Intrapartum and Postpartum Reactivation of Hepatitis B in Pregnant Patients: a multicentre study
Reactivación intraparto y posparto de la hepatitis B en pacientes embarazadas: un estudio multicéntrico
Fethiye Akgül, Ahmet Şahin, Yeliz Çiçek, Esra Gürbüz, Mehmet Çelik, Yusuf Arslan, Ömer Karaşahin, Mehmet Reşat Ceylan
Abstract
Introduction: Changes in the immune system during pregnancy have been associated with reactivation of the hepatitis B virus in women chronic hepatitis B infection not receiving antiviral therapy. The aim of this study is to examine the development of intrapartum and postpartum hepatitis B reactivation in pregnant patients not being treated for chronic hepatitis B.
Material and Methods: Pregnant women diagnosed with chronic hepatitis B and not receiving treatment between 2017 and 2022 in five centres in the east and southeast Turkey included in this study. In order to evaluate biochemical and viral reactivation from intrapartum and postpartum periods, patients with data for at least two periods were included in the study.
Results: Evaluations were made on 171 pregnant women diagnosed with chronic hepatitis B. Reactivation occurred in 43 (25.2%) patients, in the postpartum period in 14 (32.35%) and in the intrapartum period in 29 (67.44%). Reactivation occurred most often in the 3rd trimester (n: 13, 30.2%). A significant increase was observed in the alanine aminotransferase levels of the patients with reactivation in the first trimester compared to 6 months prepartum and in the second trimester compared to the first trimester (p=0.038, p=0.039, respectively). The prepartum HBV DNA level (cut-off point =192 IU/ml) of patients with HBeAg negativity was found to have diagnostic power for reactivation of 0.684 (95% CI: 0.575-0.792, p=0.002) with 65.9% sensitivity and 68.6% specificity. Viral reactivation was observed in the first trimester in one patient and hepatitis B surface antibody was seen in the postpartum period.
Conclusions: Asymptomatic viral reactivation occurred at the high rate of 25.1% in this series. To be able to identify reactivation as early as possible, pregnant patients should be followed up closely in the intrapartum and postpartum periods.
Keywords
Resumen
Introducción: Los cambios en el sistema inmunológico durante el embarazo se han asociado con la reactivación del virus de la hepatitis B en mujeres con infección crónica por hepatitis B que no reciben terapia antiviral. El objetivo de este estudio es examinar el desarrollo de la reactivación de la hepatitis B intraparto y posparto en pacientes embarazadas que no reciben tratamiento para la hepatitis B crónica.
Material y Métodos: Mujeres embarazadas diagnosticadas de hepatitis B crónica y que no recibieron tratamiento entre 2017 y 2022 en cinco centros del este y sureste de Turquía incluidos en este estudio. Para evaluar la reactivación bioquímica y viral de los períodos intraparto y posparto, se incluyeron en el estudio pacientes con datos de al menos dos períodos.
Resultados: Se evaluaron 171 gestantes con diagnóstico de hepatitis B crónica. La reactivación ocurrió en 43 (25,2%) pacientes, en el puerperio en 14 (32,35%) y en el intraparto en 29 (67,44%). La reactivación ocurrió con mayor frecuencia en el tercer trimestre (n: 13, 30,2%). Se observó un aumento significativo en los niveles de alanina aminotransferasa de las pacientes con reactivación en el primer trimestre en comparación con los 6 meses preparto y en el segundo trimestre en comparación con el primer trimestre (p = 0,038, p = 0,039, respectivamente). Se encontró que el nivel de ADN del VHB antes del parto (punto de corte = 192 UI/ml) de pacientes con HBeAg negativo tenía un poder diagnóstico para la reactivación de 0,684 (IC del 95 %: 0,575-0,792, p = 0,002) con una sensibilidad del 65,9 % y una sensibilidad del 68,6 %. % especificidad. Se observó reactivación viral en el primer trimestre en una paciente y se observaron anticuerpos de superficie contra la hepatitis B en el período posparto.
Conclusiones: La reactivación viral asintomática ocurrió en la alta tasa de 25,1% en esta serie. Para poder identificar la reactivación lo antes posible, las pacientes embarazadas deben ser seguidas de cerca en los períodos intraparto y posparto.
Palabras clave
References
1. Ratnam D, Visvanathan K. New concepts in the immunopathogenesis of chronic hepatitis B: the importance of the innate immune response. Hepatol Int. 2008;2(Supplement 1):12-8. doi: 10.1007/s12072-008-9067-0.
2. Mohite BJ, Rath S, Bal V, Kamat SA, Marathe SN, Zuckerman AJ, et al. Mechanisms of liver cell damage in acute hepatitis B. J Med Virol. 1987;22(3):199-210. doi: 10.1002/jmv.1890220302.
3. Liaw YF. Hepatitis flares and hepatitis B e antigen seroconversion: implication in anti-hepatitis B virus therapy. J Gastroenterol Hepatol. 2003;18(3):246-52. doi: 10.1046/j.1440-1746.2003.02976.x.
4. Kumar M, Abbas Z, Azami M, Belopolskaya M, Dokmeci AK, Ghazinyan H, et al. Asian Pacific association for the study of liver (APASL) guidelines: hepatitis B virus in pregnancy. Hepatol Int. 2022;16(2):211-53. doi: 10.1007/s12072-021-10285-5.
5. Malekifar P, Babanejad M, Izadi N, Alavian SM. The frequency of HBsAg in pregnant women from eastern mediterranean and middle eastern countries: A systematic review and meta-analysis. Hepat Mon. 2018;18(9): e58830. doi: 10.5812/hepatmon.58830.
6. Piratvisuth T. Optimal management of HBV infection during pregnancy. Liver Int. 2013;33 Suppl 1:188-94. doi: 10.1111/liv.12060.
7. Singhal A, Kanagala R, Jalil S, Wright HI, Kohli V. Chronic HBV with pregnancy: reactivation flare causing fulminant hepatic failure. Ann Hepatol. 2011;10(2):233-6.
8. Nguyen G, Garcia RT, Nguyen N, Trinh H, Keeffe EB, Nguyen MH. Clinical course of hepatitis B virus infection during pregnancy. Aliment Pharmacol Ther. 2009;29(7):755-64. doi: 10.1111/j.1365-2036.2009.03932.x.
9. Lau G, Yu ML, Wong G, Thompson A, Ghazinian H, Hou JL, et al. APASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy. Hepatol Int. 2021;15(5):1031-48. doi: 10.1007/s12072-021-10239-x.
10. Aygen B, Demir AM, Gümüş M, Karabay O, Kaymakoğlu S, Köksal AŞ, et al. Immunosuppressive therapy and the risk of hepatitis B reactivation: Consensus report. Turk J Gastroenterol. 2018;29(3):259-69. doi: 10.5152/tjg.2018.18263.
11. Elefsiniotis I, Vezali E, Vrachatis D, Hatzianastasiou S, Pappas S, Farmakidis G, et al. Post-partum reactivation of chronic hepatitis B virus infection among hepatitis B e-antigen-negative women. World J Gastroenterol. 2015;21(4):1261-7. doi: 10.3748/wjg.v21.i4.1261.
12. Bzowej NH, Tran TT, Li R, Belle SH, Smith CI, Khalili M, et al. Total Alanine Aminotransferase (ALT) Flares in Pregnant North American Women With Chronic Hepatitis B Infection: Results From a Prospective Observational
Study. Am J Gastroenterol. 2019;114(8):1283-91. doi: 10.14309/ajg.0000000000000221.
13. Zou H, Chen Y, Duan Z, Zhang H, Pan C. Virologic factors associated with failure to passive-active immunoprophylaxis in infants born to HBsAg-positive mothers. J Viral Hepat. 2012;19(2):e18-25. doi: 10.1111/j.1365-2893.2011.01492.x.
14. Pan CQ, Duan ZP, Bhamidimarri KR, Zou HB, Liang XF, Li J, et al. An algorithm for risk assessment and intervention of mother to child transmission of hepatitis B virus. Clin Gastroenterol Hepatol. 2012;10(5):452-9. doi: 10.1016/j.cgh.2011.10.041.
15. Borgia G, Carleo MA, Gaeta GB, Gentile I. Hepatitis B in pregnancy. World J Gastroenterol. 2012;18(34):4677-83. doi: 10.3748/wjg.v18.i34.4677.
16. Han GR, Xu CL, Zhao W, Yang YF. Management of chronic hepatitis B in pregnancy. World J Gastroenterol. 2012;18(33):4517-21. doi: 10.3748/wjg.v18.i33.4517.
17. Tran TT. Management of hepatitis B in pregnancy: weighing the options. Cleve Clin J Med. 2009;76 Suppl 3:S25-9. doi: 10.3949/ccjm.76.s3.06.
18. Bzowej NH. Optimal Management of the Hepatitis B Patient Who Desires Pregnancy or Is Pregnant. Curr Hepat Rep. 2012;11(2):82-9. doi: 10.1007/s11901-012-0130-x.
19. ter Borg MJ, Leemans WF, de Man RA, Janssen HL. Exacerbation of chronic hepatitis B infection after delivery. J Viral Hepat. 2008;15(1):37-41. doi: 10.1111/j.1365-2893.2007.00894.x.
20. Söderström A, Norkrans G, Lindh M. Hepatitis B virus DNA during pregnancy and post partum: aspects on vertical transmission. Scand J Infect Dis. 2003;35(11-12):814-9. doi: 10.1080/00365540310016547.
21. Wang X, Song A, Lin X, Lu J, Zheng S, Ma L, et al. Clinical characteristics of hepatitis flares during pregnancy and postpartum in Chinese chronic hepatitis B virus carriers-a prospective cohort study of 417 cases. Front Immunol. 2022;13:1031291. doi: 10.3389/fimmu.2022.1031291.
22. Li L, Zou H, Xu M, Li S, Zhu Y, Zheng S, et al. Risk factors related to postpartum hepatic inflammation in pregnant women with chronic hepatitis B. J Int Med Res. 2020;48(11):300060520966439. doi: 10.1177/0300060520966439.
23. Tan HH, Lui HF, Chow WC. Chronic hepatitis B virus (HBV) infection in pregnancy. Hepatol Int. 2008;2(3):370-5. doi: 10.1007/s12072-008-9063-4.
24. Giles M, Visvanathan K, Lewin S, Bowden S, Locarnini S, Spelman T, et al. Clinical and virological predictors of hepatic flares in pregnant women with chronic hepatitis B. Gut. 2015;64(11):1810-5. doi: 10.1136/gutjnl-2014-308211.
25. Lu H, Cao W, Zhang L, Yang L, Bi X, Lin Y, et al. Effects of hepatitis B virus infection and strategies for preventing mother-to-child transmission on maternal and fetal T-cell immunity. Front Immunol. 2023;14:1122048. doi: 10.3389/fimmu.2023.1122048.
26. Samadi Kochaksaraei G, Castillo E, Osman M, Simmonds K, Scott AN, Oshiomogho JI, et al. Clinical course of 161 untreated and tenofovir-treated chronic hepatitis B pregnant patients in a low hepatitis B virus endemic region. J Viral Hepat. 2016;23(1):15-22. doi: 10.1111/jvh.12436.
27. Chang CY, Aziz N, Poongkunran M, Javaid A, Trinh HN, Lau D, et al. Serum Alanine Aminotransferase and Hepatitis B DNA Flares in Pregnant and Postpartum Women with Chronic Hepatitis B. Am J Gastroenterol. 2016;111(10):1410-5. doi: 10.1038/ajg.2016.296.
28. Kim HY, Choi JY, Park CH, Jang JW, Kim CW, Bae SH, et al. Outcome after discontinuing antiviral agents during pregnancy in women infected with hepatitis B virus. J Clin Virol. 2013;56(4):299-305. doi: 10.1016/j.jcv.2012.11.019.
Submitted date:
04/26/2023
Reviewed date:
05/29/2023
Accepted date:
06/21/2023
Publication date:
06/23/2023
Facebook
Google+
Twitter
LinkedIn
Mendeley
StumbleUpon
CiteULike
Reddit
Email