Novel risk factors and early detection of anti tubercular treatment induced liver injury—Looking beyond American Thoracic Society Guidelines

Latief, Muzamil; Dar, Waseem; Sofi, Najeeb Ullah; Dar, Imtiyaz Ahmad; Kasana, Basharat; Hussain, Mir; Arshad, Faheem; Shah, Bashir Ahmad; Koul, Parvaiz A

doi:10.1016/j.ijtb.2016.11.002

Cited by 11 publications

(18 citation statements)

References 21 publications

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“…In our study, the age difference between the two groups was statistically insignificant (p-value 0.261). No association with gender and DILI was found in our study, though certain studies done in North India have found an association with female gender and DILI (7). Interestingly, the same study found an association with EPTB and DILI, as was the case in our study.…”

Section: Resultssupporting

confidence: 54%

“…Similar results have also been observed in a study done by Tweed et al in England (11). In that study, an increased number of HIV-TB coinfection patients showed elevated liver enzymes, but that result was not statistically significant (7). A study was done in South India, which also failed to find such an association (7).…”

Section: Resultsmentioning

confidence: 82%

“…In that study, an increased number of HIV-TB coinfection patients showed elevated liver enzymes, but that result was not statistically significant (7). A study was done in South India, which also failed to find such an association (7). Sharma et al reported low serum albumin as an independent risk factor for the development of DILI (12).…”

Section: Resultsmentioning

confidence: 87%

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Malnutrition as an important risk factor for drug-induced liver injury in patients on anti-tubercular therapy: an experience from a tertiary care center in South India

Ali

Gupta

Saravu

2020

DD&T

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aspartate transaminase, alanine transaminase, body mass index, tuberculosis, adverse drug reaction, nutrition Drug-induced liver injury (DILI) due to anti-tubercular treatment (ATT) leads to increased morbidity and mortality in patients with tuberculosis (TB). The aim of this study was to find the impact of malnutrition on the development of DILI. This was a prospective cohort study (September 2017 to August 2019) in which all newly diagnosed in-patients with tuberculosis above the age of 18 years were included. Those patients with a body mass index (BMI) of < 18.5 kg/m 2 were considered malnourished. The patients were monitored for the development of DILI. Liver function tests were done at the baseline (before initiation of ATT), on the third day and at discharge in all the patients. Chi-square tests and conditional multiple logistic analysis was performed to identify risk factors associated with DILI. Out of the 319 subjects who were enrolled, a total of 138 patents chose to follow up at our hospital. A total of 14 patients (10%) developed DILI. The median time to onset of DILI was found to be ten days. Extra-pulmonary TB, low BMI and high baseline liver enzyme levels had a significant association with the development of DILI (p < 0.05). Low serum albumin had increased odds ratio but wasn't statistically significant. Malnutrition is an important risk factor for TB-DILI.

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Section: Resultssupporting

confidence: 54%

Section: Resultsmentioning

confidence: 82%

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Malnutrition as an important risk factor for drug-induced liver injury in patients on anti-tubercular therapy: an experience from a tertiary care center in South India

Ali

Gupta

Saravu

2020

DD&T

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“…4 Hepatotoksisitas pada pasien TB paru sebesar 25,7%, pada TB ekstraparu 55,4%, dan 18,9% pada TB milier atau TB diseminata. 5 Kejadian drug induced hepatitis (DIH) pada kasus TB sulit diprediksi, penelitian melaporkan faktor risiko terjadinya DIH selama pemberian OAT yaitu: penyakit hati sebelumnya, khususnya terkait dengan infeksi virus kronis seperti hepatitis B, C, dan HIV, alkoholik, usia lanjut, dan malnutrisi. 6,7 Terdapat pilihan regimen yang beragam dalam reintroduce OAT pada DIH, namun belum ada pedoman konsensus.…”

Section: Pendahuluanunclassified

“…22 Tingkat hepatotoksisitas karena obat dibagi menjadi 4 berdasarkan kriteria WHO, yaitu sebagai berikut: 7 a. Derajat 1 (ringan): peningkatan SGPT < 2,5 kali batas atas normal (51-125 U/L) b. Derajat 2 (ringan): peningkatan SGPT 2,5 sampai 5 kali batas atas normal (126-250 U/L) c. Derajat 3 (sedang): peningkatan SGPT 5 sampai 10 kali batas atas normal (251-500 U/L) d. Derajat 4 (berat): peningkatan SGPT > 10 kali batas atas normal (>500 U/L) Berdasarkan pedoman ATS, beberapa faktor risiko yang diketahui menjadi predisposisi untuk terjadinya DIH akibat OAT yaitu konsumsi etanol yang lama, hepatitis virus, penyakit hati sebelumnya, kehamilan atau 3 bulan post partum, konsumsi obat hepatotoksik, nilai baseline SGOT/SGPT/bilirubin yang abnormal, infeksi HIV, dan usia > 35 tahun. 5,23 Jenis kelamin perempuan dipertimbangkan sebagai faktor predisposisi terjadinya toksisitas OAT, yang khususnya meningkat saat kehamilan. Penjelasan lainnya yaitu adanya peningkatan aktivitas sitokrom P450 3a pada perempuan dan variasi farmakokinetik meliputi pola asetilasi yang lebih lambat dan IMT yang lebih rendah.…”

Section: Kasusunclassified

Drug Induced Hepatitis pada Tuberkulosis Paru dengan Multisite Tuberkulosis Ekstraparu

Wesnawa

Kusmiati

2020

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Background: Tuberculosis (TB) continues to be a major health problem in developing country. Lung is the most common site for Mycobacterium tuberculosis (MTB) infection, but dissemination may occur to any part of the body resulting in extrapulmonary TB. Hepatotoxicity is one of the most frequent adverse events that occur during TB treatment. Case: A 35-year-old female patient came with cough, dyspnea, fever, abdominal pain, history of mass in right inguinal lymph node, and malnutrition. Histopathology from excisional biopsy of inguinal lymph node showed granulomatous inflammation. Computed tomography of abdomen showed intraabdominal TB. Chest X-ray showed right pleural effusion, with exudate pleural fluid and mononuclear dominant. After 1 week consuming antituberculous drug, patient got nausea and vommiting, increased of ALT and AST, total and direct bilirubin. Antituberculous drug was stopped and switched to levofloxacin, ethambutol, and streptomycin. After clinical improvement and liver function return to normal, desensitization of rifampicin and isoniazide was started. Desensitization started with rifampicin for three days, and followed with isoniazide for three days. In total, the patient got rifampicin, isoniazide, and ethambutol for 9 months. Evaluation of treatments are clinical improvement and weight gain. Acid fast baccili sputum was negatif, no pleural effusion on chest X-ray, and normal abdominal ultrasound. Conclusion: MTB can spread to other organs which cause multisite extrapulmonary TB. Side effect can occur during TB treament, and this is not the reason to stop the therapy. Individual ATD therapy shows good response in this case.

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Outcomes and Predictors of Mortality in Patients With Drug-Induced Liver Injury at a Tertiary Hospital in South India: A Single-Centre Experience

Kumar

Remalayam

Varghese

et al. 2021

Journal of Clinical and Experimental Hepatology

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Introduction: Drug-induced liver injury (DILI) is an important cause of acute liver failure with significant morbidity and mortality. The outcome of DILI varies widely according to the drug implicated and the type of liver injury. Owing to the heterogeneous nature of liver injury, knowledge on clinical course and prognosis of DILI is limited. We had undertaken this study to determine the clinical characteristics, outcomes, and predictors of mortality in patients with DILI. Materials and methods: This prospective study was conducted from January 2015 through December 2018. We analyzed the drugs implicated, clinical course, and the outcome. Causality assessment was performed by using Roussel Uclaf Causality Assessment Method scoring. Patients were followed for 6 months until recovery/death or liver transplantation. Results: There were 133 cases with DILI. The mean age was 47.6 years, and 51.9% of them were men. Drugs causing DILI were antitubercular drugs (37.5%) followed by neuropsychiatric drugs (16.5%), antibiotics/antifungals (12%), complementary and alternative medicine (10.5%), immunomodulatory/chemotherapeutic drugs (10.5%), and nonsteroidal antiinflammatory drugs (7.5%). Eighty-two (61.6%) patients were classified as hepatocellular, 30 (22.5%) as mixed and 21 (15.7%) as cholestatic type of injury. There was no significant difference in the mortality and morbidity between the three types of liver injury. There were 18 deaths (13.5%), of which antitubercular drugs constituted the majority (55.5%) followed by neuropsychiatric drugs (27.7%) and complementary and alternative medicine (16.6%). Based on receiver operating characteristic curve analysis, model for end-stage liver disease (MELD) score >28, mean international normalized ratio (INR) >1.97, mean bilirubin level >15.6 mg/dl, and creatinine level >1.35 mg/dl were associated with mortality. Conclusion: Although DILI is uncommon, it has significant morbidity and mortality. Antitubercular drugs were the most common cause for DILI and DILI-related mortality in our study. Variables such as MELD, INR, bilirubin, albumin, and creatinine help in predicting severity of liver injury and may help in triaging the patient for referral for liver transplantation.

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Novel risk factors and early detection of anti tubercular treatment induced liver injury—Looking beyond American Thoracic Society Guidelines

Cited by 11 publications

References 21 publications

Malnutrition as an important risk factor for drug-induced liver injury in patients on anti-tubercular therapy: an experience from a tertiary care center in South India

Malnutrition as an important risk factor for drug-induced liver injury in patients on anti-tubercular therapy: an experience from a tertiary care center in South India

Drug Induced Hepatitis pada Tuberkulosis Paru dengan Multisite Tuberkulosis Ekstraparu

Outcomes and Predictors of Mortality in Patients With Drug-Induced Liver Injury at a Tertiary Hospital in South India: A Single-Centre Experience

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