Effect of non-alcoholic fatty liver disease on pregnancy outcomes and antiviral therapy in pregnant women with hepatitis B: a retrospective cohort study

doi:10.19871/j.cnki.xfcrbzz.2022.02.012

Abstract

Abstract: Objective To study the effects of non-alcoholic fatty liver disease (NAFLD) on pregnancy outcome and the antiviral treatment during pregnancy of women with hepatitis B, so as to provide more reliable evidence for improving the management of pregnancy and perinatal period in this population. Method Pregnant women with hepatitis B who delivered in the Second Hospital of Nanjing from January 1, 2020 to December 31, 2021 were selected and divided into NAFLD group(35 cases) and non-NAFLD group(156 cases) according to whether NAFLD was present or not. Matches were made by propensity score matching. The statistical analysis of pregnancy outcomes（25 pairs of patients） and antiviral treatment effect（12 pairs of patients） were performed between the two groups. Result Compared with non-NAFLD group, NAFLD group had an increased risk of adverse maternal and off spring outcomes (both P<0.05). And there was statistically significant difference in the scores of adverse maternal and offspring outcomes between the two groups (P=0.01). It was found that platelet count in NAFLD group was higher than non-NAFLD group at different stage of gestation and postpartum 42 days, while mean platelet volume was lower than control group. There were no statistically significant differences in HBV DNA levels at baseline, 4 and 8 weeks of antiviral therapy between the two groups of pregnant women with high viral load who initiated antiviral therapy in the second trimester of pregnancy. Conclusion NAFLD increased the risk of maternal and fetal adverse outcomes in pregnant women with hepatitis B, but had no significant effect on antiviral therapy initiating in the second trimester of pregnancy in women with high viral load. The platelet-related indicators may be potential prognostic predictors of pregnant women with hepatitis B combined NAFLD.

Key words: Non-alcoholic fatty liver disease, Pregnant women with hepatitis B, Pregnancy outcomes, Antiviral therapy

Wang Chenxu, Li li, Han Guorong, Yuan Deping, Ye Xiajun. Effect of non-alcoholic fatty liver disease on pregnancy outcomes and antiviral therapy in pregnant women with hepatitis B: a retrospective cohort study[J]. Electronic Journal of Emerging Infectious Diseases, 2022, 7(2): 57-62.

References

[1] YOUNOSSI Z, ANSTEE QM, MARIETTI M, et al.Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention[J]. Nat Rev Gastroenterol Hepatol, 2018, 15(1):11-20.
[2] ZHOU J, ZHOU F, WANG W, et al.Epidemiological Features of NAFLD From 1999 to 2018 in China[J]. Hepatology, 2020, 71(5):1851-1864.
[3] FORBES S, TAYLOR-ROBINSON SD, PATEL N, et al.Increased prevalence of non-alcoholic fatty liver disease in European women with a history of gestational diabetes[J]. Diabetologia, 2011, 54(3):641-647.
[4] SARKAR M, GRAB J, DODGE JL, et al.Non-alcoholic fatty liver disease in pregnancy is associated with adverse maternal and perinatal outcomes[J]. J Hepatol, 2020, 73(3):516-522.
[5] 易永祥. 乙型肝炎病毒的分子流行病学研究进展[J/CD]. 新发传染病电子杂志, 2020, 5(1):1-7.
[6] Cui F, Woodring J, Chan P, et al.Considerations of antiviral treatment to interrupt mother-to-child transmission of hepatitis B virus in China[J].Int J Epidemiol, 2018, 47(5):1529-1537.
[7] MACHADO MV, OLIVEIRA AG, CORTEZ-PINTO H.Hepatic steatosis in hepatitis B virus infected patients: meta-analysis of risk factors and comparison with hepatitis C infected patients[J]. J Gastroenterol Hepatol, 2011, 26(9):1361-1367.
[8] LIANG J, CAI W, HAN T, et al.The expression of thymosin β4 in chronic hepatitis B combined nonalcoholic fatty liver disease[J]. Medicine (Baltimore), 2016, 95(52):e5763.
[9] WANG MM, WANG GS, SHEN F, et al.Hepatic steatosis is highly prevalent in hepatitis B patients and negatively associated with virological factors[J]. Dig Dis Sci, 2014, 59(10):2571-2579.
[10] UNAL C, TANACAN A, ZIYADOVA G, et al.Effect of viral load on pregnancy outcomes in chronic hepatitis B infection[J]. J Obstet Gynaecol Res, 2019, 45(9):1837-1842.
[11] CUI AM, CHENG XY, SHAO JG, et al.Maternal hepatitis B virus carrier status and pregnancy outcomes: a prospective cohort study[J]. BMC Pregnancy Child birth, 2016, 16:87.
[12] Safir A, Levy A, Sikuler E, et al.Maternal hepatitis B virus or hepatitis C virus carrier status as an independent risk factor for adverse perinatal outcome[J].Liver Int, 2010, 30(5):765-770.
[13] SALEMI JL, WHITEMAN VE, AUGUST EM, et al.Maternal hepatitis B and hepatitis C infection and neonatal neurological outcomes[J]. J Viral Hepat, 2014, 21(11): 144-153.
[14] TAN J, MAO X, ZHANG G, et al.Hepatitis B surface antigen positivity during pregnancy and risk of gestational diabetes mellitus: A systematic review and meta-analysis[J]. J Viral Hepat, 2018, 25(11):1372-1383.
[15] TAN J, LIU X, MAO X, et al.HBsAg positivity during pregnancy and adverse maternal outcomes: a retrospective cohort analysis[J]. J Viral Hepat, 2016, 23(10):812-819.
[16] HAGSTRöM H, HöIJER J, LUDVIGSSON JF, et al. Adverse outcomes of pregnancy in women with non-alcoholic fatty liver disease[J]. Liver Int, 2016, 36(2):268-274.
[17] LEE SM, KIM BJ, KOO JN, et al.Nonalcoholic fatty liver disease is a risk factor for large-for-gestational-age birthweight[J]. PLoS One, 2019, 14(8):e0221400.
[18] LEE SM, JUNG YM, CHOI ES, et al.Metabolic Dysfunction-Associated Fatty Liver Disease and Subsequent Development of Adverse Pregnancy Outcomes[J]. Clin Gastroenterol Hepatol, 2021, 3565(21):1219-1222
[19] JIN X, CHEN Y P, YANG Y D, et al.Association between hepatic steatosis and entecavir treatment failure in Chinese patients with chronic hepatitis B[J]. PLoS One, 2012, 7(3):e34198.
[20] ZHU Y, YANG Q, LV F, et al.The Effect of Hepatosteatosis on Response to Antiviral Treatment in Patients with Chronic Hepatitis B: A Meta-Analysis[J]. Gastroenterol Res Pract, 2017, 2017:1096406.
[21] 中国肝炎防治基金会, 中华医学会感染病学分会, 中华医学会肝病学分会.阻断乙型肝炎病毒母婴传播临床管理流程(2021年)[J]. 中华肝脏病杂志, 2021, 29(4):313-318.
[22] SIVAN E, HOMKO CJ, CHEN X, et al.Effect of insulin on fat metabolism during and after normal pregnancy[J]. Diabetes, 1999, 48(4):834-838.
[23] LEE SM, KWAK SH, KOO JN, et al.Non-alcoholic fatty liver disease in the first trimester and subsequent development of gestational diabetes mellitus[J]. Diabetologia, 2019, 62(2):238-248.
[24] YIN W, CHEN B, YANG Y, et al.Association between maternal hepatitis B virus carrier and gestational diabetes mellitus: a retrospective cohort analysis[J]. Virol J, 2021, 18(1):226.
[25] LOPEZ-JARAMILLO P, BARAJAS J, RUEDA-QUIJANO SM, et al.Obesity and Preeclampsia: Common Pathophysiological Mechanisms[J]. Front Physiol, 2018, 9:1838.
[26] YKI-JäRVINEN H. Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome[J]. Lancet Dia Endocr, 2014, 2(11):901-910.
[27] 谢幸, 孔北华, 段涛.妇产科学[M].9版.北京:人民卫生出版社, 2018:43.
[28] CNATTINGIUS S, VILLAMOR E, JOHANSSON S, et al.Maternal obesity and risk of preterm delivery[J]. JAMA, 2013, 309(22):2362-2370.
[29] METZGER BE, LOWE LP, DYER AR, et al.Hyperglycemia and adverse pregnancy outcomes[J]. N Engl J Med, 2008, 358(19):1991-2002.
[30] MITANCHEZ D.Foetal and neonatal complications in gestational diabetes: perinatal mortality, congenital malformations, macrosomia, shoulder dystocia, birth injuries, neonatal complications[J]. Diabetes Metab, 2010, 36(6 Pt 2):617-627.
[31] MICHALAK A, CICHO-LACH H, GUZ M, et al.Plateletcrit and Mean Platelet Volume in the Evaluation of Alcoholic Liver Cirrhosis and Nonalcoholic Fatty Liver Disease Patients[J]. Biomed Res Int, 2021, 2021:8867985.
[32] GARRAUD O, COGNASSE F.Are Platelets Cells? And if Yes, are They Immune Cells?[J]. Front Immunol, 2015, 6:70.
[33] SUTTI S, ALBANO E.Adaptive immunity: an emerging player in the progression of NAFLD[J]. Nat Rev Gastroenterol Hepatol, 2020, 17(2):81-92.
[34] TILG H, ADOLPH TE, DUDEK M, et al.Non-alcoholic fatty liver disease: the interplay between metabolism, microbes and immunity[J]. Nat Metab, 2021, 3(12):1596-1607.
[35] SHAO L N, ZHANG S T, WANG N, et al.Platelet indices significantly correlate with liver fibrosis in HCV-infected patients[J]. PLoS One, 2020, 15(1):e0227544.
[36] KANEDA H, HASHIMOTO E, YATSUJI S, et al.Hyaluronic acid levels can predict severe fibrosis and platelet counts can predict cirrhosis in patients with nonalcoholic fatty liver disease[J]. J Gastroenterol Hepatol, 2006, 21(9):1459-1465.
[37] POKORA RA, KICIAK S, TOMASIEWICZ K.Neutrophil-lymphocyte ratio and mean platelet volume as predictive factors for liver fibrosis and steatosis in patients with chronic hepatitis B[J]. Ann Agric Environ Med, 2018, 25(4):690-692.
[38] HERNAEZ R,LAZO M,BONEKAMP S, et al.Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis[J].Hepatology, 2011, 54(3):1082-1090.
[39] BRIL F, ORTIZ-LOPEZ C, LOMONACO R, et al.Clinical value of liver ultrasound for the diagnosis of nonalcoholic fatty liver disease in overweight and obese patients[J]. Liver Int, 2015, 35(9):2139-2146.
[40] LONG MT, GURARY EB, MASSARO JM, et al.Parental non-alcoholic fatty liver disease increases risk of non-alcoholic fatty liver disease in offspring[J]. Liver Int, 2019, 39(4):740-747.
[41] QUERTER I, PAUWELS NS, DE BRUYNE R, et al.Maternal and Perinatal Risk Factors for Pediatric Nonalcoholic Fatty Liver Disease: A Systematic Review[J]. Clin Gastroenterol Hepatol, 2021, 20(4):740-755.