Limits...
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.

Show MeSH

Related in: MedlinePlus

Evolution of ALT (A) and cytokine serum levels (B) in HCV-RNA-ve and HCV-RNA+ve pregnant women (categorized into 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<0.01 comparing HCV-RNA+ve and HCV-RNA-ve mothers. §§P<0.01 comparing HCV-RNA+ve mothers, 3–6 months post-partum, at delivery and at 7–12 months post-delivery.*P<0.01 comparing Type-A and Type-B HCV-RNA+ve mothers. **P<0.001 comparing Type-A mothers at 3-6 months post-partum, at delivery and at 7–12 months post-partum.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3794969&req=5

pone-0075613-g001: Evolution of ALT (A) and cytokine serum levels (B) in HCV-RNA-ve and HCV-RNA+ve pregnant women (categorized into 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<0.01 comparing HCV-RNA+ve and HCV-RNA-ve mothers. §§P<0.01 comparing HCV-RNA+ve mothers, 3–6 months post-partum, at delivery and at 7–12 months post-delivery.*P<0.01 comparing Type-A and Type-B HCV-RNA+ve mothers. **P<0.001 comparing Type-A mothers at 3-6 months post-partum, at delivery and at 7–12 months post-partum.

Mentions: The evolution of ALT in the HCV-RNA+ve and in the HCV-RNA-ve women is shown in Figure 1A. Interestingly, non-significant differences in ALT values were observed between these groups during the third trimester of pregnancy (from week 28 of gestation to the end of the pregnancy), and at delivery. However, after delivery (3–6 months post-partum), the HCV-RNA+ve mothers showed higher ALT levels than did the HCV-RNA-ve mothers (98.32±9.34 U/L vs. 17.42±1.77 U/L; P<0.001). Moreover, the HCV-RNA+ve mothers presented a significant increase in Th1 cytokines at 3–6 months post-partum (ΔINFγ = INFγpost-partum–INFγpartum = 9.1±2.5ρg/mL, P = 0.03; ΔIL12 = IL12post-partum–IL12partum = 0.85±0.30ρg/mL, P = 0.01 and ΔIL2 = IL2post-partum–IL2partum = 5.4±2.89ρg/mL, P = 0.07) whereas in the HCV-RNA-ve mothers the cytokine values in the peripheral blood remained unchanged (however this does not mean that such differences do not exist in the placenta, decidua and umbilical cord). Furthermore, the HCV-RNA+ve mothers had higher cytokine levels than the HCV-RNA-ve mothers, both at delivery and 3–6 months post-partum. On the other hand, in the HCV-RNA+ve mothers there was no significant association between cytokine levels and IL28B polymorphism (CC vs non-CC) or between cytokine levels and viral genotype [geno. 1 (1a vs 1b) and vs geno. non-1 (3 and 4)].


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)

Evolution of ALT (A) and cytokine serum levels (B) in HCV-RNA-ve and HCV-RNA+ve pregnant women (categorized into 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<0.01 comparing HCV-RNA+ve and HCV-RNA-ve mothers. §§P<0.01 comparing HCV-RNA+ve mothers, 3–6 months post-partum, at delivery and at 7–12 months post-delivery.*P<0.01 comparing Type-A and Type-B HCV-RNA+ve mothers. **P<0.001 comparing Type-A mothers at 3-6 months post-partum, at delivery and at 7–12 months post-partum.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3794969&req=5

pone-0075613-g001: Evolution of ALT (A) and cytokine serum levels (B) in HCV-RNA-ve and HCV-RNA+ve pregnant women (categorized into 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<0.01 comparing HCV-RNA+ve and HCV-RNA-ve mothers. §§P<0.01 comparing HCV-RNA+ve mothers, 3–6 months post-partum, at delivery and at 7–12 months post-delivery.*P<0.01 comparing Type-A and Type-B HCV-RNA+ve mothers. **P<0.001 comparing Type-A mothers at 3-6 months post-partum, at delivery and at 7–12 months post-partum.
Mentions: The evolution of ALT in the HCV-RNA+ve and in the HCV-RNA-ve women is shown in Figure 1A. Interestingly, non-significant differences in ALT values were observed between these groups during the third trimester of pregnancy (from week 28 of gestation to the end of the pregnancy), and at delivery. However, after delivery (3–6 months post-partum), the HCV-RNA+ve mothers showed higher ALT levels than did the HCV-RNA-ve mothers (98.32±9.34 U/L vs. 17.42±1.77 U/L; P<0.001). Moreover, the HCV-RNA+ve mothers presented a significant increase in Th1 cytokines at 3–6 months post-partum (ΔINFγ = INFγpost-partum–INFγpartum = 9.1±2.5ρg/mL, P = 0.03; ΔIL12 = IL12post-partum–IL12partum = 0.85±0.30ρg/mL, P = 0.01 and ΔIL2 = IL2post-partum–IL2partum = 5.4±2.89ρg/mL, P = 0.07) whereas in the HCV-RNA-ve mothers the cytokine values in the peripheral blood remained unchanged (however this does not mean that such differences do not exist in the placenta, decidua and umbilical cord). Furthermore, the HCV-RNA+ve mothers had higher cytokine levels than the HCV-RNA-ve mothers, both at delivery and 3–6 months post-partum. On the other hand, in the HCV-RNA+ve mothers there was no significant association between cytokine levels and IL28B polymorphism (CC vs non-CC) or between cytokine levels and viral genotype [geno. 1 (1a vs 1b) and vs geno. non-1 (3 and 4)].

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