Re-evaluating diagnostic thresholds for intrahepatic cholestasis of pregnancy: case-control and cohort study.

OBJECTIVE: To determine the optimal total serum bile acid (TSBA) threshold and sampling time for accurate intrahepatic cholestasis of pregnancy (ICP) diagnosis. DESIGN: Case-control, retrospective cohort studies. SETTING: Antenatal clinics, clinical research facilities. POPULATION: Women with ICP or uncomplicated pregnancies. METHODS: Serial TSBA measurements were performed pre-/postprandially in 42 women with ICP or uncomplicated pregnancy. Third-trimester non-fasting TSBA reference ranges were calculated from 561 women of black, south Asian and white ethnicity. Rates of adverse perinatal outcomes for women with ICP but peak non-fasting TSBA below the upper reference range limit were compared with those in healthy populations. MAIN OUTCOME MEASURES: Sensitivity and specificity of common TSBA thresholds for ICP diagnosis, using fasting and postprandial TSBA. Calculation of normal reference ranges of non-fasting TSBA. RESULTS: Concentrations of TSBA increased markedly postprandially in all groups, with overlap between healthy pregnancy and mild ICP (TSBA <40 µmol/l). The specificity of ICP diagnosis was higher when fasting, but corresponded to <30% sensitivity for diagnosis of mild disease. Using TSBA ≥40 µmol/l to define severe ICP, fasting measurements identified 9% (1/11), whereas non-fasting measurements detected over 91% with severe ICP. The highest upper limit of the non-fasting TSBA reference range was 18.3 µmol/l (95% confidence interval: 15.0-35.6 µmol/l). A re-evaluation of published ICP meta-analysis data demonstrated no increase in spontaneous preterm birth or stillbirth in women with TSBA <19 µmol/l. CONCLUSIONS: Postprandial TSBA levels are required to identify high-risk ICP pregnancies (TSBA ≥40 µmol/l). The postprandial rise in TSBA in normal pregnancy indicates that a non-fasting threshold of ≥19 µmol/l would improve diagnostic accuracy. TWEETABLE ABSTRACT: Non-fasting bile acids improve the diagnostic accuracy of intrahepatic cholestasis of pregnancy diagnosis.

A Narrative Review of Oxidative Stress and Liver Disease in Pregnancy: The Role of Antioxidants.

Pregnancy brings numerous physiological changes to the body of the pregnant woman. Liver diseases in pregnancy contribute to increased oxidative stress, disrupting the delicate balance between reactive oxygen species and antioxidant defence. Antioxidant supplementation may have potential benefits in addressing pregnancy-related liver disorders, such as HELLP (haemolysis, elevated liver enzymes, low platelet count) and preeclampsia-associated liver dysfunction in pregnancy. The purpose of this narrative review is to review the evidence regarding oxidative stress in liver disorders during pregnancy and the role of antioxidants in alleviating oxidative stress and its effect on maternal and foetal outcomes. A narrative review study design involved a comprehensive search across three scientific databases: PubMed, Embase, and MEDLINE, published in the last 20 years. The searches were performed up to January 2024. Thirty-two studies were included in the narrative review. The most studied antioxidants were vitamins (vitamin C and E) for their role in clinical treatment, prophylaxis, and clearing surrogate oxidative stress markers. The majority of studies were on preeclampsia. Though the existing literature is not robust, available evidence suggests that antioxidant supplementation may have potential benefits in addressing pregnancy-related liver disorders, such as HELLP and preeclampsia-associated liver dysfunction in pregnancy. However, there is a need to establish consistent protocols, ethical standards, and well-designed clinical trials to clarify the timing and dosage of antioxidants in pregnancy. Antioxidants may alleviate the oxidative stress in various liver disorders during pregnancy, which still needs to be studied further for their clinical relevance.

Acute Fatty Liver of Pregnancy: A Diagnostic Challenge.

Acute fatty liver of pregnancy (AFLP) is a rare, catastrophic disease affecting women in the third trimester of pregnancy or the postpartum period. We report a case of 24-year-old G2A1 with GA of 35 weeks who presented with amenorrhea, nausea, fever, vomiting, headache and yellowness of eyes. The patient was diagnosed with severe preeclampsia with Intrauterine death (IUD) with hemolysis elevated liver enzymes low platelets (HELLP). Investigations showed hypoglycemia, low platelet count, and raised liver enzymes with an altered coagulation profile. The patient was kept in the Medicine Intensive care unit, induction was done with misoprostol, and she delivered an IUD baby. The condition of the patient deteriorated, and she developed pulmonary edema. Thus, she was intubated. Ultrasonography (USG) of the liver showed altered echotexture. The condition of the patient was then improved. AFLP requires a high index of suspicion for early diagnosis. Hypoglycemia in a pregnant woman without overt /gestational diabetes mellitus along with deranged liver panels and thrombocytopenia gives a clue in diagnosing AFLP. Timely diagnosis and intervention can reduce both maternal and fetal morbidity and mortality.

Indian National Association for the Study of the Liver-Federation of Obstetric and Gynaecological Societies of India Position Statement on Management of Liver Diseases in Pregnancy.

Liver diseases occurring during pregnancy can be serious and can progress rapidly, affecting outcomes for both the mother and fetus. They are a common cause of concern to an obstetrician and an important reason for referral to a hepatologist, gastroenterologist, or physician. Liver diseases during pregnancy can be divided into disorders unique to pregnancy, those coincidental with pregnancy, and preexisting liver diseases exacerbated by pregnancy. A rapid differential diagnosis between liver diseases related or unrelated to pregnancy is required so that specialist and urgent management of these conditions can be carried out. Specific Indian guidelines for the management of these patients are lacking. The Indian National Association for the Study of the Liver (INASL) in association with the Federation of Obstetric and Gynaecological Societies of India (FOGSI) had set up a taskforce for development of consensus guidelines for management of patients with liver diseases during pregnancy, relevant to India. For development of these guidelines, a two-day roundtable meeting was held on 26-27 May 2018 in New Delhi, to discuss, debate, and finalize the consensus statements. Only those statements that were unanimously approved by most members of the taskforce were accepted. The primary objective of this review is to present the consensus statements approved jointly by the INASL and FOGSI for diagnosing and managing pregnant women with liver diseases. This article provides an overview of liver diseases occurring in pregnancy, an update on the key mechanisms involved in its pathogenesis, and the recommended treatment options.