Predictive Value of Inflammatory Cytokines in Early Pregnancy for Liver Dysfunction in Pregnant Women with Hepatitis B

Abstract

The purpose of this study is to explore the predictive value of cytokine levels in the first trimester of pregnancy on abnormal liver function of pregnant women with hepatitis B in the third trimester of pregnancy. A total of 111 pregnant women with HBV infection at 12 weeks gestation participated in the study. The levels of IL-6, IL-8, TNF-α in peripheral blood of the patients and liver function indexes were detected. Subsequently, the pregnant women were followed up, and the liver function was detected at 36 weeks of gestation. According to liver function indexes, patients were divided into normal liver function group and abnormal liver function group to determine the correlation between cytokines in early pregnancy and abnormal liver function in late pregnancy. Kaplan–Meier survival curve and multivariate Cox analysis were used to evaluate the predictive value of cytokines for liver dysfunction. At 12 weeks of gestation, cytokine levels in the normal liver function group were significantly lower than that in the abnormal liver function group. Kaplan–Meier survival analysis showed that the increased IL-6 level was associated with abnormal liver function in late pregnancy. Multivariate Cox regression analysis revealed that IL-6 level was an independent predictor of abnormal liver function in patients with normal liver function in the late pregnancy. The high expression level of cytokine IL-6 at 12 weeks of pregnancy has noteworthy predictive significance for the abnormal liver function of hepatitis B pregnant women in third trimester of pregnancy.

Key words

pregnancy - hepatitis b virus - liver function - cytokines

^‡ These authors contributed equally.

Publication History

Received: 20 June 2022

Accepted after revision: 04 November 2022

Article published online:
29 November 2022

• References

• 1 Zhang F, Wang G.. A review of non-nucleoside anti-hepatitis B virus agents. Eur J Med Chem 2014; 75: 267-281
• 2 Kosinska AD, Zhang E, Lu M. et al. Therapeutic vaccination in chronic hepatitis B: preclinical studies in the woodchuck. Hepat Res Treat 2010; 817580
• 3 Liaw YF.. Rescue therapy for lamivudine-resistant chronic hepatitis B: when and how?. Hepatology 2007; 45: 266-268
• 4 Xu J, Wang J, Xuan S. et al. The effects of childbirth age on maternal and infant outcomes in pregnant women. Iran J Public Health 2018; 47: 788-793
• 5 Li Z, Duan X, Hu Y. et al. Efficacy and safety of lamivudine or telbivudine in preventing mother-to-child transmission of hepatitis B virus: a real-world study. Biomed Res Int 2020; 1374276
• 6 Koeberlein B, zur Hausen A, Bektas N. et al. Hepatitis B virus overexpresses suppressor of cytokine signaling-3 (SOCS3) thereby contributing to severity of inflammation in the liver. Virus Res 2010; 148: 51-59
• 7 Li S, Li H, Xu X. et al. Nanocarrier-mediated antioxidant delivery for liver diseases. Theranostics 2020; 10: 1262-1280
• 8 Han YF, Zhao J, Ma LY. et al. Factors predicting occurrence and prognosis of hepatitis-B-virus-related hepatocellular carcinoma. World J Gastroenterol 2011; 17: 4258-4270
• 9 Ishihara K, Hirano T.. IL-6 in autoimmune disease and chronic inflammatory proliferative disease. Cytokine Growth Factor Rev 2002; 13: 357-368
• 10 Kumar A, Abbas W, Herbein G.. TNF and TNF receptor superfamily members in HIV infection: new cellular targets for therapy?. Mediators Inflamm 2013; 484378
• 11 Qian L, Wang W, Zhou Y. et al. Effects of reduced glutathione therapy on chronic hepatitis B. Cent Eur J Immunol 2017; 42: 97-100
• 12 Lok AS, McMahon BJ.. Chronic hepatitis B: update 2009. Hepatology 2009; 50: 661-662
• 13 Koroleva EP, Fu YX, Tumanov AV.. Lymphotoxin in physiology of lymphoid tissues – Implication for antiviral defense. Cytokine 2018; 101: 39-47
• 14 Yang J.. Development and validation of an online program for promoting self-management among Korean patients with chronic hepatitis B. Nurs Res Pract 2013; 702079
• 15 Lei JH, Liang J, Gong X. et al. Analysis of transmission routes of hepatitis C virus based on virus genotyping in 341 cases with different suspected initial infection time points in Hunan province, China. Med Sci Monit 2018; 24: 5232-5241
• 16 Tocaciu S, Robinson BW, Sambrook PJ.. Severe odontogenic infection in pregnancy: a timely reminder. Aust Dent J 2017; 62: 98-101
• 17 Ewers EC, Pratt WD, Twenhafel NA. et al. Natural history of aerosol exposure with Marburg virus in rhesus macaques. Viruses 2016; 8: 87
• 18 Li M, Sun X, Zhou Z. et al. [Alterations of IFN-gamma and IL-4 of peripheral blood T cells in patients with chronic HBV infection]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2016; 32: 240-244
• 19 Wu HL, Kao JH, Chen TC. et al. Serum cytokine/chemokine profiles in acute exacerbation of chronic hepatitis B: clinical and mechanistic implications. J Gastroenterol Hepatol 2014; 29: 1629-1636
• 20 Kong LZ, Chandimali N, Han YH. et al. Pathogenesis, early diagnosis, and therapeutic management of alcoholic liver disease. Int J Mol Sci 2019; 20: 2712
• 21 Sheron N, Williams R.. IL-8 as a circulating cytokine: induction by recombinant tumour necrosis factor-alpha. Clin Exp Immunol 1992; 89: 100-103
• 22 Shi Q, Shen R, Wang CF. et al. Pretreatment liver injury predicts poor prognosis of DLBCL patients. Mediators Inflamm 2017; 7960907
• 23 McDonald B, Kubes P.. Innate immune cell trafficking and function during sterile inflammation of the liver. Gastroenterology 2016; 151: 1087-1095
• 24 Xiang D, Ren X, Chen Q. et al. Association of ACEI/ARB, inflammatory cytokines, and antiviral drugs with liver dysfunction in patients with hypertension and COVID-19. Clin Exp Hypertens 2021; 43: 305-310
• 25 Flisiak-Jackiewicz M, Bobrus-Chociej A, Tarasow E. et al. Predictive role of interleukin-18 in liver steatosis in obese children. Can J Gastroenterol Hepatol 2018; 3870454
• 26 Steuerwald NM, Foureau DM, Norton HJ. et al. Profiles of serum cytokines in acute drug-induced liver injury and their prognostic significance. PLoS One 2013; 8: e81974
• 27 Sun Y, Gu J, Liu R. et al. IL-2/IL-6 ratio correlates with liver function and recovery in acute liver injury patients. APMIS 2019; 127: 468-474