DOI: http://dx.doi.org/10.18203/2349-3933.ijam20161485

Incidence of hepatotoxicity in directly observed treatment short course

Abhishek Chandra, Shivani Swami, . Girijanair

Abstract


Background: Antitubercular treatment induced hepatotoxicity usually has benign course, but may result in serious morbidity and even mortality. This study was undertaken to determine the incidence of hepatotoxicity in intermitted regimens directly observed treatment, short course (DOTS) and to evaluate the risk factors such as age, sex, nutritional status, disease extent, in the development of antitubercular drug induced hepatotoxicity in intermitted regimens (DOTS).

Methods: This was an observational study. All adults and adolescents above 15 years of age and weight more than 30 kilogramss, of either sex, on antitubercular treatment under intermitted regimens (DOTS), coming to chest and tuberculosis. Out-patient department of Dr. D.Y. Patil, hospital and research centre, Navi Mumbai, India, were included. Statistical analysis based on t- test done, predictability calculated to know the significance of study.

Results: 50 patients at random on intermitted regimens (DOTS) of antitubercular treatment. Majority (52%) were aged between 15-30 years. There were 24 (48%) males and 26 (52%) females. Serum bilirubin show a rise mean values between 2nd week (SD±053) p-value<0001(significant). Serum glutamic-pyruvic transaminase (SGPT) values show a rise in mean values between 2nd week (SD ±17.56) 4th week (SD±35.37) followed by fall in 6th week, p-value<001(significant), Serum glutamic-oxaloacetic transaminase (SGOT) value show a rise in mean values between 2nd week (SD±14.85) and 6th week (SD±26.18) followed by fall in 8th week, p-value<0001(significant). Mean serum albumin values show a rise in 2nd week (SD±0.53) and fall in the 4th week (SD±0.56) followed by a rise at 6th and 8th week, p-value<0001 (significant). Mean total protein value showed a fall from 2nd week (SD±1.16) to 8th week (SD±0.93) p-value<0001(significant).

Conclusions: Patients on antitubercular regimen should be educated about symptomatology related to hepatotoxicity, and they should be advised to consult the physician if symptoms occur. This will ensure reduction in dependency on repeated biochemical examination and also reduce patient’s suffering.


Keywords


Antitubercular regimen, Hepatotoxicity

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References


Mahashur AA, Prabhudesai PP. Hepatitis and antitubercular therapy. J Asso Physicians India. 1991;39:595-6.

Gangadharam TS, PR. Isoniazid, rifampicin and hepatotoxicity (editorial). Am Rev Respir Dis. 1986;133:963-5.

Moulding TS, Radeker AG, Kanel GC. Twenty isoniazid associated death in one state. Am Rev Respir Dis. 1989;140:700-5.

Control. Who report 2001. Geneva, Switzerland:WHO/CDS/TB;2001.287

Parthasarathy R, Sarma GR, Janardhanam B, Ramachandran P, Santha T, Shivasubramanian S, et al. Hepatic toxicity in south Indian patients during treatment of tuberculosis with short-course regimens containing isoniazid, rifampicin and pyrazinamide. Tubercle. 1986;67:99-108.

Purohit SD, Gupta PR, Sharma TN, Gupta DN, Chawla MP, Rifampician and hepatic toxicity. Indian J Tuberc. 1983;30:107-9.

Taneja DP, Kaur D. Study on hepatotoxicity and other side effects of antitubercular drugs. J indian Med Assoc. 1990;88:278-80.

Mehta S. Malnutrition and drug: clinical implications. Dev. Pharmacol Ther. 1990;15:159-65.

Snider DE, Long MW, Cross FS, Farer LS. Six months isoniazid and rifampician therapy for pulmonary tuberculosis: report of a United States public health services co-operative trial. Am Rev Respir Dis. 1984;129:573-9.

Dutt AK, Moers D, Stead WW. Short course chemotherapy for tuberculosis with mainly twice-twice isoniazid and rifampicin: community physicians seven-year experience with mainly outpatients. Am J med. 1984;77:233-42.

British thoracic and tuberculosis Association. Short course chemotherapy in pulmonary tuberculosis. Lancet. 1975;305(7899):119-24.

Steele MA, Burk RF, Desprez RM. Hepatitis with isoniazid and rifampician: a meta- analysis. Chest. 1991;99:465-71.

Centers for disease control. National consensus conferences on tuberculosis, preventive treatment of tuberculosis. Chest. 1985;87:128-32.

Gronhagen RC, Hellstrom PE, Froseth B. Predisposing factors in hepatitis induced by isoniazid rifampician treatment of tuberculosis. Am Rev Respir Dis. 1978;118:161-6.

Rugmini PS, Mehta S. Hepatotoxicity of isoniazid and rifampician in children. Indian J Pediatr. 1981;21:119-24.

Riska N. Hepatitis cases in isoniazid treated groups and in a control group. Bull Int Union Tuberc. 1976;51:203-6.

Wu JC, Lee SD, Yeh PF. Isoniazid, rifampicin induced hepatitis in hepatitis B carriers. Gastroenterology. 1990;98:502-4.

Kumar A, Mishra PK, Mehrotra R, Govil YC, Rana GS. Hepatotoxicity of rifampicin and isoniazid: is it all drug induced hepatitis? Am Rev Respir Dis. 1991;143:1350-2.

Pande JN, Singh SPN, Khilnani GC, Khilnani S, Tandon RK. Risk factors for hepatotoxicity from antitubercular drugs: a case- control study. Thorax. 1996;51:132-6.

Gurumurthy P, Krishnamurthy MS, Nazareth O, Parthasarathy R, Sarma GR, Somasundaram PR. Et al. Lack of relationship between hepatictoxicity and acetylat or phenotypes in 3000 south Indian patients during treatment with isoniazid for tuberculosis. Am Rev Respir Dis. 1984;129:58-61.

Mitchell JR, Thorgiersson UP, Black M. Increased incidence of isoniazid hepatitis in rapid acetylators: possible relation to hydrazine metabolites. Clin Pharmacol Ther. 1975;18:7-19.

Leff DR, Leff AP. TB control policies in major metropolitan health departments in the US. Am J respire Crit Care Med. 1997;156:1487-9.

Cohn HD. Clinical studies with a new rifamycin derivative. J Clin Pharm. 1969;9:118-25.

Capelle P, Dhumeaux D, Mora M, Feldmann C, Berthelot P. Effect of rifampicin on liver function in man. Gut. 1972;13:366-71.

Dhindra VK, Rajpal S, Agarwal N, Agarwal JK, Khan S, Jain SK. Adverse drug reaction observed during DOTS. J Commun Dis. 2004;36(4):251.

Hong Kong chest service/British medical research council. First report: controlled trial of four thrice weekly regimens and a daily regimen all given for 6 months for pulmonary tuberculosis. Lancet. 1981;1:171-4.

Ungo JR, Jones D, Askin D. Anti TB drugs-related hepatotoxicity; the role of hepatitis C and the human deficiency virus. Am J Respir Crit Care Med. 1998;157:1871-6.

Stead WW, To T, Harrison RW. Benefits-risk consideration in preventive treatment for TB in elderly patients. Anal Intern Med. 1987;107:843-5.

Mitchell, Williams R. Liver Transplant for antitubercular drug induced acute liver failure. Lancet. 1995;345:555.

Tuberculosis and Chet Service Centre for health Protection, Department of Health, Hong Kong. Available at, http://www.info.gov.hk/tb_chest/eindex.htm. Accessed on 05 April, 2016.

Mahmood K, Hussain A, Jairamani KL, Talib A, Abbasi B, Salkeen S. Hepatotoxicity with antituberculosis drugs: the risk factors. Pak J Med Sci. 2007;23(1):33-8.

Shakya R, Rao BS, Shrestha B. Management of antitubercular drugs-induced hepatotoxicity and therapy reintroduction strategy in a TB clinic of Nepal. Kathmandu Univ Med J. 2005;3(1):45-9.

Mehta S, Nain CK, Sharma B, Mathur VS. Metabolism of sulphadiazine in children with protein-calorie malnutrition. Pharmacology. 1980;21:369-74.

Sharma SK, Mohan A. Antituberculosis treatment-induced hepatotoxicity: from bench to bedside. In: Gupta SB. Medicine update. 15th edition. India; 2005:479-84.

Anand AV, Seth AK, Paul M, Puri P. Risk Factor of hepatotoxicity during antitubercular treatment 2000-2002. Med J Armed Force Ind. 2006;62:45-9.

Burman WJ, Reves RR. Hepatotoxicity from rifampicin plus pyrazinamide. Am J Rspir Crit Care Med. 2001;164(7):1112-3.

Jong E, Conradie F, Berhanu R, Black A, John MA, Meintjes G, et al. A consensus statement of the tuberculosis control coordinating committee of the Hong Kong department of health and the tuberculosis subcommittee of the coordinating committee in internal medicine of the hospital authority. S Afr J HIV Med. 2013;14(3):113-9.

Dhindra VK, Rajpal S, Agarwal Nishi, Agarwal JK, Khan Shadab, Jain SK. Adverse drug reaction observed during DOTS. J Commun Dis. 2004;36(4):251.

Hong Kong chest service/British medical research council. First report: controlled trial of four thrice weekly regimens and a daily regimen all given for 6 months for pulmonary tuberculosis. Lancet. 1981;1:171-4.

American Thoracic Society Update. Fatal and severe liver injuries associated with rifampicin and pyrazinamide for talent tuberculosis infections, and revisions in American Thoracic Society/CDC recommendations-United States, 2001. Am J Respir Crit Care Med. 2001;164:1319-20.