Department of Medicine, LNJP Hospital, MAMC, New Delhi, India.
J Hepatol. 2011 Jun;54(6):1107-13. doi: 10.1016/j.jhep.2010.08.037. Epub 2010 Nov 13.
BACKGROUND & AIMS: Hepatitis E virus (HEV) infection is associated with high maternal and fetal mortalities. A prospective study was undertaken to evaluate the role of viral and host factors in HEV related pregnancy outcomes.
The study included HEV infected pregnancy cases; acute viral hepatitis (AVH), n=100 and fulminant hepatic failure (FHF), n=43, and healthy pregnancy cases, n=50. HEV genotypes and viremia were studied by nucleotide sequencing and real time PCR, respectively. Progesterone receptor (PR) gene mutations (PROGINS) were studied by PCR, PR expression at the mRNA and protein levels in the placenta were studied by semi-quantitative RT-PCR and immunohistochemistry, respectively. Progesterone induced blocking factor (PIBF) expression was studied by RT-PCR in blood. Serum interleukin-10 (IL-10) and interleukin-12 (IL-12) levels were assayed by ELISA.
HEV viral load was significantly higher in FHF than AVH (p<0.001) and in cases with fetal mortality in AVH (p=0.001) and FHF (p=0.018). PROGINS were predominant in FHF compared to AVH (p=0.26) and showed reduced mRNA and protein expression. The risk of fetal mortality in AVH was two times higher (OR, 2.190; CI, 0.303-15.85) and maternal and fetal mortalities in FHF were 4-fold (OR, 4.0; CI, 0.363-44.113) increased in PROGINS carriers. PR and PIBF expression was lower in AVH and even lower in FHF compared to healthy controls. The higher IL-12/IL-10 ratio observed in FHF compared to other groups correlated with fetal mortality in AVH and FHF (p<0.001).
In conclusion, reduced expression of PR and PIBF, a higher IL-12/IL-10 ratio, and a high viral load results in poor pregnancy outcome in Hepatitis E.
戊型肝炎病毒（HEV）感染与高孕产妇和胎儿死亡率相关。本研究旨在评估病毒和宿主因素在戊型肝炎病毒相关妊娠结局中的作用。
研究纳入了 HEV 感染的妊娠病例、急性病毒性肝炎（AVH）100 例、肝衰竭（FHF）43 例和健康妊娠病例 50 例。通过核苷酸测序和实时 PCR 分别研究 HEV 基因型和病毒血症。通过 PCR 研究孕激素受体（PR）基因突变（PROGINS），通过半定量 RT-PCR 和免疫组化分别研究胎盘 PR 表达的 mRNA 和蛋白水平，通过 RT-PCR 在血液中研究孕激素诱导阻断因子（PIBF）的表达。通过 ELISA 测定血清白细胞介素-10（IL-10）和白细胞介素-12（IL-12）水平。
FHF 患者的 HEV 病毒载量明显高于 AVH（p<0.001），且在 AVH（p=0.001）和 FHF（p=0.018）中胎儿死亡的病例中病毒载量更高。与 AVH 相比，FHF 中 PROGINS 更为常见（p=0.26），且 mRNA 和蛋白表达降低。AVH 中胎儿死亡的风险增加了两倍（OR，2.190；CI，0.303-15.85），FHF 中母婴死亡率增加了 4 倍（OR，4.0；CI，0.363-44.113），在 PROGINS 携带者中更为常见。与健康对照组相比，AVH 和 FHF 中 PR 和 PIBF 的表达水平较低。与其他组相比，FHF 中观察到的较高的 IL-12/IL-10 比值与 AVH 和 FHF 中的胎儿死亡相关（p<0.001）。
总之，PR 和 PIBF 表达降低、IL-12/IL-10 比值升高、病毒载量升高导致戊型肝炎妊娠结局不良。
