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Table of Content - Volume 3 Issue 1 - July 2016


 

A study of the various factors associated with drug induced hepatitis in the patients taking antitubercular drugs at tertiary health care centre

 

Abhijit Sayamber

 

Assistant Professor, Department of Pulmonary Medicine, P. D. V. V. P. F. S. Medical College, Ahmednagar, Maharashtra, INDIA.

Email: abhijit.sayamber@gmail.com

 

Abstract              Background: Antituberculous therapy induced hepatitis is an important cause of morbidity and mortality in developing countries where the incidence of pulmonary tuberculosis is high. Aims and Objectives: To study the various factors associated with Drug induced Hepatitis in the patients taking Antitubercular drugs at tertiary health care centre. Methodology: Patient attending OPD at a tertiary hospital who are started on AKT and following regularly will be included. Patient from CAT 1 and from CAT 2 attending OPD who are started on AKT was included (pulmonary and extra pulmonary and CAT1 and CAT 2) During one year June 2009 to May 2010. The qualitative variables was analysed by chi- square test. for the comparison of quantitative data, the students t test was applied. The values of p<0.05 were regarded as significant. Result: The Category of DOTS Treatment, BMI, Sex, Alcohol Intake etc. were not significantly associated with the development of Hepatitis (P>0.05). Conclusion: It can be concluded from our study that Correlation between age, sex and incidence of ATT induced hepatitis is controversial and requires further studies. In our study occurrence was more in young males. Correlation between incidence of ATT induced hepatitis and nutrition is controversial and it is more common in people with low BMI in our study. Chronic alcoholism is not an independent risk factor. However history of prior alcohol induced hepatitis or alcohol induced liver disease has been well established as risk factor for drug induced hepatitis.

Key Words: Drug induced Hepatitis, Antitubercular drugs, Risk factors of Drug induced Hepatitis.

 

INTRODUCTION

Antituberculous therapy induced hepatitis is an important cause of morbidity and mortality in developing countries where the incidence of pulmonary tuberculosis is high. The incidence of pulmonary tuberculosis is high in developing countries1,2. The incidence for tuberculosis in India is 1.68/1000 population3,4. For treatment of pulmonary tuberculosis, multidrug therapy is used worldwide so as to prevent development of drug resistance. The drugs used as first line multidrug therapy are:

  1. Isoniazid
  2. Rifampicin,
  3. Pyrazinamide
  4. Ethambutol.
  5. Streptomycin.

However rifampicin, isoniazid and pyrazinamide all are hepatotoxic5. Despite the avalability of effective chemotherapeutic agents that exist to treat this illness, hepatotoxicity from first line drugs such as isoniazid (INH), rifampicin and pyrazinamide is common and may limit their use6. Several studies has shown that alcohol use6,7,8 increasing age9,10,11,12, nutritional status13,14, presence of chronic liver disease11,12,13 and infection by hepatitis b virus20, infection by hepatitis c virus15,16, certain genetic factors10,11,12 concomitant use of other hepatotoxic drugs14 have been reported to increase the risk of antituberculosis drug induced hepatotoxicity13,14. The exact mechanism of this liver toxicity remains unclear. Populations such as those with human immunodeficiency virus (infection), the elderly, substance abusers and immigrants from countries with a high incidence of TB are more likely to develop DIH17. However results have been reported by other workers and consensus regarding their role is lacking18,19. Role of genetic factors has been suggested by some workers20. There are no definite recommendation as to wether AKT should be stopped (all drugs) and what should be the schedule for reintroduction of these agents21. In view of above the present study is undertaken to study the incidence of AKT induced hepatitis and role of clinical markers in development of AKT induced hepatitis.

 

MATERIAL AND METHODS

Patient ATTending OPD at a tertiary hospital who are started on AKT and following regularly will be included. Patient from CAT 1 and from CAT 2 ATTending OPD who are started on AKT was included (pulmonary and extra pulmonary and CAT1 and CAT 2) During one year June 2009 to May 2010These patients will be started on ATT at DOTS center and will be followed up regularly while they were receiving ATT. The age, sex body mass index and chronic alcoholism affect the development of ATT induced hepatotoxicity and the factors predisposing were studied. The qualitative variables was analysed by chi- square test. for the comparison of quantitative data, the students t test was applied. The values of p<0.05 were regarded as significant. The results are expressed as the mean plus minus SD

 

RESULT                                                   

 

Table 1: Category wise Distribution Of Hepatitis In The Study Group

 

 

 

Presence of hepatitis

Total

Hepatitis

No hepatitis

category

CAT I

Count

3

37

40

% of Total

4.3%

52.9%

57.1%

CAT II

Count

2

28

30

% of Total

2.9%

40.0%

42.9%

Total

Count

5

65

70

% of Total

7.1%

92.9%

100.0%

Applying chi square test p value is o.893 which is not statistically significant

Table 2: Correlation of BMII and hepatitis

 

 

 

Presence of hepatitis

Total

No hepatitis

Hepatitis

BMIcat

<=18.5

Count

28

3

31

% of Total

40.0%

4.3%

44.3%

>18.5

Count

37

2

39

% of Total

52.9%

2.9%

55.7%

Total

 

Count

65

5

70

% of Total

92.9%

7.1%

100.0%

By Application of Chi Square Test P Value Is 0.649 Which Is Not Statistically Significant

 

Table 3: Correlation of sex and hepatitis

 

 

 

Presence of hepatitis

Total

Hepatitis

No hepatitis

Sex

Male

Count

4

43

47

% of Total

5.7%

61.4%

67.1%

Female

Count

1

22

23

% of Total

1.4%

31.4%

32.9%

Total

 

Count

5

65

70

% of Total

7.1%

92.9%

100.0%

By Applying Chi Square Test, P Value Is 1 Which Is Not Statistically Significant

 

Table 4: Correlation of Alcohol Intake and Hepatitis

 

 

 

Presence of hepatitis

Total

No hepatitis

Hepatitis

Alcohol

A

Count

11

1

12

% of Total

15.7%

1.4%

17.1%

NA

Count

54

4

58

% of Total

77.1%

5.7%

82.9%

Total

 

Count

65

5

70

% of Total

92.9%

7.1%

100.0%

By Application of Chi Square Test P Value Is 1 Which Is Not Statistically Significant

 

DISCUSSION

Even though studies have reported that the risk of ATT induced hepatitis increases with advancing age16, 17 done by telemanm. d, cheec.b, earnest. c.r, selft.h. et al. the highest incidence being in individuals greater than 50 years of age. Our study shows the incidence of hepatitis is more in younger age group this is in accordance with nepal study done by rajanishakyarao and bs bhavana shriestha. Similar result was shown by some indian studies. where asno significant correlation was found in afmc study done by scientists as above and two other studies from Spain done by fernandezvillar, r.vazquez, gallado, f.ulloa, v.leiro, m.mosteiro, l.pifieirothus the role for older. Age on incidence of ATT induced hepatitis remains controversial. Also the population studied in this study is of younger age group predominantly also the incidence of tuberculosis is more in younger age group. Females are considered as having higher risk and it was linked to various causes such as lower biotransformation and subsequent clearance of exogenous molecules due to lower level of microsomal enzymes, slow acetylator enzymatic pATTern. However as per popular belief that females are at more risk of developing ATT induced hepatitis. And also studies showing more incidence in female sex.25 This studies were done by kopanoffd. e, snderd, caras g.et al our study showed no significant correlation between female sex and incidence of hepatitis. similar has been reported by previous three studies18 out of the 69 patients who developed hepatotoxicity in nepal study 47 were males aims study also showed more males affected that is 33 out of 60 patients done by Tanejad. P, Kaurd, desprezr. m et al. Also the number of females in the study group was small. Under nutrition has been considered as a risk factor for development of ATT induced hepatitis in the literature and shown to affect the incidence of ATT induced hepatitis. The depletion of glutathione store and slow rate of liver enzyme metabolism was considered responsible. The same is shown by various studies 22 done by gronhagen-riska, C., P. E. hellstrom, and B. Froseth. Indicators were used to assess undernutrition such as BMI, serum albumin level, serum cholesterol level. we used BMI as indicator of under nutrition. In our study incidence of hepatitis was more in patients with low BM. Chronic alcoholism causes liver damage, hepatitis and cirrhosis this is thought to increase the risk of hepatitis in patients on ATT. chronic alcoholism has been stated as important risk factor for hepatitis and studies also shows same results. However in our study we did not find significant correlation between chronic alcoholism and ATT induced hepatitis. This is in accordance to results found by 3 studies previously done 23 because they did not have alcohol induced liver disease. Scientists name as mentioned above. also all the 5 patients who developed hepatitis were not having previous history of hepatitis in our study. We also assessed time of development of hepatitis in patients out of 5 patients who developed hepatitis in our study, two developed within fifteen days and three developed within second month this was in accordance to the results obtained in various studies done previously stating that hepatitis is common in first 8 weeks of therapy. This also supports the possibility of immunological mechanism for in induced hepatotoxicity. Patients enrolled in this study were taking combination of drugs. Due to this reason it is difficult to conclude which drug was the main culprit for causing hepatitis. Although isoniazid is the main culprit causing hepatic injury, role of other drugs is also there previous studies conducted have proven that the risk is in the order of isoniazide+rifampicin greater than isoniazid. Isoniazid greater than pyrazinamide. pyrazinamide greater than rifampicin. rifampicin greater than ethambutol.24 This studies were done by garibaldi R, Drusinr, frebbes, gregg m.

 

CONCLUSION

Correlation between age, sex and incidence of ATT induced hepatitis is controversial and requires further studies. In our study occurrence was more in young males. Correlation between incidence of ATT induced hepatitis and nutrition is controversial and it is more in common in people with low BMI in our study. Chronic alcoholism is not an independent risk factor. However history of prior alcohol induced hepatitis or alcohol induced liver disease has been well established as risk factor for drug induced hepatitis.

 

REFERENCES

  1. World Health Organization, Global Tuberculousis CONTROL. WHO report, 2001. geneva Switzerland: WHO/CDS/TB, 2001.287.
  2. Mahashur AA, Prabhudesai PP. Hepatitis and antitubercular therapy. J Assocphysicians India 1991; 39: 595-6.
  3. Govt. Of India (2006), Annual Report 2005-2006, Ministry Of Health and Family Welfare, New delhi
  4. Govt. Of India (2006), T.B. India 2006, RNTCP status report, DOT’s for All for DOT’s Ministry Of Health and Family Welfare, New Delhi.
  5. Vidal R, Rey R, Espnar A, et al. treatment and retreatment of tuberculosis. Arch Bronconeumol 1996: 32: 463-474.
  6. Pande J N, singh S P, Khilnani G C, Khilnani S, Tandon R K. Risk factors for hepatotoxicity from antituberculosis drugs: a case-control study. Thorax 1996; 51: 132-136.
  7. American thoracic society, centres for disease control and prevention and infectious disease society of America: treatment of tuberculosis. Am J respirecrity care med 2003; 167: 603-662.
  8. Gronhagen – Riska, C., P.E. Hellstrom, and B. froseth. 1978. Predisposing factors in hepatitis induced by isoniazid-rifampicin treatment of tuberculosis. Am. Rev. Respir. Dis 118: 461-466.
  9. Teleman MD, Chee CB, Earnest A, Wang YT. Hepatotoxicity of Tuberculosis chemotherapy under general conditions in Singapore. Int J Tuberc Lung Dis 2000; 6: 699-705.
  10. Sharma S K, Balamurugan A, Saha P K, Pandey R M, Mehra N K. evaluation of clinical and immuunogenetic risk factors for the development of hepatotoxicity during antituberculosis treatment. Am J RespirCrit Care Med 2002; 166-119.
  11. Pande J N, singh S P, Khilnani G C, Khilnani S, Tandon R K. Risk factors for hepatotoxicity from antituberculosis drugs: a case-control study. Thorax 1996; 51: 132-136
  12. Huang Y S, Chern H D, Su W J, et al. polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug induced hepatitis. Hepatology 2002; 35:885-889.
  13. Devoto F M, Gonzalez C, lannantuono R, Serra H A, Gonazalez; C D, Saenz acta. PhysiolPharmacolTherLatinoam; 1997; 47: 197-202.
  14. Gilrory S A, Rogers M A, Blair D C. Treatment of Latent Tuberculosis infection in patients aged. 35 years. Clin Infect Dis. 2000; 31: 826-829.
  15. Stevens, C.E., P.E. Taylor, J. Pindyck, Q.L. Choo, D.W. Bradley, G. Kuo, and M. Houghlon. 1990. Epidemiology of hepatitis C virus: a preliminary study in volunteer blood donors. J.A.M.A. 263: 49-53.
  16. Alter, M. J., 1994. Transmission of hepatitis C virus: route, dose and titer, N. Engl. J. Med. 330L 784
  17. Bailey, W.C., S.L. Taylor, H.E. Dascomb, H.B. Greenberg, and M.M. Ziskind. 1973. Disturbed hepatic function during isoniazid chemoprophylaxis. Am. Rev. Respir. Dis. 107: 523-529.
  18. Taneja DP, Kaur D. Desprez RM. Hepatitis with isoniazid and rifampicin; antituberculosis drugs. J Indian med assoc 1990; 88:278-80.
  19. Gurumurthy p, Krishnamurthy MS, Nazareth O, et al. Lack of relationship between hepatic toxicity and acetylator phenotype in three thousand south Indian patients during treatment with isoniazid for tuberculosis. Am Rev Respir Dis 1984; 129:58-61.
  20. Wong WM, Wu PC, Yuen MF, et al. antituberculosis drug related liver dysfunction in chronic hepatitis B infection. Hepatology 2000; 3; 201-206.
  21. Deshpande DV, Nachne D, Koyande D, Rodrigues CJ. Antitubercular Physicians india 1991; 39: 599-601.
  22. Singh J, Garg PK, Tandon RK, Hepatotxicity due to antituberculosis therapy. Clinical profile and reintroduction of therapy. J ClinGastroenterology 1996; 22(3): 211-4.
  23. Taneja DP, Kaur D. Desprez RM. Hepatitis with isoniazid and rifampicin; antituberculosis drugs. J Indian med assoc 1990; 88:278-80.
  24. Steele MA, Burk RF, Desprez RM. Hepatitis with insoniazid and rifampicin; a meta-analysis. Chest 1991; 99:465-71.
  25. Kopanoff DE, Snider D, Caras G. Isoniazid related hepatitis: a U.S. Public Health Service Cooperative surveillance study. Am. Rev. Respir. Dis; 1979; 117: 991-1001.

 



 









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