Liver Disease in Pregnancy

March 25, 2020 updated by: King's College Hospital NHS Trust

EASL: European Registry of Liver Disease in Pregnancy

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.

Study Overview

Detailed 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.

Study Type

Observational

Enrollment (Anticipated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

Liver Diseases in pregnancy represent rare disorders and the numbers of patients affected in the overall population is low and therefore, it has proven difficult to generate reliable data. For example, the numbers of patients affected with these conditions in Europe are as follows:

  • Acute Fatty Liver affects 1:20,000 pregnant women
  • Severe Cholestasis - 1:3,000 pregnant women
  • Severe haemolysis, elevated liver enzymes and low platelets (HELLP syndrome) requiring transfer to a liver transplant centre or specialised hepatopancreatobiliary(HPB) centre at best estimate represents less than 0.01% of pregnancies.

Patients with pre-existing cirrhosis and pregnancy represent approximately 0.003% of pregnancies, yet, to-date, less than 5 reliable publications exist in the literature to inform patient management.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Cirrhosis in pregnancy
Cirrhotic patients with a confirmed pregnancy will be placed into Cohort 1.
Pregnancy-associated liver diseases
Patients who develop Acute Fatty Liver of Pregnancy, HELLP Syndrome / Intrahepatic Cholestasis of pregnancy will be placed into Cohort 2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall maternal and fetal health during pregnancy and post-delivery in females with liver disease
Time Frame: Data to be collected from pre-pregnancy to 3 months post-delivery
Data from 100 patients will be collected across the EU who have either pre-exisiting cirrhosis or one of the three pregnancy-associated liver diseases that are to be studied in this protocol (AFLP, HELLP, ICP)
Data to be collected from pre-pregnancy to 3 months post-delivery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Michael Heneghan, King's College Hospital NHS Trust

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 9, 2019

Primary Completion (ANTICIPATED)

April 8, 2024

Study Completion (ANTICIPATED)

April 8, 2025

Study Registration Dates

First Submitted

February 5, 2019

First Submitted That Met QC Criteria

February 6, 2019

First Posted (ACTUAL)

February 7, 2019

Study Record Updates

Last Update Posted (ACTUAL)

March 27, 2020

Last Update Submitted That Met QC Criteria

March 25, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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