Variation of Transaminases, HCV-RNA Levels and Th1/Th2 Cytokine Production during the Post-Partum Period in Pregnant Women with Chronic Hepatitis C

This study analyses the evolution of liver disease in women with chronic hepatitis C during the third trimester of pregnancy and the post-partum period, as a natural model of immune modulation and reconstitution. Of the 122 mothers recruited to this study, 89 were HCV-RNA+ve/HIV-ve and 33 were HCV-RNA-ve/HIV-ve/HCVantibody+ve and all were tested during the third trimester of pregnancy, at delivery and post-delivery. The HCV-RNA+ve mothers were categorized as either Type-A (66%), with an increase in ALT levels in the post-partum period (>40 U/L; P<0.001) or as Type-B (34%), with no variation in ALT values. The Type-A mothers also presented a significant decrease in serum HCV-RNA levels in the post-delivery period (P<0.001) and this event was concomitant with an increase in Th1 cytokine levels (INFγ, P = 0.04; IL12, P = 0.01 and IL2, P = 0.01). On the other hand, the Type-B mothers and the HCV-RNA-ve women presented no variations in either of these parameters. However, they did present higher Th1 cytokine levels in the partum period (INFγ and IL2, P<0.05) than both the Type-A and the HCV-RNA-ve women. Cytokine levels at the moment of delivery do not constitute a risk factor associated with HCV vertical transmission. It is concluded that differences in the ALT and HCV-RNA values observed in HCV-RNA+ve women in the postpartum period might be due to different ratios of Th1 cytokine production. In the Type-B women, the high partum levels of Th1 cytokines and the absence of post-partum variation in ALT and HCV-RNA levels may be related to permanent Th1 cytokine stimulation.

本研究以免疫调节与重建的自然模型为依托，分析妊娠晚期及产后慢性丙型肝炎（chronic hepatitis C）女性患者的肝脏疾病演化进程。本研究共招募122名产妇，其中89名为丙型肝炎病毒核糖核酸（HCV-RNA）阳性/人类免疫缺陷病毒（HIV）阴性者，33名为丙型肝炎病毒核糖核酸阴性/人类免疫缺陷病毒阴性/丙型肝炎病毒抗体阳性者；所有受试者均在妊娠晚期、分娩时及产后接受检测。
丙型肝炎病毒核糖核酸阳性产妇可分为A型（占比66%）与B型（占比34%）：A型产妇产后丙氨酸氨基转移酶（ALT）水平升高（>40 U/L；P<0.001），而B型产妇丙氨酸氨基转移酶水平无明显变化。A型产妇在产后血清丙型肝炎病毒核糖核酸水平亦显著降低（P<0.001），该变化与Th1型细胞因子（Th1 cytokine）水平升高同步发生（干扰素γ（INFγ），P=0.04；白细胞介素12（IL12），P=0.01；白细胞介素2（IL2），P=0.01）。
与之相反，B型产妇及丙型肝炎病毒核糖核酸阴性受试者的上述指标均无明显变化。然而，分娩时该两组受试者的Th1型细胞因子水平（干扰素γ与白细胞介素2，P<0.05）均高于A型产妇及丙型肝炎病毒核糖核酸阴性受试者。分娩时的细胞因子水平并非与HCV垂直传播相关的危险因素。
研究结论认为，产后丙型肝炎病毒核糖核酸阳性产妇所观察到的丙氨酸氨基转移酶与丙型肝炎病毒核糖核酸水平差异，可能源于Th1型细胞因子产生比例的不同。对于B型产妇而言，分娩时较高的Th1型细胞因子水平，以及产后丙氨酸氨基转移酶与丙型肝炎病毒核糖核酸水平无明显变化的特征，可能与持续性Th1型细胞因子刺激相关。