RESUMO
INTRODUCTION AND OBJECTIVES: Intrahepatic cholestasis of pregnancy (ICP) is often accompanied by fetal and maternal complications. MATERIALS AND METHODS: Retrospective review of the clinical course of women with ICP and their neonates treated at our medical center over a 10-year period. Special attention was paid to the maternal and neonatal response to 2 different modes of ursodeoxycholic acid (UDCA) administration. RESULTS: Neonates of mothers with high total bile acid levels had a poorer composite neonatal outcome. Twenty-seven women who presented at an advanced stage of their pregnancies did not receive UDCA. UDCA was administered in 2 modes: either a full dose at admission (76 women) or a gradually increasing dose until the desired dosage was reached (25 women). The mean gestational age at delivery for the 94 neonates that were exposed to full UDCA dose was the lowest (36±2.3 weeks for the full dose, 37±1.4 weeks for the 30 neonates from the gradually increasing dose, 38±1.6 weeks for the 29 neonates from the no treatment group, p<0.001). The group of neonates that were exposed to full UDCA dose had the highest rate of unfavorable composite neonatal outcome (53% for full dose, 30% for gradually increasing dose, 24% for the no treatment group, p=0.006). CONCLUSIONS: Compared to the administration of a full UDCA dose, the administration of a gradually increasing dose of UDCA may be associated with a greater gestational age at delivery and fewer events of unfavorable composite neonatal outcomes. These novel findings should be retested prospectively in a large cohort of patients.
Assuntos
Colagogos e Coleréticos , Colestase Intra-Hepática , Idade Gestacional , Complicações na Gravidez , Ácido Ursodesoxicólico , Humanos , Ácido Ursodesoxicólico/administração & dosagem , Ácido Ursodesoxicólico/uso terapêutico , Feminino , Gravidez , Colestase Intra-Hepática/tratamento farmacológico , Colestase Intra-Hepática/diagnóstico , Colestase Intra-Hepática/sangue , Estudos Retrospectivos , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/sangue , Recém-Nascido , Colagogos e Coleréticos/administração & dosagem , Colagogos e Coleréticos/efeitos adversos , Colagogos e Coleréticos/uso terapêutico , Adulto , Resultado do Tratamento , Resultado da GravidezRESUMO
INTRODUCTION AND OBJECTIVES: Intrahepatic cholestasis is a frequent disease during pregnancy. It is unknown if liver function alterations produce specific placental lesions. The aim of this study was to evaluate placental histopathological changes in patients with intrahepatic cholestasis of pregnancy (ICP), and to explore correlations between the placental histopathology and hepatic function alteration or patient comorbidities, and body mass index. PATIENTS AND METHODS: A retrospective cohort study included women with ICP, most of them showing comorbidities such as overweight/obesity, preeclampsia and gestational diabetes. They were attended at the National Institute of Perinatology in Mexico City for three years. Placental histopathological alterations were evaluated according to the Amsterdam Placental Workshop Group Consensus Statement. Data was analyzed using Graph-Pad Prism 5. RESULTS: The results indicated that the placenta of ICP patients showed many histopathological alterations; however, no correlations were observed between the increase in bile acids or liver functional parameters and specific placental lesions. The most frequent comorbidities found in ICP patients were obesity, overweight and preeclampsia. Surprisingly, high percentage of ICP patients did not respond to UDCA treatment independently of the BMI group to which they belonged. CONCLUSION: The data suggest that ICP contribute to placental lesions. In addition, in patients with normal weight, an increase of chorangiosis and a reduced accelerated villous maturation without syncytial knots were observed in comparison with overweight and obese patients. It is necessary to improve the medical strategies in the treatment and liver disfunction surveillance of ICP patients.
Assuntos
Colestase Intra-Hepática , Pré-Eclâmpsia , Complicações na Gravidez , Gravidez , Feminino , Humanos , Placenta/patologia , Índice de Massa Corporal , Sobrepeso/epidemiologia , Estudos Retrospectivos , Complicações na Gravidez/epidemiologia , Colestase Intra-Hepática/diagnóstico , Colestase Intra-Hepática/epidemiologia , Colestase Intra-Hepática/patologia , Obesidade/diagnóstico , Obesidade/epidemiologiaRESUMO
SUMMARY OBJECTIVE: This study aimed to evaluate the effectiveness of fetal left ventricular modified myocardial performance index in predicting adverse perinatal outcomes for intrahepatic cholestasis of pregnancy. METHODS: A cross-sectional study was conducted, including 51 women with intrahepatic cholestasis of pregnancy and 80 healthy controls. Using Doppler ultrasonography, E-wave, A-wave, isovolumetric contraction time, isovolumetric relaxation time, and ejection time were recorded and the left ventricular modified myocardial performance index was measured. RESULTS: Findings showed that the mean left ventricular modified myocardial performance index, isovolumetric contraction time, and isovolumetric relaxation time values were statistically significantly higher while the ejection time and E/A ratios were statistically significantly lower in the intrahepatic cholestasis of pregnancy group than the control group. In the intrahepatic cholestasis of pregnancy group, a statistically significant positive correlation was found between left ventricular modified myocardial performance index and adverse perinatal outcomes in the intrahepatic cholestasis of pregnancy group (r=0.478, p<0.001), while a statistically significant negative correlation was found between the E/A ratio and adverse perinatal outcomes (r=-0.701, p<0.001). CONCLUSIONS: For intrahepatic cholestasis of pregnancy cases, high fetal left ventricular modified myocardial performance index values were an indicator of ventricular dysfunction, and this correlated with negative perinatal outcomes.
RESUMO
AIM: To analyze the presence of fetal myocardial dysfunction in intrahepatic cholestasis of pregnancy (ICP) at diagnosis. METHODS: This prospective cohort study included 49 pregnant participants with ICP at diagnosis and 49 nonaffected controls from a single public hospital. ICP was diagnosed based on clinical symptoms after excluding other causes of pruritus and presence of autoimmune diseases. Total bile acids were not obtained in this cohort. ICP pregnancies were assessed with a functional echocardiography at diagnosis including PR-interval, isovolumetric contraction time (ICT), ejection time (ET), and isovolumetric relaxation time (IRT) for electrical, systolic, and diastolic function, respectively. Controls were assessed at recruitment. Perinatal outcomes were obtained from delivery books. The main outcome was the presence of PR-interval prolongation or first-degree fetal heart block, and echographic signs of diastolic and systolic dysfunction. RESULTS: Compared to controls, ICP were above upper limit in conjugated bilirubin (2.0% vs. 20.4%; p = 0.008), aspartate aminotransferase (2.0% vs. 24.5%; p = 0.002), and alanine aminotransferase (4.1% vs. 28.6%; p = 0.002). ICP was associated with a higher PR-interval (130 ± 12 ms vs. 121 ± 6 ms; p < 0.0001) with five first-degree fetal heart blocks. IRT was significantly higher in ICP (42 ± 6 ms vs. 37 ± 5 ms; p = 0.0001), with no differences in ICT and ET. PR-interval trend was only positively correlated with IRT in ICP pregnancies (p = 0.04 and p = 0.34, in ICP and controls, respectively). CONCLUSIONS: Our study demonstrates that fetuses affected by maternal ICP are associated with electrical and diastolic myocardial dysfunction. More studies focused on antenatal and postnatal functional echocardiography are necessary to validate our results and consider these markers in the clinical management of ICP pregnancies.
Assuntos
Colestase Intra-Hepática , Cardiopatias , Complicações na Gravidez , Ácidos e Sais Biliares , Colestase Intra-Hepática/complicações , Colestase Intra-Hepática/diagnóstico por imagem , Estudos de Coortes , Feminino , Feto , Humanos , Gravidez , Complicações na Gravidez/diagnóstico , Estudos ProspectivosRESUMO
Se describe los casos de tres pacientes a quien se les realiza diagnóstico de colestasis intrahepática del embarazo (CIE) de aparición temprana. En dos de ellos el diagnóstico se relacionó con infección por el virus de la hepatitis C (VHC). Reconocer que esta enfermedad puede presentarse de manera temprana en el embarazo y su relación con la infección por el VHC es fundamental para hacer un diagnóstico oportuno de ambas enfermedades y tomar las conductas terapéuticas adecuadas, mejorando así el pronóstico materno y fetal.
It is of great importance to acknowledge that this disease can occur early in pregnancy and that its relationship with HCV infection is a key point for a prompt diagnosis, allowing taking timely appropriate therapeutic decisions, aimed at improving the fetal prognosis.
Descrevemos os casos de três pacientes com diagnóstico de colestase intra-hepática da gravidez de início precoce. Em dois deles o diagnóstico estava relacionado à infecção pelo vírus da hepatite C (VHC). Reconhecer que esta doença pode se manifestar precocemente na gravidez e sua relação com a infecção pelo VHC é fundamental para fazer um diagnóstico oportuno de ambas as doenças e assumir condutas terapêuticas adequadas, melhorando assim o prognóstico materno e fetal.
Assuntos
Humanos , Feminino , Gravidez , Adulto , Complicações Infecciosas na Gravidez/diagnóstico , Prurido , Colestase Intra-Hepática/diagnóstico , Colestase Intra-Hepática/etiologia , Hepatite C/complicações , Segundo Trimestre da Gravidez , Primeiro Trimestre da Gravidez , Ácido Ursodesoxicólico/uso terapêutico , Clorfeniramina/uso terapêutico , Colestase Intra-Hepática/tratamento farmacológico , Hepatite C/diagnóstico , Diagnóstico PrecoceRESUMO
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy specific liver disease characterized by pruritus, elevated serum bile acids and abnormal liver function that may be associated with severe adverse pregnancy outcomes. We previously reported that plasma coenzyme Q10 (CoQ10) is decreased in women with ICP as it is its analogue coenzyme Q9 (CoQ9) in rats with ethinyl estradiol (EE)-induced cholestasis. The aim of the present study was to evaluate the possible therapeutic role of CoQ10 in experimental hepatocellular cholestasis and to compare it with ursodeoxycholic acid (UDCA) supplementation. Bile acids, CoQ9, CoQ10, transaminases, alkaline phosphatase, retinol, α-tocopherol, ascorbic acid, thiobarbituric acid reactive substances, carbonyls, glutathione, superoxide dismutase and catalase were assessed in plasma, liver and/or hepatic mitochondria in control and cholestatic rats supplemented with CoQ10 (250 mg/kg) administered alone or combined with UDCA (25 mg/kg). CoQ10 supplementation prevented bile flow decline (P < 0.05) and the increase in serum alkaline phosphatase and bile acids, particularly lithocholic acid (P < 0.05) in cholestatic rats. Furthermore, it also improved oxidative stress parameters in the liver, increased both CoQ10 and CoQ9 plasma levels and partially prevented the fall in α-tocopherol (P < 0.05). UDCA also prevented cholestasis, but it was less efficient than CoQ10 to improve the liver redox environment. Combined administration of CoQ10 and UDCA resulted in additive effects. In conclusion, present findings show that CoQ10 supplementation attenuated EE-induced cholestasis by promoting a favorable redox environment in the liver, and further suggest that it may represent an alternative therapeutic option for ICP.
Assuntos
Colestase Intra-Hepática/tratamento farmacológico , Suplementos Nutricionais , Complicações na Gravidez/tratamento farmacológico , Ubiquinona/análogos & derivados , Animais , Catalase/metabolismo , Colestase Intra-Hepática/metabolismo , Feminino , Glutationa/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Gravidez , Complicações na Gravidez/metabolismo , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Ubiquinona/farmacologia , Ubiquinona/uso terapêutico , Ácido Ursodesoxicólico/uso terapêuticoRESUMO
Liver disease during pregnancy is more common than expected and may require specialized intervention. It is important to determine if changes in liver physiology may develop into liver disease, to assure early diagnosis. For adequate surveillance of mother-fetus health outcome, liver disease during pregnancy might require intervention from a hepatologist. Liver diseases have a prevalence of at least 3% of all pregnancies in developed countries, and they are classified into two main categories: related to pregnancy; and those non- related that are present de novo or are preexisting chronic liver diseases. In this review we describe and discuss the main characteristics of those liver diseases associated with pregnancy and only some frequent pre-existing and co-incidental in pregnancy are considered. In addition to the literature review, we compiled the data of liver disease occurring during pregnancies attended at the National Institute of Perinatology in Mexico City in a three-year period. In our tertiary referral women hospital, liver disease was present in 11.24 % of all pregnancies. Associated liver disease was found in 10.8% of all pregnancies, mainly those related to pre-eclampsia (9.9% of pregnancies). Only 0.56% was due to liver disease that was co-incidental or preexisting; the acute or chronic hepatitis C virus was the most frequent in this group (0.12%). When managing pregnancy in referral hospitals in Latin America, it is important to discard liver alterations early for adequate follow up of the disease and to prevent adverse consequences for the mother and child.
Assuntos
Hepatopatias/terapia , Complicações na Gravidez/terapia , Síndrome de Budd-Chiari/epidemiologia , Síndrome de Budd-Chiari/fisiopatologia , Síndrome de Budd-Chiari/terapia , Colestase Intra-Hepática/epidemiologia , Colestase Intra-Hepática/fisiopatologia , Colestase Intra-Hepática/terapia , Fígado Gorduroso/epidemiologia , Fígado Gorduroso/fisiopatologia , Fígado Gorduroso/terapia , Feminino , Síndrome HELLP/epidemiologia , Síndrome HELLP/fisiopatologia , Síndrome HELLP/terapia , Hepatite Viral Humana/epidemiologia , Hepatite Viral Humana/fisiopatologia , Hepatite Viral Humana/terapia , Degeneração Hepatolenticular/epidemiologia , Degeneração Hepatolenticular/fisiopatologia , Degeneração Hepatolenticular/terapia , Humanos , Hiperêmese Gravídica/epidemiologia , Hiperêmese Gravídica/fisiopatologia , Hiperêmese Gravídica/terapia , Hipertensão Portal/epidemiologia , Hipertensão Portal/fisiopatologia , Hipertensão Portal/terapia , Recém-Nascido , Cirrose Hepática/epidemiologia , Cirrose Hepática/fisiopatologia , Cirrose Hepática/terapia , Hepatopatias/epidemiologia , Hepatopatias/fisiopatologia , Transplante de Fígado , México/epidemiologia , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/fisiopatologia , Pré-Eclâmpsia/terapia , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/fisiopatologia , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/fisiopatologia , Complicações Infecciosas na Gravidez/terapia , Centros de Atenção TerciáriaRESUMO
INTRODUCTION AND AIM: Matrix metalloproteinase (MMP)-2 and MMP-9 are reported to participate in several pregnancy-related diseases, including intrahepatic cholestasis of pregnancy (ICP), which is a severe liver disorder in pregnant women. Meanwhile, ample evidences have demonstrated that celastrol inhibits the activity and expression of MMPs. The present study aims to examine the effect of celastrol to alleviate symptoms of ICP in rat model. MATERIAL AND METHODS: By inducing ICP with 17 - ethinylestradiol in pregnant female rats, we assessed the impact of celastrol administration on symptoms of ICP, such as the rate of bile flow, the level of total bile acids (TBA), and the activities of MMP-2 and -9. Furthermore, the correlations between the levels of MMPs with the examined ICP symptoms were investigated. RESULTS: In rats with ICP, both MMP-2 and -9 exhibited significantly elevated activities, which were inhibited by the administration of celastrol. Furthermore, ICP symptoms such as bile flow rate and total TBA were restored by celastrol. Lastly, there were strong correlations between levels of the two MMPs and TBA. CONCLUSION: Our findings described for the first time the effects of celastrol to attenuate ICP symptoms through an inhibition of both MMP-2 and -9, providing evidence for a potential role of celastrol as a new drug for the treatment of ICP.
Assuntos
Colestase Intra-Hepática/tratamento farmacológico , Metaloproteinase 2 da Matriz/efeitos dos fármacos , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Inibidores de Metaloproteinases de Matriz/uso terapêutico , Complicações na Gravidez/tratamento farmacológico , Prenhez , Triterpenos/uso terapêutico , Animais , Colestase Intra-Hepática/diagnóstico , Colestase Intra-Hepática/enzimologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Triterpenos Pentacíclicos , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/enzimologia , Ratos , Ratos Sprague-Dawley , TripterygiumRESUMO
Introducción: la colestasis intrahepática del embarazo es una afección de espectro clínico-analítico variable de alto riesgo para el feto. Objetivo: identificar la expresividad clínica, bioquímica y los resultados perinatales en pacientes con colestasis intrahepática del embarazo. Método: estudio observacional descriptivo prospectivo, de marzo de 2012 a febrero de 2014 en el Hospital Vladimir Ilich Lenin, de Holguín, Cuba. De 68 pacientes ingresadas con sospecha de afección hepatobiliar, 43 con colestasis del embarazo clasificaron bajo criterios de selección muestral. Los datos procedieron del interrogatorio, examen físico e historias clínicas. Se emplearon los estadígrafos U de Mann-Whitney y Test de Fisher. La clínica se especificó como de mayor o menor severidad y el desenlace perinatal, favorable o desfavorable. Resultados: 58,1% fueron recién nacidos pretérmino; 25,6% con bajo peso al nacer y 23,3% con bajo Apgar. La alaninoaminotransferasa y aspartatoaminotransferasa fueron los analitos con mayor aumento promedio, con 3,2 y 2,2 veces por encima del límite superior normal, respectivamente. Las cifras de alaninoaminotransferasa, aspartatoaminotransferasa, la bilirrubina y el tiempo de protrombina fueron significativamente mayores en el grupo con mayor severidad del cuadro clínico para un 37,2% de la muestra de bilirrubina y triglicéridos, en el grupo con desenlace perinatal desfavorable en un 74,4%. Se produjo una asociación significativa (p = 0,003) entre la severidad de cuadro clínico y el desenlace perinatal. Conclusiones: los resultados de este estudio abren las puertas a futuras investigaciones de diseño más riguroso, con vistas a identificar predictores clínicos y bioquímicos, de peor pronóstico fetal en nuestro medio.
Introduction: intrahepatic cholestasis of pregnancy, a condition with variable clinical and analytic expressions, involves risk for the fetus. Objective: to identify the clinical, biochemical expression and perinatal outcome in patients with cholestasis intrahepatic of pregnancy. Method: descriptive observational prospective investigation from March 2012 to February 2014, at Vladimir Ilich Lenin Hospital, in Holguín. A group of 43 patients with intrahepatic colestasis of pregnancy, out of 68 admitted patients with hepatobiliary conditions with selection criteria, were included. Interrogatory, physical examination and clinical records were data sources. Mann-Whitney U and Fisher statistical tests were applied. Clinical manifestations were classified into milled or severe, and perinatal outcome in favorable or unfavorable. Results: the 58.1% were preterm newborns; 25.6% had low birth weight and 23.3% had a low Apgar score. Alanine aminotransferase and aspartate aminotransferase were the most increased laboratory tests with 3.2 y 2.2 times over the upper limit of normal, each. Alanine aminotransferase, aspartate aminotransferase, bilirubin and prothrombin time values were significantly higher in the most symptomatic group with 37.2%. Bilirubin and triglycerides were significantly higher in the group with unfavorable perinatal outcome with 74.4%. There was a significant association (p = 0.003) between the severity of clinical manifestations and perinatal outcome. Conclusions: present study results favor future research development and rigorous clinical and biochemical predictors designs for worst fetal prognosis, in our clinical settings.
RESUMO
ABSTRACT Intrahepatic cholestasis of pregnancy (ICP) is a severe liver disease uniquely occurring during pregnancy. In this study we aimed to identify novel biomarker for the diagnosis of ICP in Chinese population. 50 healthy pregnant women, 50 mild ICP patients and 48 severe ICP patients were enrolled for this study. Liver function tests, including serum total bilirubin, direct bilirubin, alanine transaminase, aspartate aminotransferase and cholyglycine, were performed in all participants. After an overnight fast serum levels of total bile acids (TBA), matrix metalloproteinase (MMP)-2 and MMP-9 were measured, and their correlation with liver function tests were analyzed. The observed increase in serum TBA in ICP patients was not statistically significant which made it unreliable for diagnosis of ICP in Chinese population. On the other hand, both MMP-2 and MMP-9 serum levels exhibited a progressive and significant elevation in mild and severe ICP patients compared with healthy pregnant women, which also positively correlated with liver function tests. Serum levels of both MMP-2 and MMP-9 could be reliably used as laboratory abnormalities for accurate diagnosis and sensitive grading of ICP in Chinese population.