels also were insignificantly raised. They exhibited subclinical elevation of serum enzymes AST and ALT. No significant influence of age and gender was seen on incidence of ATT-DIH. CONCLUSION: Frailty with extensive disease constituted phenotype vulnerable to ATT-DIH. Hypoalbuminaemia, reduced plasma antioxidant capacity, subclinical elevated profile of transaminases before starting DOTS were forewarning laboratory indices. LFT ought to be monitored at fortnight, a month and at 2 months in such patients as minimum necessity to timely detect and address hepatotoxicity. INTRODUCTIONTuberculosis continues as huge health care problem globally. Currently recommended first line treatment for TB includes regimen of isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA) and ethambutol (EMB) for initial 2 months followed by 4 months of INH and RMP and/or EMB [1] . Among the first line quadruple therapy drugs (INH, RMP, PZA, EMB), first three are metabolized mainly by the liver and are potentially hepatotoxic. A fair fraction of TB patients on chemotherapy with isoniazide and rifampicin exhibit elevations in serum levels of liver enzymes, alanine aminotransferase (ALT, earlier called SGPT) and aspartate aminotransferase (AST, earlier SGOT) activities. A small fraction of these can worsen further to compel ABSTRACT CONTEXT: Phenomenal number of people suffers tuberculosis and is prescribed primary line DOTS antitubercular chemotherapy. Evidence based clinical practice to minimize risk of hepatotoxicity is primary imperative. AIM: Study generates evidence for predicting individual hepatotoxic risk using patient's constitutional and health parameters and disease characteristics and adopting right course of management. It is observational study in patients consecutively selected by defined inclusion and exclusion criteria. METHODS: Newly enrolled pulmonary tuberculosis patients for DOTS were studied to examine host and disease specific predictors of hepatotoxicity risk. Pretreatment baseline liver function tests and

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“…The frequency of hepatotoxicity varies from 2 to 28% in different populations and occurs even when the drug has been given at the recommended doses (Tostmann et al, 2008). Approximately 9.5% of Indian patients have been reported to develop antitubercular therapy (ATT)-induced hepatotoxicity (Agal et al, 2005). This often results in discontinuation of the most effective first-line drugs.…”

Section: Introductionmentioning

confidence: 99%

“…Non-compliance not only leads to morbidity and mortality but also results in the emergence of drug-resistant strains. Majority of ATT-induced hepatotoxicity incidences are evident in the first month of treatment for a combination of RIF and INH but can occur up to the third month when PYZ is combined (Agal et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Studies on toxicity of antitubercular drugs namely isoniazid, rifampicin, and pyrazinamide in an in vitro model of HepG2 cell line

et al. 2010

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Antitubercular drugs (ATT) are known to be majorly metabolized and detoxified in liver by both Phase I and Phase II group of drug metabolizing enzymes. These drugs as well as their metabolites are toxic and during this process cause injury to liver. In this study, we have investigated the in vitro hepatotoxic potential of both individual as well as combination ATT drugs using an in vitro model of human hepatocellular carcinoma cell line (HepG2). The cells were treated with varied concentrations of ATT drugs namely isoniazid (INH), rifampicin (RIF), and pyrazinamide (PYZ) for different durations. Cytotoxicity assay using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide) as well as morphological analysis using phase contrast microscopy have shown that concentrations used were not cytotoxic. However, pretreatment with sub-cytotoxic concentrations of INH and PYZ increased the toxicity with the same drugs. This report corroborates the clinical finding that long-term treatment as well combination drug therapy with ATT induces hepatotoxicity rather than individual drugs.

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Monitoring and management of antituberculosis drug induced hepatotoxicity

Abstract: Periodic laboratory monitoring is important in detecting hepatotoxicity at an early stage, thereby preventing mortality. Sequential reintroduction is often successful.

Cited by 69 publications

References 26 publications

The Impact of Antituberculosis Drug-Induced Hepatotoxicity to Succesful Tuberculosis Treatment in Indonesia

The Impact of Antituberculosis Drug-Induced Hepatotoxicity to Succesful Tuberculosis Treatment in Indonesia

Liver Dysfunction in Pulmonary Tuberculosis Patients on DOTS: A Study and Review

Studies on toxicity of antitubercular drugs namely isoniazid, rifampicin, and pyrazinamide in an in vitro model of HepG2 cell line

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