Clinical trial NCT03834285: Liver Disease in Pregnancy
Official title: EASL: European Registry of Liver Disease in Pregnancy
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Pregnancy Disease
Cirrhosis, Liver
HELLP Syndrome
AFLP - Acute Fatty Liver of Pregnancy
Intrahepatic Cholestasis of Pregnancy
Lead sponsor: King's College Hospital NHS Trust
Sponsor class: OTHER
Collaborators: name: European Association for the Study of the Liver
First posted: 2019-02-07
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall maternal and fetal health during pregnancy and post-delivery in females with liver disease
timeFrame: Data to be collected from pre-pregnancy to 3 months post-delivery
Secondary outcomes:
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
Study officials:
affiliation: King's College Hospital NHS Trust
name: Michael Heneghan
role: STUDY_CHAIR
References: