Dr Emer Fitzpatrick (Liver)

Dr Emer Fitzpatrick - 2015 BSPGHAN / Core Development Award
Dr Emer Fitzpatrick – 2015 Core / BSPGHAN Development Award

Institution: King’s College London

Title: LiverMultiScanTM for the assessment of graft fibrosis in children post-liver transplant

Project Start Date: 9 November 2015

Completion Date: 8 May 2017

Summary:

Liver transplantation in children is a lifesaving procedure. Improvements in surgical techniques and post-transplant care have led to a survival of greater than 80% at 10 years following transplant. A number of recent studies have highlighted problems with the transplant at 5 and 10 years however, and inflammation and scarring are present in the vast majority of transplanted livers. The major concern is that this injury will progress and the organ will cease to function properly with time. If changes are made to immunosuppressive medication, progression of the injury can potentially be modified and even reversed. A liver biopsy is generally needed to detect this inflammation and scarring, as in the majority of cases the patient is otherwise well with normal blood tests. Liver biopsy is an invasive procedure and risks include bleeding and, rarely, death. Routine biopsies are done in some centres to assess the liver at intervals after transplant however this is not universally accepted, particularly in completely well children.

An alternative would be to use non-invasive methods to assess the transplanted organ. Routine blood tests and scans are not accurate enough for this purpose. A recent study using MRI to assess scarring in adult patients with liver disease has found it to have excellent correlation with liver biopsy. The researchers’ aim was to use this technique (which is quick, pain free and does not involve any radiation) in children who have had a transplant. MRI using this software system may have more promise than other non-invasive methods for this purpose.

The researchers investigated the use of MRI scans to detect the presence of scarring and inflammation in the transplanted liver, and assessed how effective that method was compared to using liver biopsies.

This particular study was designed as a pilot that would provide sufficient data to plan a larger multi-centre (European) study. As this type of study involving MRI has not been done before in the UK specifically on children who had received a liver transplant, the researchers wanted to check how feasible it was to carry out and what the likelihood was of recruiting sufficient patients in the 2 years planned for the larger study.

The pilot demonstrated that the larger study was feasible. The researchers showed it was possible to recruit children within the allocate time frame; they also showed children as young as 8 years old were capable of undergoing the MRI scan without sedation.

The pilot study also highlighted a number of alterations to the protocol (the steps followed by the study) that needed to be made before proceeding with the larger study. The logistics and timing of the MRI scans and other investigations were trialed in different ways and refined, resulting in a clearer protocol. the children and their families also made suggestions to make the protocol more user friendly.

The researchers also tested different ways to assess (score) the liver tissue samples obtained from the biopsies, to help them determine the best scoring system to use in the larger trial.

The researchers were able to obtained additional funds from the European Union (the Horizon 2020 funding scheme) to carry out the larger study, which has just started. This study will recruit 200 children from 4 centres across Europe. The UK centre, represented by King’s College London, which is the institution where Dr Fitzpatrick is based, will be responsible for recruiting 50 children for the study. They will also be responsible for analysing all the tissue samples obtained from biopsies from all the 4 centres.

The researchers noted that the pilot study was fundamental in obtaining enough preliminary data to secure the funding for the larger study.

Ultimately the aim of this pilot and the planned larger study is to devise a test with the best diagnostic accuracy for monitoring livers after transplant, thus saving numerous liver biopsies and potentially maintaining good function of the transplanted liver beyond the 10 year mark.

The Joint Core-BSPGHAN award has enabled us to investigate a very promising new MRI based technique that measures inflammation, scarring and fat in the liver without the need for liver biopsy. Children and young people who have had a liver transplant often need quite frequent liver biopsies to tell us what is going on in the liver and understand what we have to do to keep the liver healthy. We hope that this new type of MRI will allow us to detect any problems in the transplanted liver without the risks and discomfort associated with liver biopsy.

Dr Emer Fitzpatrick