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Published in: BMC Infectious Diseases 1/2018

Open Access 01-12-2018 | Research article

Co-infection with hepatitis B virus among tuberculosis patients is associated with poor outcomes during anti-tuberculosis treatment

Authors: Lubiao Chen, Dujing Bao, Lin Gu, Yurong Gu, Liang Zhou, Zhiliang Gao, Yuehua Huang

Published in: BMC Infectious Diseases | Issue 1/2018

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Abstract

Background

Tuberculosis (TB) and chronic Hepatitis B virus (HBV) infection are common in China. Fist-line anti-TB medications often produce drug-induced liver injury (DILI). This study sought to investigate whether TB patients with chronic HBV co-infection are more susceptible to liver failure and poor outcomes during anti-TB treatment.

Methods

Eighty-four TB patients developed DILI during anti-TB treatment and were enrolled, including 58 with chronic HBV co-infection (TB-HBV group) and 26 with TB mono-infection (TB group). Clinical data and demographic characteristics were reviewed. The severity of DILI and incidences of liver failure and death were compared. Risk factors of clinical outcomes were defined.

Results

The patterns of DILI were similar in both groups. Compared with patients in the TB group, patients in the TB-HBV group who did not receive anti-HBV therapy before anti-TB treatment were more susceptible to Grade-4 severity of DILI (36.2% vs. 7.7%, P = 0.005), liver failure (67.2% vs. 38.5%, P = 0.013) and poor outcomes (37.9% vs. 7.7%, P = 0.005). Age > 50 years (48.1% vs. 22.6%, P = 0.049), cirrhosis (50.0% vs. 15.4%, P = 0.046) and total bilirubin > 20 mg/dl (51.6% vs. 14.8%, P = 0.005) were independent risk factors for the rate of death in the TB-HBV group, and HBV DNA > 20,000 IU/ml had borderline significance (44.1% vs. 20.8%, P = 0.081). In the TB-HBV group, nucleos(t)ide analogues as rescue therapy were not able to reduce short-term death (33.3% vs. 36.8%, P = 0.659) once liver failure had occurred.

Conclusions

Patients on anti-TB therapy with chronic HBV co-infection are more susceptible to developing liver failure and having poor outcomes during anti-TB treatment. Regular monitoring of liver function and HBV DNA level is mandatory. Anti-HBV treatment should be considered in those with high viral levels before anti-TB treatment.
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Literature
2.
go back to reference Wang LX, Chen SM, Chen MT, et al. The fifth national tuberculosis epidemiological survey in 2010 [Chinese]. Chin J Antibiot. 2012;34(8):485–508. Wang LX, Chen SM, Chen MT, et al. The fifth national tuberculosis epidemiological survey in 2010 [Chinese]. Chin J Antibiot. 2012;34(8):485–508.
3.
go back to reference Chinese Society of Hepatology. Chinese Medical Association, Chinese Society of Infectious Diseases, Chinese Medical Association. The guideline of prevention and treatment for chronic hepatitis B: a 2015 update [Chinese]. Zhonghua Gan Zang Bing Za Zhi. 2015;3(12):888–905. Chinese Society of Hepatology. Chinese Medical Association, Chinese Society of Infectious Diseases, Chinese Medical Association. The guideline of prevention and treatment for chronic hepatitis B: a 2015 update [Chinese]. Zhonghua Gan Zang Bing Za Zhi. 2015;3(12):888–905.
4.
go back to reference Sharma SK, Balamurugan A, Saha PK, Pandey RM, Mehra NK. Evaluation of clinical and immunogenetic risk factors for the development of hepatotoxicity during antituberculosis treatment. Am J Respir Crit Care Med. 2002;166(7):916–9.CrossRefPubMed Sharma SK, Balamurugan A, Saha PK, Pandey RM, Mehra NK. Evaluation of clinical and immunogenetic risk factors for the development of hepatotoxicity during antituberculosis treatment. Am J Respir Crit Care Med. 2002;166(7):916–9.CrossRefPubMed
5.
go back to reference van Hest R, Baars H, Kik S, et al. Hepatotoxicity of rifampin-pyrazinamide and isoniazid preventive therapy and tuberculosis treatment. Clin Infect Dis. 2004;39(4):488–96.CrossRefPubMed van Hest R, Baars H, Kik S, et al. Hepatotoxicity of rifampin-pyrazinamide and isoniazid preventive therapy and tuberculosis treatment. Clin Infect Dis. 2004;39(4):488–96.CrossRefPubMed
6.
go back to reference Sharifzadeh M, Rasoulinejad M, Valipour F, Nouraie M, Vaziri S. Evaluation of patient-related factors associated with causality, preventability, predictability and severity of hepatotoxicity during antituberculosis treatment. Pharmacol Res. 2005;51(4):353–8.CrossRefPubMed Sharifzadeh M, Rasoulinejad M, Valipour F, Nouraie M, Vaziri S. Evaluation of patient-related factors associated with causality, preventability, predictability and severity of hepatotoxicity during antituberculosis treatment. Pharmacol Res. 2005;51(4):353–8.CrossRefPubMed
7.
go back to reference Tost JR, Vidal R, Caylà J, et al. Severe hepatotoxicity due to anti-tuberculosis drugs in Spain. Int J Tuberc Lung Dis. 2005;9(5):534–40.PubMed Tost JR, Vidal R, Caylà J, et al. Severe hepatotoxicity due to anti-tuberculosis drugs in Spain. Int J Tuberc Lung Dis. 2005;9(5):534–40.PubMed
8.
go back to reference Bertoletti A, Kennedy PT. The immune tolerant phase of chronic HBV infection: new perspectives on an old concept. Cell Mol Immunol. 2015;12(3):258–63.CrossRefPubMed Bertoletti A, Kennedy PT. The immune tolerant phase of chronic HBV infection: new perspectives on an old concept. Cell Mol Immunol. 2015;12(3):258–63.CrossRefPubMed
9.
go back to reference Pan L, Jia ZS, Chen L, et al. Effect of anti-tuberculosis therapy on liver function of pulmonary tuberculosis patients infected with hepatitis B virus. World J Gastroenterol. 2005;11(16):2518–21.CrossRefPubMedPubMedCentral Pan L, Jia ZS, Chen L, et al. Effect of anti-tuberculosis therapy on liver function of pulmonary tuberculosis patients infected with hepatitis B virus. World J Gastroenterol. 2005;11(16):2518–21.CrossRefPubMedPubMedCentral
10.
go back to reference Patel PA, Voigt MD. Prevalence and interaction of hepatitis B and latent tuberculosis in Vietnamese immigrants to the United States. Am J Gastroenterol. 2002;97:1198–2203. Patel PA, Voigt MD. Prevalence and interaction of hepatitis B and latent tuberculosis in Vietnamese immigrants to the United States. Am J Gastroenterol. 2002;97:1198–2203.
11.
go back to reference Aithal GP, Watkins PB, Andrade RJ, et al. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther. 2011;89(6):806–15. Aithal GP, Watkins PB, Andrade RJ, et al. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther. 2011;89(6):806–15.
12.
go back to reference Danan G, Benichou C. Causality assessment of adverse reactions to drugs I. A novel method based on the conclusions of international consensus meetings: application to drug induced liver injuries. J Clin Epidemiol. 1993;46(11):1323–30.CrossRefPubMed Danan G, Benichou C. Causality assessment of adverse reactions to drugs I. A novel method based on the conclusions of international consensus meetings: application to drug induced liver injuries. J Clin Epidemiol. 1993;46(11):1323–30.CrossRefPubMed
13.
go back to reference Chalasani NP, Hayashi PH, Bonkovsky HL, Navarro VJ, Lee WM, Fontana RJ. Practice Parameters Committee of the American College of Gastroenterology. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2014;109(7):950–66.CrossRefPubMed Chalasani NP, Hayashi PH, Bonkovsky HL, Navarro VJ, Lee WM, Fontana RJ. Practice Parameters Committee of the American College of Gastroenterology. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2014;109(7):950–66.CrossRefPubMed
15.
go back to reference Sarin SK, Kedarisetty CK, Abbas Z, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL) 2014. Hepatol Int. 2014;8(4):453–71.CrossRefPubMed Sarin SK, Kedarisetty CK, Abbas Z, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL) 2014. Hepatol Int. 2014;8(4):453–71.CrossRefPubMed
16.
go back to reference Hung CH, Lu SN, Wang JH, et al. Correlation between ultrasonographic and pathologic diagnoses of hepatitis B and C virus-related cirrhosis. J Gastroenterol. 2003;38(2):153–7.CrossRefPubMed Hung CH, Lu SN, Wang JH, et al. Correlation between ultrasonographic and pathologic diagnoses of hepatitis B and C virus-related cirrhosis. J Gastroenterol. 2003;38(2):153–7.CrossRefPubMed
17.
go back to reference Wang JY, Liu CH, Hu FC, et al. Risk factors of hepatitis during anti-tuberculous treatment and implications of hepatitis virus load. J Inf Secur. 2011;62(6):448–55. Wang JY, Liu CH, Hu FC, et al. Risk factors of hepatitis during anti-tuberculous treatment and implications of hepatitis virus load. J Inf Secur. 2011;62(6):448–55.
18.
go back to reference Wong WM, Wu PC, Yuen MF, et al. Antituberculosis drug-related liver dysfunction in chronic hepatitis B infection. Hepatology. 2000;31(1):201–6.CrossRefPubMed Wong WM, Wu PC, Yuen MF, et al. Antituberculosis drug-related liver dysfunction in chronic hepatitis B infection. Hepatology. 2000;31(1):201–6.CrossRefPubMed
19.
go back to reference Knowles SR, Uetrecht J, Shear NH. Idiosyncratic drug reactions: the reactive metabolite syndromes. Lancet. 2000;356(9241):1587–91.CrossRefPubMed Knowles SR, Uetrecht J, Shear NH. Idiosyncratic drug reactions: the reactive metabolite syndromes. Lancet. 2000;356(9241):1587–91.CrossRefPubMed
20.
go back to reference Metushi IG, Cai P, Zhu X, Nakagawa T, Uetrecht JP. A fresh look at the mechanism of isoniazid-induced hepatotoxicity. Clin Pharmacol Ther. 2011;89(6):911–4.CrossRefPubMed Metushi IG, Cai P, Zhu X, Nakagawa T, Uetrecht JP. A fresh look at the mechanism of isoniazid-induced hepatotoxicity. Clin Pharmacol Ther. 2011;89(6):911–4.CrossRefPubMed
21.
go back to reference Ramappa V, Aithal GP. Hepatotoxicity related to anti-tuberculosis drugs: mechanisms and management. J Clin Exp Hepatol. 2013;3(1):37–49.CrossRefPubMed Ramappa V, Aithal GP. Hepatotoxicity related to anti-tuberculosis drugs: mechanisms and management. J Clin Exp Hepatol. 2013;3(1):37–49.CrossRefPubMed
22.
go back to reference Pirmohamed M, Naisbitt DJ, Gordon F, Park BK. The danger hypothesis-potential role in idiosyncratic drug reactions. Toxicology. 2002;181-182:55–63.CrossRefPubMed Pirmohamed M, Naisbitt DJ, Gordon F, Park BK. The danger hypothesis-potential role in idiosyncratic drug reactions. Toxicology. 2002;181-182:55–63.CrossRefPubMed
23.
go back to reference European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol. 2012;57(1):167–85.CrossRef European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol. 2012;57(1):167–85.CrossRef
24.
go back to reference Yuen MF. Anti-viral therapy in hepatitis B virus reactivation with acute-on-chronic liver failure. Hepatol Int. 2015;9(3):373–7.CrossRefPubMed Yuen MF. Anti-viral therapy in hepatitis B virus reactivation with acute-on-chronic liver failure. Hepatol Int. 2015;9(3):373–7.CrossRefPubMed
25.
go back to reference Philips CA, Sarin SK. Potent antiviral therapy improves survival in acute on chronic liver failure due to hepatitis B virus reactivation. World J Gastroenterol. 2014;20(43):16037–52.CrossRefPubMedPubMedCentral Philips CA, Sarin SK. Potent antiviral therapy improves survival in acute on chronic liver failure due to hepatitis B virus reactivation. World J Gastroenterol. 2014;20(43):16037–52.CrossRefPubMedPubMedCentral
26.
go back to reference Zhang Y, Hu XY, Zhong S, et al. Entecavir vs lamivudine therapy for naïve patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure. World J Gastroenterol. 2014;20(16):4745–52.CrossRefPubMedPubMedCentral Zhang Y, Hu XY, Zhong S, et al. Entecavir vs lamivudine therapy for naïve patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure. World J Gastroenterol. 2014;20(16):4745–52.CrossRefPubMedPubMedCentral
27.
go back to reference Fountain FF, Tolley E, Chrisman CR, Self TH. Isoniazid hepatotoxicity associated with treatment of latent tuberculosis infection: a 7-year evaluation from a public health tuberculosis clinic. Chest. 2005;128(1):116–23.CrossRefPubMed Fountain FF, Tolley E, Chrisman CR, Self TH. Isoniazid hepatotoxicity associated with treatment of latent tuberculosis infection: a 7-year evaluation from a public health tuberculosis clinic. Chest. 2005;128(1):116–23.CrossRefPubMed
28.
go back to reference Vlachogiannakos J, Papatheodoridis GV. HBV: Do I treat my immunotolerant patients? Liver Int. 2016;36(Suppl 1):93–9.CrossRefPubMed Vlachogiannakos J, Papatheodoridis GV. HBV: Do I treat my immunotolerant patients? Liver Int. 2016;36(Suppl 1):93–9.CrossRefPubMed
30.
go back to reference Qu YW, Guo Y, Zhao GD, He HZ, Liu Y. The mechanism and prevention of hepatic damage caused by anti-TB drug [Chinese]. Zhongguo Fanglao Zazhi. 2001;23:56–7. Qu YW, Guo Y, Zhao GD, He HZ, Liu Y. The mechanism and prevention of hepatic damage caused by anti-TB drug [Chinese]. Zhongguo Fanglao Zazhi. 2001;23:56–7.
31.
go back to reference van den Brande P, van Steenbergen W, Vervoort G, Demedts M. Aging and hepatotoxicity of isoniazid and rifampin inpulmonary tuberculosis. Am J Respir Crit Care Med. 1995;152(5):1705–8.CrossRefPubMed van den Brande P, van Steenbergen W, Vervoort G, Demedts M. Aging and hepatotoxicity of isoniazid and rifampin inpulmonary tuberculosis. Am J Respir Crit Care Med. 1995;152(5):1705–8.CrossRefPubMed
32.
go back to reference Huang YH, Hsiao LT, Hong YC, et al. Randomized controlled trial of entecavir prophylaxis for rituximab-associated hepatitis B virus reactivation in patients with lymphoma and resolved hepatitis B. J Clin Oncol. 2013;31(22):2765–72.CrossRefPubMed Huang YH, Hsiao LT, Hong YC, et al. Randomized controlled trial of entecavir prophylaxis for rituximab-associated hepatitis B virus reactivation in patients with lymphoma and resolved hepatitis B. J Clin Oncol. 2013;31(22):2765–72.CrossRefPubMed
33.
go back to reference Huang H, Li X, Zhu J, et al. Entecavir vs lamivudine for prevention of hepatitis B virus reactivation among patients with untreated diffuse large B-cell lymphoma receiving R-CHOP chemotherapy: a randomized clinical trial. JAMA. 2014;312(23):2521–30.CrossRefPubMed Huang H, Li X, Zhu J, et al. Entecavir vs lamivudine for prevention of hepatitis B virus reactivation among patients with untreated diffuse large B-cell lymphoma receiving R-CHOP chemotherapy: a randomized clinical trial. JAMA. 2014;312(23):2521–30.CrossRefPubMed
34.
go back to reference Trigo C, do Brasil PE, Costa MJ, de Castro L. Occult hepatitis B virus infection: clinical implications in tuberculosis treatment. J Viral Hepat. 2016;23(12):1027–35.CrossRefPubMed Trigo C, do Brasil PE, Costa MJ, de Castro L. Occult hepatitis B virus infection: clinical implications in tuberculosis treatment. J Viral Hepat. 2016;23(12):1027–35.CrossRefPubMed
Metadata
Title
Co-infection with hepatitis B virus among tuberculosis patients is associated with poor outcomes during anti-tuberculosis treatment
Authors
Lubiao Chen
Dujing Bao
Lin Gu
Yurong Gu
Liang Zhou
Zhiliang Gao
Yuehua Huang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2018
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-018-3192-8

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