Saxena Anoushka, Pahwa Prabhjyoti, Maras Jaswinder Singh, Siddiqui Hamda, Sevak Jayesh Kumar, Mala Yedla Manikya, Tyagi Shakun, Sarin Shiv K, Trehanpati Nirupama
Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
Department of Obstetrics and Gynaecology, Maulana Azad Medical College, New Delhi, India.
Hepatol Commun. 2025 Feb 3;9(2). doi: 10.1097/HC9.0000000000000608. eCollection 2025 Feb 1.
Hepatitis-E virus (HEV)-induced liver failure during pregnancy leads to maternal and fetal complications. This study investigates the HEV-associated metabolomic and immunological changes to elucidate the worsening of obstetric outcomes in patients with acute liver failure (ALF) due to HEV.
Pregnant women with (i) acute viral hepatitis, IgM HEV positive (AVH-E, n = 31, Gr.I), (ii) acute liver failure (ALF-E, n = 15, Gr.II), (iii) acute hepatitis but negative for viral infections (non-HEV, n = 30, Gr.III), and healthy (HC, n = 21, Gr.IV) were evaluated at delivery for plasma untargeted metabolomics, cytokine, and immune profiling.
AVH-E and ALF-E (Gr.I, II) showed elevated TNF-α, IL-1β, IL-9, IL-22, and IL-33 compared to HC. In addition, in ALF-E, IFN-γ and IL-12p70 were decreased, but MIP-1α, fractalkine, SDF-1α, IL-22, and IL-33 were increased compared to AVH-E. Both AVH-E and ALF-E had decreased choline, sn-glycero-3-phosphocholine, O-palmitoyl-r-carnitine, and increased taurocholic acid. However, patients with ALF-E had a 2-5-fold decline in these metabolites with raised taurochenodeoxycholic acid. ALF-E showed increased naive T/B cells, decreased CD4, CD8 Tcm, Tem, and plasmablasts, compared to AVH-E contributing to higher failed inductions, preterm births, maternal complications like eclampsia, disseminated intravascular coagulation, preterm premature rupture of membranes, small-for-gestational-age infants, higher rates of intrauterine death, abortion, and mortality.
HEV infection reduces choline, phosphocholine, and palmitoyl carnitine, enhancing inflammation in ALF-E, while increasing taurocholic and taurochenodeoxycholic acids impairs the immune response. These factors together likely contribute to severe obstetric complications, including higher failed inductions, intrauterine death, and maternal and fetal mortality in ALF-E.
戊型肝炎病毒（HEV）感染导致的妊娠期肝衰竭会引发母婴并发症。本研究旨在调查与HEV相关的代谢组学和免疫学变化，以阐明戊型肝炎所致急性肝衰竭（ALF）患者产科结局恶化的原因。
对分娩时的孕妇进行评估，包括（i）急性病毒性肝炎且IgM HEV阳性（AVH-E，n = 31，I组），（ii）急性肝衰竭（ALF-E，n = 15，II组），（iii）急性肝炎但病毒感染阴性（非HEV，n = 30，III组），以及健康孕妇（HC，n = 21，IV组），检测血浆非靶向代谢组学、细胞因子和免疫谱。
与HC组相比，AVH-E组和ALF-E组（I组、II组）的TNF-α、IL-1β、IL-9、IL-22和IL-33升高。此外，与AVH-E组相比，ALF-E组中IFN-γ和IL-12p70降低，但MIP-1α、趋化因子、SDF-1α、IL-22和IL-33升高。AVH-E组和ALF-E组的胆碱、sn-甘油-3-磷酸胆碱、O-棕榈酰-r-肉碱均降低，牛磺胆酸升高。然而，ALF-E组这些代谢物下降了2至5倍，而牛磺鹅去氧胆酸升高。与AVH-E组相比，ALF-E组的初始T/B细胞增加，CD4、CD8 Tcm、Tem和浆母细胞减少，导致引产失败、早产、子痫、弥散性血管内凝血、胎膜早破、小于胎龄儿、宫内死亡、流产和死亡率增加。
HEV感染会降低胆碱、磷酸胆碱和棕榈酰肉碱水平，增强ALF-E组的炎症反应，而牛磺胆酸和牛磺鹅去氧胆酸增加会损害免疫反应。这些因素共同导致了严重的产科并发症，包括ALF-E组引产失败、宫内死亡以及母婴死亡率增加。
