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

Ángeles Ruiz-Extremera,Julián López Viota,Ana Belén Martín,Javier Salmerón,Ángel Carazo,Esther Ocete-Hita,Paloma Muñoz-De-Rueda,Sergio Manuel Jimenez-Ruiz,Ana Abril-Molina,María Angustias Salmerón-Ruiz,Laura Sanjuán-Núñez,Josefa León,Jorge Casado,Esther José Pavón-Castillero,Rosa Quiles-Pérez,Ana Gila,José Antonio Muñoz-Gámez

doi:10.1371/journal.pone.0075613

Abstract

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.

Highlights

Infection with hepatitis C virus (HCV) is a worldwide health problem, affecting over 170 million persons, and is the most common cause of cirrhosis, hepatocellular carcinoma and liver transplantation [1,2]
HCV affects a significant number of pregnant women, few studies have examined the role of chronic HCV infection on pregnancy outcomes, and the results presented are contradictory
These data suggest that the reduced hepatic damage detected in chronic HCV pregnant women may be mediated by a modified T helper 1 (Th1) immune response during pregnancy [8]; it should be noted that very few data have been reported and that many unanswered questions remain in this respect

Summary

Introduction

Infection with hepatitis C virus (HCV) is a worldwide health problem, affecting over 170 million persons, and is the most common cause of cirrhosis, hepatocellular carcinoma and liver transplantation [1,2]. The natural history of chronic HCV infection during pregnancy and the puerperium has not been clearly established In this period, the maternal immune system must develop a tolerance to paternal alloantigens in order to prevent maternal immune aggressions against the foetus and maintain active immunity against infectious agents to protect both the mother and foetus [20] For this reason, during pregnancy, the T helper 1 (Th1) associated cellular immune response is repressed and Th2-type immunity is stimulated in response to pathogens [21,22]. These data suggest that the reduced hepatic damage detected in chronic HCV pregnant women (measured as low ALT levels) may be mediated by a modified Th1 immune response during pregnancy [8]; it should be noted that very few data have been reported and that many unanswered questions remain in this respect

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