Pregnancy-Related Liver Diseases

Previous studies have shown that per- and polyfluoroalkyl substances (PFAS) may have hepatotoxic effects in animals. However, epidemiological evidence in humans, especially pregnant women, is limited. This study aimed to assess the association of single and multiple PFAS exposure with serum markers of liver function in pregnant women. A total of 420 pregnant women from the Guangxi Zhuang Birth Cohort were enrolled from June 2015 to April 2019. Nine PFAS were measured in the maternal serum in early pregnancy. Data for liver function biomarkers, namely, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL), were obtained from medical records. In generalized linear model (GLM), there was a positive association of perfluorooctane sulfonate (PFOS) with ALT, perfluorodecanoic acid (PFDA) and perfluorobutanesulfonic acid (PFBS) with GGT, and perfluorohexane sulfonate (PFHxS) with TBIL and IBIL. In contrast, there was a negative association of perfluoroheptanoic acid (PFHpA) with TBIL. There were inverse U-shaped relationships of PFUnA with ALT and AST and PFDA with ALT by restricted cubic spline. The weighted quantile sum (WQS) regression model revealed the positive effects of the PFAS mixture on GGT, TBIL, DBIL, and IBIL. Bayesian kernel machine regression (BKMR) analysis confirmed that the PFAS mixture was positively associated with GGT, and PFBS was the main contributor. In addition, the BKMR model showed a positive association of individual PFBS with GGT, individual PFHxS with TBIL and IBIL, and a negative association of individual PFHpA with TBIL. Our findings provide evidence of an association between individual PFAS, PFAS mixture and maternal serum markers of liver function during pregnancy. Additionally, these findings also enhance concerns over PFAS exposure on maternal liver function and PFAS monitoring in pregnancy, reducing the effect of maternal liver dysfunction on maternal and infant health.

Pregnancy-related liver diseases are the most frequent cause of liver dysfunction in pregnancy and pose a real threat to fetal and maternal survival. Although hepatobiliary disorders are uncommon in pregnancy, they may be severe enough to cause risk to both the mother and fetus. There are five different types of liver disease that are unique to pregnancy, including hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, preeclampsia, hemolysis, elevated liver enzyme, and low platelet count syndrome, and acute fatty liver of pregnancy. Ultrasound, computed tomography, and magnetic resonance imaging play important roles in the rapid diagnosis and evaluation of complications. An accurate diagnosis can guide further treatment or the induction of labor to prevent intrauterine fetal death. This review highlights the pathogenesis, clinical features, imaging features, and treatment of pregnancy-related liver diseases with the aim of enhancing awareness of these rare but potentially life-threatening diseases of pregnancy.

El término colestasis se refiere a la retención de ácidos biliares ya sea dentro del hepatocito o en los ductos biliares de cualquier calibre. Por laboratorio, se define por la elevación de fosfatasa alcalina arriba de 1.67 veces su valor normal. Las enfermedades colestásicas pueden asociarse a un proceso inflamatorio de la glándula hepática que provoca destrucción de los hepatocitos (hepatitis), a ictericia (coloración amarillenta de piel y mucosas asociada a elevación en niveles séricos de bilirrubinas) o ambas, aunque estos tres conceptos no deben considerarse sinónimos. Los padecimientos colestásicos pueden clasificarse como intra o extrahepáticos dependiendo de su etiología, y esto es importante para elegir los estudios diagnósticos adecuados y la terapéutica indicada en cada uno de los casos. Una historia clínica completa, aunada a exploración física exhaustiva y estudios iniciales básicos como el ultrasonido hepático y las pruebas de funcionamiento del hígado, pueden ayudar al clínico a decidir el camino a seguir al enfrentarse al paciente con colestasis. La Asociación Mexicana de Hepatología, la Asociación Mexicana de Gastroenterología y la Asociación Mexicana de Endoscopia Gastrointestinal decidieron trabajar en el primer posicionamiento científico mexicano sobre este tema.

The term cholestasis refers to bile acid retention, whether within the hepatocyte or in the bile ducts of any caliber. Biochemically, it is defined by a level of alkaline phosphatase that is 1.67-times higher than the upper limit of normal. Cholestatic diseases can be associated with an inflammatory process of the liver that destroys hepatocytes (hepatitis), with jaundice (yellowing of the skin and mucus membranes, associated with elevated serum bilirubin levels), or with both, albeit the three concepts should not be considered synonymous. Cholestatic diseases can be classified as intrahepatic or extrahepatic, depending on their etiology. Knowing the cause of the condition is important for choosing the adequate diagnostic studies and appropriate treatment in each case. A complete medical history, together with a thorough physical examination and basic initial studies, such as liver ultrasound and liver function tests, aid the clinician in deciding which path to follow, when managing the patient with cholestasis. In a joint effort, the Asociación Mexicana de Hepatología (AMH), the Asociación Mexicana de Gastroenterología (AMG) and the Asociación Mexicana de Endoscopia Gastrointestinal (AMEG) developed the first Mexican scientific position statement on said theme.

Intrahepatic cholestasis of pregnancy (ICP) increases the risk of adverse pregnancy outcomes. This study aimed to explore the association between serum syndecan-1 and glypican-3 levels and the adverse perinatal outcome as well as the responses to the treatment of ursodeoxycholic acid (UDCA).

This prospective, case control study included 88 pregnant women (44 women with ICP and 44 healthy controls). The primary end points were the perinatal outcome and the response to UDCA therapy. A logistic regression model was used to identify the independent risk factors of adverse pregnancy outcomes and reduced response to UDCA therapy.

Women with ICP had significantly higher serum syndecan-1 (1.27 ± 0.36 ng/mL vs. 0.98 ± 0.50 ng/mL; P = 0.003), glypican-3 (1.78 ± 0.13 ng/mL vs.1.69 ± 0.16 ng/mL; P = 0.004), AST (128.59 ± 1.44 vs. 13.29 ± 1.32 U/L; P < 0.001), and ALT (129.84 ± 1.53 vs. 8.00 ± 3.67 U/L; P < 0.001) levels compared with the controls. The increased levels of syndecan-1 (OR = 4.715, 95% CI: 1.554–14.310; P = 0.006), glypican-3 (OR = 8.465, 95% CI: 3.372–21.248; P = 0.007), ALT (OR = 1.382, 95% CI: 1.131–1.690; P = 0.002), and postprandial bile acid (PBA) (OR = 3.392, 95% CI: 1.003–12.869; P = 0.026) were correlated to ICP. The adverse neonatal outcome was related to increased glypican-3 (OR = 4.275, 95% CI: 2.726–5.635; P = 0.039), and PBA (OR = 3.026, 95% CI: 1.069–13.569; P = 0.037). Increases of syndecan-1 (OR = 7.464, 95% CI: 2.130–26.153, P = 0.017) and glypican-3 (OR = 6.194, 95% CI: 2.951–13.002; P = 0.025) were the risk factors of decreased response to UDCA treatment.

Syndecan-1 and glypican-3 might be powerful determinants in predicting adverse perinatal outcome in patients with ICP, and they can be used to predict the response to the UDCA treatment.

Thrombocytopenia in pregnancy is relatively common and may have many different etiologies. While some causes of thrombocytopenia, such as incidental thrombocytopenia of pregnancy, have no impact on pregnancy outcomes, others, such as preeclampsia or the syndrome of hemolysis, elevated liver function tests, and low platelets (HELLP) adversely impact both maternal and fetal health. The latter disorders display features that overlap extensively with the primary thrombotic microangiopathies, thrombotic thrombocytopenic purpura (TTP) and the atypical hemolytic-uremic syndrome (aHUS), the incidence of which is increased in pregnancy. Distinguishing these disorders may be difficult, although it is important to do so since the definitive management of the pregnancy-specific disorders involves delivery of the fetus. Recent insights into the mechanisms underlying the diffuse endothelial dysfunction associated with preeclampsia, as well as the role of complement inhibitor gene mutations in HUS and HELLP, offer new approaches to diagnosis and management of these frequently devastating disorders.

Liver dysfunction is common in pregnancy but its association with adverse pregnancy outcomes such as preterm birth (PTB) remains unclear.

A prospective cohort of HBV-infected or uninfected pregnant women attending antenatal care was recruited at Nantong Maternal and Child Health Hospital between January 1, 2012, and June 30, 2016. Liver function tests (LFTs) were monitored through pregnancy. The primary outcomes were PTB and very PTB (delivery prior 37 and 32 weeks' gestation respectively). Poisson regression was used to estimate adjusted risk ratios (RR) for women with HBV infection and LFT abnormalities.

Among 36,755 pregnant women (1,113 HBV carriers and 35,642 non-HBV subjects), 3,519 (9.57%) had abnormal LFTs. The commonest cause for liver dysfunction during pregnancy was non-alcoholic fatty liver diseases (NAFLD, 51.3%). Abnormal aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT) and two folds upper limit of normal total bilirubin (RR and 95%CI: 2.73, 1.30–5.76; 2.24, 1.35–3.31; 2.01, 1.22–3.31 respectively), rather than HBsAg positivity, were identified as independent risk factors for preterm birth. Besides, GGT abnormality was associated with increased risk of very PTB.

We suggest that surveillance of LFTs among pregnant women should be warranted, given the increased risk of PTB.