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Variation of transaminases, HCV-RNA levels and Th1/Th2 cytokine production during the post-partum period in pregnant women with chronic hepatitis C.

Ruiz-Extremera A, Muñoz-Gámez JA, Abril-Molina A, Salmerón-Ruiz MA, Muñoz-de-Rueda P, Pavón-Castillero EJ, Quiles-Pérez R, Carazo A, Gila A, Jimenez-Ruiz SM, Casado J, Martín AB, Sanjuán-Núñez L, Ocete-Hita E, Viota JL, León J, Salmerón J - PLoS ONE (2013)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Paediatric Unit, San Cecilio University Hospital, Granada, Spain ; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Ciberehd, Granada, Spain ; Paediatric Unit, Granada University, Granada, Spain.

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.

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Relation between ALT levels and HCV viral load in the serum of Type-A and Type-B mothers.Statistical analysis was performed using the paired/unpaired Student's t test for normally distributed quantitative variables and the Mann-Whitney Test for quantitative variables with a non-normal distribution. The Kolmogorov-Smirnov test was used to analyse the distribution of quantitative variables. *, § P<0.001, comparing the third trimester of pregnancy, delivery and 7–12 months post-partum.
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pone-0075613-g002: Relation between ALT levels and HCV viral load in the serum of Type-A and Type-B mothers.Statistical analysis was performed using the paired/unpaired Student's t test for normally distributed quantitative variables and the Mann-Whitney Test for quantitative variables with a non-normal distribution. The Kolmogorov-Smirnov test was used to analyse the distribution of quantitative variables. *, § P<0.001, comparing the third trimester of pregnancy, delivery and 7–12 months post-partum.

Mentions: Analysis of ALT and HCV viral load revealed a temporal correlation among the Type-A mothers (Figure 2); ALT levels had increased and the viral load had decreased at 3–6 months post-partum (Figure S1; P<0.0001; Pearson's R = −0.740). However, the Type-B women did not present this correlation (Figure S1; P = 0.234; Pearson's R = 0.234) Furthermore, analysis of the HCV viral load in the Type-A women (Figure S2) showed that both in the mothers with high HCV-RNA viral load (>600,000 IU/mL) and in those with low HCV-RNA levels at delivery (≤600,000 IU/mL), there was a significant decrease in the HCV viral load. This post-partum decrease was independent of the HCV-RNA values at delivery. However, the Type-A women, whether with high or low viral load at delivery, presented raised INFγ, IL12 and IL2 levels post-partum (compared with the partum values, Th1 cytokines, Figure S3) and higher levels of IL10 (Th2 and anti-inflammatory cytokines). These data suggest that the cytokine behaviour pattern has a stronger influence on ALT evolution at delivery and 3–6 months post-partum than does the viral load at the same times. On the other hand, the Type-B women classified according to viral load at delivery did not present this behaviour pattern with respect to the evolution of cytokine levels in the peripheral blood.


Variation of transaminases, HCV-RNA levels and Th1/Th2 cytokine production during the post-partum period in pregnant women with chronic hepatitis C.

Ruiz-Extremera A, Muñoz-Gámez JA, Abril-Molina A, Salmerón-Ruiz MA, Muñoz-de-Rueda P, Pavón-Castillero EJ, Quiles-Pérez R, Carazo A, Gila A, Jimenez-Ruiz SM, Casado J, Martín AB, Sanjuán-Núñez L, Ocete-Hita E, Viota JL, León J, Salmerón J - PLoS ONE (2013)

Relation between ALT levels and HCV viral load in the serum of Type-A and Type-B mothers.Statistical analysis was performed using the paired/unpaired Student's t test for normally distributed quantitative variables and the Mann-Whitney Test for quantitative variables with a non-normal distribution. The Kolmogorov-Smirnov test was used to analyse the distribution of quantitative variables. *, § P<0.001, comparing the third trimester of pregnancy, delivery and 7–12 months post-partum.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3794969&req=5

pone-0075613-g002: Relation between ALT levels and HCV viral load in the serum of Type-A and Type-B mothers.Statistical analysis was performed using the paired/unpaired Student's t test for normally distributed quantitative variables and the Mann-Whitney Test for quantitative variables with a non-normal distribution. The Kolmogorov-Smirnov test was used to analyse the distribution of quantitative variables. *, § P<0.001, comparing the third trimester of pregnancy, delivery and 7–12 months post-partum.
Mentions: Analysis of ALT and HCV viral load revealed a temporal correlation among the Type-A mothers (Figure 2); ALT levels had increased and the viral load had decreased at 3–6 months post-partum (Figure S1; P<0.0001; Pearson's R = −0.740). However, the Type-B women did not present this correlation (Figure S1; P = 0.234; Pearson's R = 0.234) Furthermore, analysis of the HCV viral load in the Type-A women (Figure S2) showed that both in the mothers with high HCV-RNA viral load (>600,000 IU/mL) and in those with low HCV-RNA levels at delivery (≤600,000 IU/mL), there was a significant decrease in the HCV viral load. This post-partum decrease was independent of the HCV-RNA values at delivery. However, the Type-A women, whether with high or low viral load at delivery, presented raised INFγ, IL12 and IL2 levels post-partum (compared with the partum values, Th1 cytokines, Figure S3) and higher levels of IL10 (Th2 and anti-inflammatory cytokines). These data suggest that the cytokine behaviour pattern has a stronger influence on ALT evolution at delivery and 3–6 months post-partum than does the viral load at the same times. On the other hand, the Type-B women classified according to viral load at delivery did not present this behaviour pattern with respect to the evolution of cytokine levels in the peripheral blood.

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Paediatric Unit, San Cecilio University Hospital, Granada, Spain ; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Ciberehd, Granada, Spain ; Paediatric Unit, Granada University, Granada, Spain.

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.

Show MeSH
Related in: MedlinePlus