Early plasma exchange and continuous renal replacement therapy improve puerperal prognosis in hepatitis B virus-related acute-on-chronic liver failure in pregnancy

Abstract

Background and aim: Hepatitis B virus (HBV)-related gestational acute-on-chronic liver failure (ACLF) is a severe condition with limited treatment options. This study aimed to evaluate the efficacy and ideal timing of plasma exchange and continuous renal replacement therapy (CRRT) in managing pregnant women with HBV-related ACLF.

Methods: This study retrospectively analyzed 51 eligible patients with HBV-related gestational ACLF between 2009 and 2020. Patients admitted to the study were divided into a conventional treatment group and a new treatment group according to whether they received the new management protocol, which included more aggressive plasma exchange (PE) and CRRT strategies. All 19 pregnant women with hepatic encephalopathy (HE) were divided into an early treatment group and a non-early treatment group according to whether PE therapy was initiated within three days. Our study had two primary objectives. Firstly, we aimed to evaluate the impact of PE and CRRT on puerperal survival. Secondly, we sought to assess the effects of early PE and CRRT regimens on puerperal survival in women with HE.

Results: The levels of total bilirubin on the second day postpartum (D3), the third day postpartum (D4), and the fifth day postpartum (D6) were significantly lower in the new treatment group compared to the conventional treatment group (P = 0.02, 0.01, and 0.02, respectively). The ALT of D3 was significantly elevated in the new treatment group compared to the conventional treatment group (P = 0.02). The incidence of HE overall increased from prenatal to postpartum D4, peaked on D4, and then gradually decreased from the fourth day postpartum (D5) (P = 0.027). The first week after delivery revealed a significant difference in survival rate between the two groups, the conventional treatment group had statistically higher mortality rates compared to the new treatment group (P = 0.002). Similarly, the entire puerperal period mortality rate of the conventional treatment group was statistically higher than the new treatment group (P = 0.002). Moreover, among all patients with HE, the non-early treatment group showed significantly higher puerperal mortality rates compared to the early treatment group (P = 0.006).

Conclusions: Early PE and CRRT conducted within three days post-childbirth, enhance puerperal prognosis for HBV-related gestational ACLF.

Keywords

Acute-on-chronic liver failure (ACLF) / Liver disease in pregnancy / Hepatitis B virus (HBV) / Plasma exchange (PE) / Continuous renal replacement therapy (CRRT) / Hepatic encephalopathy (HE)

Data availability statement

The data that support the findings of this study are available on request from the corresponding author, Xuxia Wei, upon reason-able request.

Authors’ contributions

Lijuan Li and Mingming Fan contributed equally to this work and should be considered co-first authors. Lijuan Li: Conceptualization, Data curation, Formal analysis, Methodology, Writing e original draft. Mingming Fan: Conceptualization, Data curation, Formal analysis, Writing e original draft. Mi Zhou: Data curation, Software, Supervision. Pinglan Lu: Data curation, Supervision, Validation. Jianrong Liu: Project administration, Resources, Software. Huimin Yi: Funding acquisition, Writing e review & editing. Xuxia Wei: Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Writing e review & editing.

Declaration of competing interest

The authors declare that there is no conflicts of interest.

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (NO. 82270690) to Huimin Yi, the National Natural Science Foundation of China (NO. 82200732) to Xuxia Wei, the Guangdong Natural Science foundation (NO. 2022A1515012519) to Xuxia Wei, and the Guangdong Natural Sci-ence foundation (NO. 2022A1515011919) to Huimin Yi.

References

[1] Sarin SK, Kumar A, Almeida JA, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL). Hepatol Int. 2009;3:269-282. https://doi.org/10.1007/s12072-008-9106-x.

[2] Sarin SK, Choudhury A, Sharma MK, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL): an update. Hepatol Int. 2019;13:353-390. https://doi.org/10.1007/s12072-019-09946-3.

[3] 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;8:453-471. https://doi.org/10.1007/s12072-014-9580-2.

[4] Jalan R, Yurdaydin C, Bajaj JS, et al. Toward an improved definition of acute-on-chronic liver failure. Gastroenterology. 2014;147:4-10. https://doi.org/10.1053/j.gastro.2014.05.005.

[5] Wu T, Li J, Shao L, et al. Development of diagnostic criteria and a prognostic score for hepatitis B virus-related acute-on-chronic liver failure. Gut. 2018;67: 2181-2191. https://doi.org/10.1136/gutjnl-2017-314641.

[6] Wlodzimirow KA, Eslami S, Abu-Hanna A, Nieuwoudt M, Chamuleau RA. A systematic review on prognostic indicators of acute on chronic liver failure and their predictive value for mortality. Liver Int. 2013;33:40-52. https://doi.org/10.1111/j.1478-3231.2012.02790.x.

[7] Laleman W, Verbeke L, Meersseman P, et al. Acute-on-chronic liver failure: current concepts on definition, pathogenesis, clinical manifestations and po-tential therapeutic interventions. Expet Rev Gastroenterol Hepatol. 2011;5: 523-537. https://doi.org/10.1586/egh.11.47.

[8] Jalil S, Elfeki MA, Kiefer MK, Kuo YF, Singal AK. Waitlist and posttransplant outcomes of pregnancy-related acute liver failure in the United States. Liver Transpl. 2024;30:573-581. https://doi.org/10.1097/LVT.0000000000000319.

[9] Steven MM, Buckley JD, Mackay IR. Pregnancy in chronic active hepatitis. QJ Med. 1979;48:519-531.

[10] van der Slink LL, Scholten I, van Etten-Jamaludin FS, Takkenberg RB, Painter RC. Pregnancy in women with liver cirrhosis is associated with increased risk for complications: a systematic review and meta-analysis of the literature. BJOG. 2022;129:1644-1652. https://doi.org/10.1111/1471-0528.17156.

[11] Ibrahim SH, Jonas MM, Taylor SA, Gutierrez Sanchez LH, Wolf JL, Sundaram SS. Liver diseases in the perinatal period: interactions between mother and infant. Hepatology. 2020;71:1474-1485. https://doi.org/10.1002/hep.31109.

[12] European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of liver diseases in pregnancy. J Hepatol. 2023;79:768-828. https://doi.org/10.1016/j.jhep.2023.03.006.

[13] Beran A, Mohamed MFH, Shaear M, et al. Plasma exchange for acute and acute-on-chronic liver failure: a systematic review and meta-analysis. Liver Transpl. 2024;30:127-141. https://doi.org/10.1097/LVT.0000000000000231.

[14] Lv H, Zheng H, Liu J, et al. Expert consensus on liver transplantation periop-erative evaluation and rehabilitation for acute-on-chronic liver failure. Liver Res. 2022;6:121-129. https://doi.org/10.1016/j.livres.2022.08.002.

[15] Bajaj JS, O’Leary JG, Lai JC, et al. Acute-on-chronic liver failure clinical guide-lines. Am J Gastroenterol. 2022;117:225-252. https://doi.org/10.14309/ajg.0000000000001595.

[16] Iloeje UH, Yang HI, Jen CL, et al. Risk and predictors of mortality associated with chronic hepatitis B infection. Clin Gastroenterol Hepatol. 2007;5:921-931. https://doi.org/10.1016/j.cgh.2007.06.015.

[17] Prevention of Mother-To-Child Transmission of Hepatitis B Virus: Guidelines on Antiviral Prophylaxis in Pregnancy. Geneva: World Health Organization; 2020.

[18] Lim SG, Wai CT, Rajnakova A, Kajiji T, Guan R. Fatal hepatitis B reactivation following discontinuation of nucleoside analogues for chronic hepatitis B. Gut. 2002;51:597-599. https://doi.org/10.1136/gut.51.4.597.

[19] Baltrusaitis K, Makanani B, Tierney C, et al. Maternal and infant renal safety following tenofovir disoproxil fumarate exposure during pregnancy in a ran-domized control trial. BMC Infect Dis. 2022;22:634. https://doi.org/10.1186/s12879-022-07608-8.

[20] Chen R, Zou J, Long L, et al. Safety and efficacy of tenofovir alafenamide fumarate in early-middle pregnancy for mothers with chronic hepatitis B. Front Med. 2022;8:796901. https://doi.org/10.3389/fmed.2021.796901.

[21] Hsu HY, Chen HL, Chiang CL, et al. Characterization of hepatitis B virus in tenofovir-treated and untreated chronically infected mothers and their immunoprophylaxis failure infants. Clin Infect Dis. 2023;76:e783ee790. https://doi.org/10.1093/cid/ciac539.

[22] Funk AL, Lu Y, Yoshida K, et al. Efficacy and safety of antiviral prophylaxis during pregnancy to prevent mother-to-child transmission of hepatitis B virus: a systematic review and meta-analysis. Lancet Infect Dis. 2021;21:70-84. https://doi.org/10.1016/S1473-3099(20)30586-7.

[23] Maiwall R, Bajpai M, Choudhury AK, et al. Therapeutic plasma-exchange im-proves systemic inflammation and survival in acute-on-chronic liver failure: a propensity-score matched study from AARC. Liver Int. 2021;41:1083-1096. https://doi.org/10.1111/liv.14806.

[24] Nanchal R, Subramanian R, Alhazzani W, et al. Guidelines for the management of adult acute and acute-on-chronic liver failure in the ICU: neurology, peri-transplant medicine, infectious disease, and gastroenterology considerations. Crit Care Med. 2023;51:657-676. https://doi.org/10.1097/CCM.0000000000005824.

[25] Maiwall R, Bajpai M, Singh A, et al. Standard-volume plasma exchange im-proves outcomes in patients with acute liver failure: a randomized controlled trial. Clin Gastroenterol Hepatol. 2022;20:e831ee854. https://doi.org/10.1016/j.cgh.2021.01.036.

[26] Sadahiro T, Hirasawa H, Oda S, et al. Usefulness of plasma exchange plus continuous hemodiafiltration to reduce adverse effects associated with plasma exchange in patients with acute liver failure. Crit Care Med. 2001;29: 1386-1392. https://doi.org/10.1097/00003246-200107000-00014.

[27] Maiwall R, Rastogi A, Pasupuleti SSR, et al. Natural history, spectrum and outcome of stage 3 AKI in patients with acute-on-chronic liver failure. Liver Int. 2022;42:2800-2814. https://doi.org/10.1111/liv.15413.

[28] Stenbøg P, Busk T, Larsen FS. Efficacy of liver assisting in patients with hepatic encephalopathy with special focus on plasma exchange. Metab Brain Dis. 2013;28:333-335. https://doi.org/10.1007/s11011-013-9403-5.

[29] Cardoso FS, Gottfried M, Tujios S, et al. Continuous renal replacement therapy is associated with reduced serum ammonia levels and mortality in acute liver failure. Hepatology. 2018;67:711-720. https://doi.org/10.1002/hep.29488.