THE RISK FACTORS FOR DRUG INDUCED HEPATITIS IN PULMONARY TUBERCULOSIS PATIENTS IN DR. SOETOMO HOSPITAL
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Tuberculosis (TB) is still a major public health problem in Indonesia. Anti-tuberculosis drug-induced hepatotoxicity (DIH) is common side effect leading to changes in treatment regimens, and the less effective second-line treatments. Several risk factors such as age, sex, body mass index (BMI) and acetylization status for hepatotoxicity were suggested in previous studies but in the fact, those are often not related to DIH incidence after receiving standard TB treatment regimen. The aim of this study was to asses the role of risk factors in the DIH incidence in pulmonary TB patients receiving standard TB treatment regimen in Dr. Soetomo Hospital, Surabaya. Study design was analytic observational with case control. The subjects were 30 TB DIH patients and 31 TB non-DIH patients receiving standard national TB program therapy. DIH severity was divided based on International DIH Expert Working Group. Demographic data and BMI status were taken from medical records. The age classification are ≥35 years old and <35 years old as one of the risk factors studied. DNA sequencing was used to assess single-nucleotide polymorphisms in NAT2 coding region to evaluate acetylator status from blood samples. The risk factors were evaluated using chi-square test and Mantel-Haenszel test. Significant association between low BMI and DIH in general was identified (OR=3.017; 95% CI=1.029-8.845) and more significant association between low BMI and moderate DIH (OR=15.833; 95% CI=1.792-139.922). Age, sex, and acetylization status has no significant correlation with DIH incidence in general. Significant association between slow acetylator phenotype and incidence of moderate DIH was identified (OR=7.125; 95% CI= 1.309-38.711). In conclusion, some risk factors were correlated to DIH incidence in pulmonary TB patients
receiving standart TB treatment regimen.
REFERENCES
Aithal GP, Watkins PB, Andrade RJ, Larrey D, Molokhia M, Takikawa H, et al. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther. 2011 Jun; 89(6):806–15.
Tostmann A, Boeree MJ, Aarnoutse RE, de Lange WCM, van der Ven AJAM, Dekhuijzen R. Antituberculosis drug-induced hepatotoxicity: concise up-to-date review. J Gastroenterol Hepatol. 2008 Feb; 23(2):192–202.
Gaude GS, Chaudhury A, Hattiholi J. Drug-induced hepatitis and the risk factors for liver injury in pulmonary tuberculosis patients. J Fam Med Prim care. 4(2):238–43.
Singla R, Sharma SK, Mohan A, Makharia G, Sreenivas V, Jha B, et al. Evaluation of risk factors for antituberculosis treatment induced hepatotoxicity. Indian J Med Res. 2010 Jul;132:81–6.
Naqvi IH, Mahmood K, Talib A, Mahmood A. Antituberculosis Drug-Induced Liver Injury: An Ignored Fact, Assessment of Frequency, Patterns, Severity and Risk Factors. Open J Gastroenterol. 2015;5(12):173–84.
Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, et al. Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology. 2008 Dec;135(6):1924–34, 1934-4.
An H, Wu X, Wang Z, Xu J, Zheng S, Wang K. The clinical characteristics of anti-tuberculosis drug induced liver injury in 2457 hospitalized patients with tuberculosis in China. African J Pharm Pharmacol. 2013;7(13):710–4.
Lucena MI, Andrade RJ, Kaplowitz N, García-Cortes M, Fernández MC, Romero-Gomez M, et al. Phenotypic characterization of idiosyncratic drug-induced liver injury: the influence of age and sex. Hepatology. 2009 Jun;49(6):2001–9.
Makhlouf HA, Helmy A, Fawzy E, El-Attar M, Rashed HAG. A prospective study of antituberculous drug-induced hepatotoxicity in an area endemic for liver diseases. Hepatol Int. 2008 Sep; 2(3):353–60.
Mohan N, Kumar J, Chakrawarty A, Ranjan P. Comprehensive review of anti-tubercular treatment induced liver injury. Int J Basic Clin Pharmacol. 2015;397–403.
Sistanizad M, Azizi E, Khalili H, Hajiabdolbaghi M, Gholami K, Mahjub R. Antituberculosis Drug-Induced Hepatotoxicity in IranianTuberculosis Patients: Role of Isoniazid Metabolic Polymorphism. Iran J Pharm Res IJPR. 2011;10(3):633–9.
Saha A, Shanthi F X M, Winston A B, Das S, Kumar A, Michael JS, et al. Prevalence of Hepatotoxicity From Antituberculosis Therapy: A Five-Year Experience From South India. J Prim Care Community Health. 2016;7(3):171–4.
Chang KC, Leung CC, Yew WW, Lau TY, Tam CM. Hepatotoxicity of pyrazinamide: cohort and case-control analyses. Am J Respir Crit Care Med. 2008 Jun 15;177(12):1391–6.
NATs: Human NA. Greece: Department of Molecular Biology and Genetics Democritus University of Thrace. Database of Arylamine N-acetyltransferases (NATs): Human NAT2 Alleles [online].; 2013.
Khan N, Pande V, Das A. NAT2 sequence polymorphisms and acetylation profiles in Indians. Pharmacogenomics. 2013;14(3):289–303.
Devarbhavi H, Dierkhising R, Kremers WK, Sandeep MS, Karanth D, Adarsh CK. Single-center experience with drug-induced liver injury from India: causes, outcome, prognosis, and predictors of mortality. Am J Gastroenterol. 2010 Nov;105(11):2396–404.
Wondwossen Abera, Waqtola Cheneke, Gemeda Abebe. Incidence of antituberculosis-drug-induced hepatotoxicity and associated risk factors among tuberculosis patients in Dawro Zone, South Ethiopia: A cohort study. Int J mycobacteriology. 2016 Mar;5(1):14–20.
Devarbhavi H. An Update on Drug-induced Liver Injury. J Clin Exp Hepatol. 2012 Sep;2(3):247–59.
Kumar R, Shalimar, Bhatia V, Khanal S, Sreenivas V, Gupta SD, et al. Antituberculosis therapy-induced acute liver failure: magnitude, profile, prognosis, and predictors of outcome. Hepatology. 2010 May;51(5):1665–74.
Kementrian Kesehatan Republik Indonesia. The Joint External TB Monitoring Mission (JEMM TB). 2010;71–5.
Ramappa V, Aithal GP. Hepatotoxicity Related to Anti tuberculosis Drugs: Mechanisms and Management. J Clin Exp Hepatol. 2013 Mar;3(1):37–49.
Mitchell SJ, Hilmer SN. Drug-induced liver injury in older adults. Ther Adv drug Saf. 2010 Dec;1(2):65–77.
Thorn CF, Aklillu E, McDonagh EM, Klein TE, Altman RB. PharmGKB summary: caffeine pathway. Pharmacogenet Genomics. 2012 May;22(5):389–95.
Yuliwulandari R, Susilowati RW, Wicaksono BD, Viyati K, Prayuni K, Razari I, et al. NAT2 variants are associated with drug-induced liver injury caused by anti-tuberculosis drugs in Indonesian patients with tuberculosis. J Hum Genet. 2016 Jun;61(6):533–7.
Teixeira RLDF, Morato RG, Cabello PH, Muniz LMK, Moreira A da SR, Kritski AL, et al. Genetic polymorphisms of NAT2, CYP2E1 and GST enzymes and the occurrence of antituberculosis druginduced hepatitis in Brazilian TB patients. Mem Inst Oswaldo Cruz. 2011;106(6):716–24.
Satyaraddi A, Velpandian T, Sharma SK, Vishnubhatla S, Sharma A, Sirohiwal A, et al. Correlation of plasma anti-tuberculosis drug levels with subsequent development of hepatotoxicity. Int J Tuberc Lung Dis. 2014 Feb;18(2):188–95, i–iii.
Jeong I, Park J-S, Cho Y-J, Yoon H Il, Song J, Lee C-T, et al. Druginduced hepatotoxicity of anti-tuberculosis drugs and their serum levels. J Korean Med Sci. 2015 Feb;30(2):167–72.
Lv X, Tang S, Xia Y, Zhang Y, Wu S, Yang Z, et al. NAT2 genetic polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in Chinese community population. Ann Hepatol. 11(5):700–7.
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