Liver Disease in Pregnancy

King's College Hospital NHS Trust

Status: Enrolling

Conditions: Intrahepatic Cholestasis of Pregnancy; Pregnancy Disease; Cirrhosis, Liver; AFLP - Acute Fatty Liver of Pregnancy; HELLP Syndrome

Study type: Observational

Funder types: Other

Identifiers

NCT03834285

238575

Details and patient eligibility

About

Liver Diseases in pregnancy represents rare disorders and current data is derived primarily from single centres and retrospective cohorts. Moreover, the population prevalence of these diseases is low and to-date, it has proven difficult to generate reliable data at a patient level.

This is a multi-center, prospective cohort study that will open at 3 centers within the UK; and 4 centers in the European Union. The investigators will aim to collect data and blood samples at various time points, for patients presenting with liver disease during pregnancy. The main rationale behind this study is to establish a platform that enables detailed review of the outcomes of these rare diseases; to help classify and stratify patients according to risk and develop interventional studies and care pathways to improve overall outcome.

Full description

The objectives of the study are as follows:

Primary Objective:

To determine the characteristic physiological and biological changes exhibited by females who develop the following liver diseases during pregnancy.

• Acute fatty liver of pregnancy
• Severe cholestasis of pregnancy
• Severe HELLP syndrome/hypertensive disease
• Pre-existing cirrhosis and pregnancy This will be determined through analysis of the standard of care imaging (Liver Ultrasound and Transient Elastography) and blood results (liver function tests, white blood cells, platelets and scoring systems for assessing the severity of liver disease (ALBI, APRI, FIB4 and ELF scores). These results will be analysed over the course of the participant's pregnancy and again at delivery, to explore any particularly distinguishing parameter changes for each disease group.

Secondary Objectives

1. To determine the change in the reported quality of life of these participants either from diagnosis of pregnancy-associated liver disease or confirmation of pregnancy for pre-existing cirrhotic patients - up to 3 months' post-delivery.
2. To determine the mitochondrial DNA content of blood from patients with Acute Fatty Liver of Pregnancy.
3. Create an associated pan-European bio-resource (whole blood and serum) collection, which will offer an opportunity for ongoing collaborative translational research. Each participant will be given the option of donating additional research samples (15ml) of blood at each visit under the study for the bio-resource.

Data from cirrhotic patients will be collected from pre-pregnancy and during the first, second and third trimesters as well as at delivery and post-partum. Data from patients with AFLP/HELLP/ICP will be collected from pre-diagnosis, at first presentation of liver disease, at peak of liver disease, during the recovery period from peak liver disease as well as at delivery and post-partum.

Enrollment: 100 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Female patients older than 18 years of age, willing and able to sign written informed consent.

2. Pregnant and presenting with any one of the following conditions (confirmed by local diagnosis):

   • Acute fatty liver of pregnancy
   • Severe cholestasis of pregnancy
   • Severe HELLP syndrome /hypertensive disease
   • Pre-existing cirrhosis and pregnancy

3. Able to provide written informed consent

4. Willing to provide access to records to necessary data can be collected.

5. Willing to complete additional quality of life questionnaires as per protocol.

6. Willing to consider donation of optional blood samples as per protocol.

Exclusion criteria

1. Unable to provide written informed consent

Trial design

100 participants in 2 patient groups

Cirrhosis in pregnancy

Description:

Cirrhotic patients with a confirmed pregnancy will be placed into Cohort 1.

Pregnancy-associated liver diseases

Description:

Patients who develop Acute Fatty Liver of Pregnancy, HELLP Syndrome / Intrahepatic Cholestasis of pregnancy will be placed into Cohort 2.