Liver Disease Research

CLDF has a strong track record of supporting research, with over £9 million of research funding delivered since 1980. Most of this money has been donated by families, friends, relatives and other supporters.

Thanks to Children’s Liver Disease Foundation’s amazing fundraisers we are able to provide funding for a variety of projects exploring childhood liver disease. CLDF has a strong track record of supporting research, with over £9 million of research funding delivered since 1980. Most of this money has been donated by families, friends, relatives and other supporters. Research not only enhances our understanding of childhood liver disease and improves available treatments but it gives children, young people and their families hope for a better future.

CLDF funds a wide range of projects including clinical, lab based and social science research all focused on aspects of childhood liver disease. The decision to award funding is made by CLDF’s Scientific Committee. They are a group of experts who ensure research funded by CLDF is rigorous and is most likely to have a positive impact on children with liver disease and their families. We can only continue to support research because of the money you raise. We don’t receive any NHS funding and completely rely upon donations. If you would like to support us to continue funding research into childhood liver disease you can donate here or find out more about fundraising and how you can get involved. CLDF is a member of the Association of Medical Research Charities.

Priorities for paediatric liver research funding 2015 -2020

The following are identified as priority areas for research funding:-

  • Biobank and bio-markers
  • National Paediatric Liver Diseases Register
  • National Register of long term outcome for liver transplant
  • Research into primary paediatric liver disease (all conditions)
  • Prevalence/epidemiology
  • Aetiology
  • Different treatment modes
  • Outcomes
  • Neonatal cholestasis
  • Outcomes in adults of childhood liver diseases, including liver transplantation
  • Clinical research including relevant drug trials in children and the long term effects of medication
  • Social research for all ages and including adults diagnosed in childhood to include definition, measures and interventions in the following areas:-
  • Quality of life
  • Survivorship
  • Transition to adult services
  • Compliance and adherence

Underlying principles in research delivery

In funding and delivering its research programme, the following underlying principles will be paramount:-

  • CLDF gives preference to multi-centre, collaborative research
  • CLDF encourages research which focuses on added value
  • CLDF is keen to identify how and where its research portfolio fits into the wider research programme and agenda
  • CLDF recognises that given its funding available it is more likely to fund work in the early stages of research topic continuum, particularly when it is one which is capable of being taken from bench to bedside. It will monitor its programme for up to seven years beyond the end of a project
  • CLDF expects dissemination of outputs and outcomes to both lay and professional audiences
  • CLDF recognises the importance of the national and international research picture including the National Institute for Health Research (NIHR) and will take note of topical issues in applying its research priorities
  • CLDF will expect its Principal Investigators to know of and apply to relevant networks and schemes beyond CLDF funded research
  • Research teams are expected to think ‘outside the box’ and are expected to consider enabling European and other collaborations

CLDF Research Funding Mechanisms

CLDF will fund research using the following mechanisms:

  • Project Grants encompassing:
  • Up to 3 years funding
  • Staff costs
  • Consumables costs
  • CLDF PhD student fellowships
  • Small Grants Programme

CLDF Research Hub

CLDF will create projects during the strategy period, which increase opportunities for families and young people to learn more and be involved in research within the field. As part of this CLDF will aim to increase formal patient and public involvement in the design of research projects across the sector by creating a Research Hub, for researchers to obtain feedback from families and young people about the projects they are developing. By providing vehicles for such support CLDF could play a role in enabling a greater number of paediatric liver disease related research projects to be funded and undertaken.

Click here to view the Research Hub.

Strategy Review and Development process

This strategy has arisen out of a consultation over a period of nine months and incorporated consultation with the following stakeholders:

  • Young People
  • Parents
  • CLDF Scientific Committee
  • Medical Professionals
  • Trustees

Consultation took place via a variety of routes:

  • Surveys for medical professionals circulated via BSPGHAN and through our own networks.
  • Surveys for parents and young people circulated via social media platforms and direct invitation.
  • A residential consultation weekend with families and young people.
  • Feedback from our 2014 National Conference.
  • One to One meetings with medical, psychology and nursing staff at Kings College Hospital, Birmingham Children’s Hospital and Leeds General Infirmary
  • Discussion and ratification made at Scientific Committee and Trustee Board Meetings.

Use of animals and indirect costs

CLDF complies with the stance of the Association of Medical Research Charities (AMRC) on the use of animals in research as well as with indirect costs. Find out more about the use of animals in research, indirect costs and other policies on the AMRC website.

Funding Research

CLDF offers funding to researchers through a number of different programmes:

  • £10,000 Grants Programme
  • PhD Programme
  • Small Grants Programme

Use of funds

  • Applications will only be accepted for work based in the UK
  • Applications must be in line with the CLDF Research Strategy
  • The Funds can be used widely but applicants must always be able to demonstrate how it can contribute to knowledge in paediatric hepatology
  • Funds will not be awarded retrospectively
See Our Recent Research

CLDF Research Strategy

CLDF has a broad range of interest in the field of paediatric hepatology.  This strategy identifies the priorities for funding in CLDF’s Research Funding Programme for 2015-2020 and further initiatives aimed at supporting research into paediatric hepatology.  The availability of funding will always influence CLDF’s programmes.

This strategy is based upon CLDF’s current and projected income levels.  However, there is flexibility if the situation changes. CLDF will look to fund a PhD Fellowship and a main grants round, alternating on a two year cycle. We will also look to opportunities to work with allied organisations to joint fund the main grants round during the strategy period.

Children’s Liver Disease Foundation Research Grants 2019

Children’s Liver Disease Foundation (CLDF) are funding research grants with an overall aim of encouraging research in liver disease in children and young people. We aim to support preliminary research that will contribute significantly to a subsequent larger research grant proposal. There are no restrictions on the scope of projects, which may focus on; gaining insights into the causes of liver disease or improving diagnosis, management and longer-term outcomes, this can include basic, translational, laboratory, clinical or a social science focus. Awards can be used to pump prime a new project, support an ongoing project. Projects may be stand-alone or linked to one or more existing studies, applications from PhD students for the costs of consumables to undertake projects will also be considered.

Submissions are invited for awards up to a maximum of £10,000. We aim to award a numbers of grants. Funds may be used for any purpose that facilitates the research. This includes buying minor equipment, reagents or consumables, travel expenses required to undertake the research (e.g. visiting research sites, home visits to participants), support staff time and the additional costs paid as a result of releasing the applicant from his/her contracted duties. Projects must be completed within 12-24 months of funds being awarded. Successful applicants must agree to provide an interim progress and final project report, submit the findings for a poster or presentation at a CLDF event and aim to publish the findings if appropriate.

  • PhD Students need to include details of their supervisors alongside their application.
  • Proposals submitted after this deadline will not be considered.
  • Proposals will be reviewed by CLDF’s Scientific Committee.

Click here to download an application form:CLDF Research Grant Application Form 2019

We aim to inform applicants regarding funding during the first week of October 2019.

Proposals must be submitted to Sarah Harrold by email to: om@childliverdisease.org by 5pm on Monday 17th June 2019. If you would like to discuss any aspect of your proposal please contact Alison Taylor  (Chief Executive) ceo@childliverdisease.org

Current Research Projects

Dr Eirini (Serena) Kyrana

Role of Sarcopenia in Paediatric Non-Alcoholic Fatty Liver Disease

Dr Eirini (Serena) Kyrana at Leeds Children’s Hospital, Leeds Teaching Hospitals NHS Trust

Role of Sarcopenia in Paediatric Non-Alcoholic Fatty Liver Disease

What is this study looking at?
Muscle wasting, also known as sarcopenia, has for many years been associated with chronic disease including chronic liver disease. It is now clear that sarcopenia can often exist undetected in the presence of obesity and still exert its harmful effects.

The prevalence of sarcopenia in paediatric NAFLD and its associated risks are unknown.This study will assess the body composition of children with non-alcoholic fatty liver disease.

This will be done by established, simple, painless methods that require minimal cooperation. The study will aim to identify the relationship between sarcopenia and degree of steatosis, fibrosis and inflammation on liver biopsy and any associations with molecules associated with muscle growth, insulin resistance and liver fibrosis.

Why is this research important?
NAFLD has become the most common paediatric chronic liver disease in industrialised countries and in the United States (in adults) the second leading cause for liver transplantation. NAFLD in children provides a pure model of the disease as children have significantly less additional conditions like heart disease and cancer.

Children are also more likely to have a significant benefit from the development of effective interventions. In addition, the benefits for society from treating children, who are carrying this condition into adulthood is also greater.

There has been no previous paediatric study, to our knowledge, exploring the association of sarcopenia with increased fibrosis and/or inflammation in the context of NAFLD. No study in children with NAFLD has investigated the various myokines (products released by muscle cells) and adipokines (protein secreted by body fat) in relation to muscle mass.

This study would help to generate data that would provide the basis for developing larger multicentre studies looking at the effect of interventions like exercise and even interventions like GDF15 stimulators or myostatin inhibitors when they come into practice.

What about the future?
The long-term goal for this study is to gain insight that will provide the basis of successful interventions and potential treatment strategies in the near future.

Successful interventions in childhood would have exponential benefits both for the child and for our society, as NAFLD is a condition carrying significant morbidity and mortality into the future.

Dr Emer Fitzpatrick

Using Nuclear Magnetic Resonance (NMR) Spectroscopy to understand hepatic lipid metabolism in paediatric NAFLD

Dr Emer Fitzpatrick at King’s College Hospital

Using Nuclear Magnetic Resonance (NMR) Spectroscopy to understand hepatic lipid metabolism in paediatric NAFLD

What is this study looking at?
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in children and young people (CYP). NAFLD is an overweight/obesity-related condition, but a high body mass index is only one of the factors that determine disease. Certain people are more susceptible to the condition.

This is partially determined by genetics, but other influences are likely to also be important. Studying liver tissue (biopsy) is one such way to examine the processes involved in development of disease. However, it is unpleasant and invasive. Given the risks, inconvenience and limitations of studying liver tissue itself, modern imaging techniques can be utilised to look at processes going on in the cells. Once these processes are understood treatments can be targeted to modify them.This project will look at tiny frozen sections of liver to further evaluate and develop imaging protocols using a technique called nuclear magnetic resonance (NMR) spectroscopy. The study will look specifically at the pattern and the ‘metabolism’ (i.e. uptake, processing and release) of lipids (fats) within the liver cells of a CYP with NAFLD, comparing this with the pattern in their blood and also with liver cells from CYP without NAFLD.

Why is this research important?
NAFLD is estimated to occur in up to 10% of CYP with 3% having evidence of progressive disease. Separating out those who will develop significant liver injury (progressive fibrosis) from those who will not, is not currently possible.This study will be of value for phenotyping (observing biochemical characteristics) of CYP with NAFLD to decide which groups of patients are most suitable for therapeutic intervention. The data will assist the development of biopsy-free evaluation of liver disease and used to inform studies of novel therapies for NAFLD in CYP.

What about the future?
The hope is that this study will lead to the ability to use NMR to evaluate the patterns of lipids in liver cells of patients with NAFLD in a non-invasive and safe way. This project may also yield results which can be used to develop a planned trial of novel treatment in children and young people with NAFLD. This treatment will be aimed at changing the lipid profile and metabolism of the liver to reduce progression of NAFLD.

Professor Alastair Sutcliffe

Bilibaby: an ongoing project to develop a screening test to be able to detect bilirubin in stool to screen for childhood liver diseases

Professor Alastair Sutcliffe at King’s College London

Bilibaby: an ongoing project to develop a screening test to be able to detect bilirubin in stool to screen for childhood liver diseases

What is this study looking at?
This study is looking into ways to identify biliary atresia (BA) in newborns by looking at the stool (poo) of babies born with BA. The researchers have produced a testing stick which can test stool for neonatal cholestasis.

The stick changes colour from colourless to pink when no problem is detected with the stool but remains colourless when there is a problem with bile flow.This funding has been awarded to enable further testing of the stick. Nurses at King’s College London will collect stool samples from all babies with BA over a 6 month period, as well as from other babies to test the accuracy of the stick.

Why is this research important?
At the moment healthcare professionals use their judgement to tell whether or not a stool is a healthy colour or whether it is pale, which could be a warning sign of liver disease. Sometimes this can be difficult as it is a very subjective process.

The stick would allow midwives to test all babies’ stool and would tell midwives whether or not the baby may have a problem with their liver due to a reduced bile flow.

What about the future?
If the study is successful the research team will look to develop and produce the testing stick which will help healthcare professionals to identify diseases such as BA in newborns at an early stage in order to improve the outcome for patients with BA.

Dr Steffen Hartleif

The role of vascular adhesion protein-1 in the pathogenesis of chronic graft hepatitis and fibrosis after paediatric liver transplantation

Dr Steffen Hartleif at Graft Injury Group, Birmingham Children’s Hospital in collaboration with University Hospital Tuebingen

The role of vascular adhesion protein-1 in the pathogenesis of chronic graft hepatitis and fibrosis after paediatric liver transplantation

What is this study looking at?
Patient and graft survival after paediatric liver transplantation (pLT) has improved significantly. However, chronic graft hepatitis and fibrosis are common and account for long-term graft injury and graft loss after pLT. Currently, mechanisms of chronic graft hepatitis and fibrosis are incompletely understood and there is no specific treatment.

In other liver diseases associated with inflammation and fibrosis, the vascular adhesion protein-1 (VAP-1) plays an important role in immune responses that mediate liver injury. This study looks into whether VAP-1 also drives inflammation in chronic graft hepatitis.

Why is this research important?
As survival after paediatric LT has improved, chronic allograft hepatopathy is likely to play an increasingly important role for late morbidity and potentially also for long-term survival. However, the mechanisms of chronic allograft hepatitis and fibrosis after paediatric LT remain largely unclear. This study will contribute to assess a new pathway of alloimmune response after organ transplantation.

If we can confirm an important role for VAP-1 signalling pathways in graft hepatitis and fibrosis, soluble VAP-1 could serve as a novel biomarker. There is great medical need for biomarkers in order to monitor unapparent chronic graft hepatitis and to prevent severe graft fibrosis in children after LT.

What about the future?
If VAP-1 mediated pathways prove to be important in the development of late graft inflammation and fibrosis, there may be recommendations and interest in designing a multicentre study to investigate the possibility of implementing therapeutic strategies in children with progressive fibrosis after pLT.

Dr Gary Reynolds

Lysophospholipid profiling of Fibrolamellar hepatocellular carcinoma (FLHCC) and identification of novel therapeutic targets

Dr Gary Reynolds at Queen Elizabeth Hospital Birmingham

Lysophospholipid profiling of Fibrolamellar hepatocellular carcinoma (FLHCC) and identification of novel therapeutic targets

This research is co-funded by BSPGHAN and Children’s Liver Disease Foundation (CLDF)

What is this study looking at?
Fibrolamellar hepatocellular carcinoma is a liver cancer that affects adolescents. Bio-active lipids (fat-like substances) are key molecules in the blood and cells for normal development and function that can become unbalanced leading to similar effects in cancer. This research will target one of these groups of bio-active lipids (lysophospholipids) to understand more about the tumours biology and identify potential drug treatments.

Why is this research important?
Fibrolamellar hepatocellular carcinoma is a very rare type of primary liver cancer and therefore very little is known about it. There are no proven or effective treatment options other than radical surgery or transplantation. Because of this and as it is usually discovered at a late stage, the option of surgery or transplant is only possible for 70% of patients and recurrence of the cancer as well as treatment is a big problem.

What about the future?
The results from this study will provide much needed information into this cancer and data for a more substantial grant, moving towards clinical trials for new future treatments.

Dr Vandana Jain

Association of stool microbial profile with short-term outcome in infants with biliary atresia after Kasai Portoenterostomy

Dr Vandana Jain at King’s College Hospital, London

Association of stool microbial profile with short-term outcome in infants with biliary atresia after Kasai Portoenterostomy

What is this study looking at?
Biliary atresia (BA) is a disease in children where inflammation within the bile ducts lead to jaundice and liver inflammation. An operation called a “Kasai-Portoenterostomy” (Kasai) can be performed in the first two months of life to “re-plumb” the liver to the gut to restore bile flow between the liver and the gut.It is thought that microorganisms (such as bacteria, viruses, and fungi) within the gut may have an impact on how serious liver disease in children with BA becomes.

The research team will look at the microorganisms inside the guts of children who have had the Kasai at different ages.The team will then compare which microorganisms are present in the guts of children who have BA but are healthy after the Kasai procedure, those with BA who have the procedure but need a liver transplant afterwards and healthy children without biliary atresia.

Why is this research important?
The impact of microorganisms in the gut has been studied in adults with liver disease and is believed to play a role in adult liver disease. Until now there has been little research into its potential role in biliary atresia.

This research will further our knowledge and understanding of whether microorganisms have a role in paediatric liver disease.

What about the future?
It is hoped that we will be able to find out if microorganisms inside the gut play a role in making liver disease worse in biliary atresia, and if so, which ones.

If microorganisms are identified the next step is to find out how to target these bacteria so we can reduce the number of harmful bacteria in the guts of biliary atresia patients. Potential treatments may include antibiotics, diet or probiotics.

I even met a young lady called Katie who has the same condition as Ollie. She was amazing at answering any question I had on my mind. This meant a lot to me as Alagilles is such a rare condition.“Ollie is doing pretty well at the moment although the itching (one of the symptoms of his condition) can really upset him. It’s one of the reasons I am so pleased to speak to people who understand what this is like.

I have kept in touch with Katie since the weekend and I also swapped numbers with some of the other mums. It is so helpful for me just to speak about what we’re going through with people who are expericing a similar situation. I wouldn’t be able to do this if we hadn’t gone to the family weekend and now I have a little support network.”

Dr Ivana Carey

New non-invasive serological and virological markers of hepatitis b virus (HBV) – can they help determine future chronic hepatitis b outcomes in children with perinatally acquired HBV infection?

Dr Ivana Carey at King’s College Hospital

New non-invasive serological and virological markers of hepatitis b virus (HBV) – can they help determine future chronic hepatitis b outcomes in children with perinatally acquired HBV infection?

What is this study looking at?
Although the recently introduced general HBV vaccination in infancy, efficient screening during pregnancy and adequate management of pregnant HBV positive parents reduces the risk of transmission to the child there still remains a large cohort of paediatric patients contracting this persistent disease.

This study is focusing on the impact of HBV infection on liver disease progression and looking into its management to reduce progression to prevent further transmission.This study is investigating the new markers of HBV proteins (antigens) to monitor paediatric patients with chronic hepatitis b and whether this can predict the progression of liver disease in adolescence or young adulthood.

Translating genetic information of the virus into HBV proteins (antigens) were recently discovered and represent very useful non-invasive tool to monitor activity of HBV in blood without needing the liver sample.

The study aims to explore whether any of these markers of viral activity at diagnosis alone or in combination help to predict liver disease progression through enabling more precise diagnostics and whether this can assist in early intervention.

Why is this research important?
Chronic hepatitis b accounts for 1 million deaths yearly and it is a persistent disease contracted in childhood. Despite vaccination, passive immunisation and HBV treatment in pregnancy, 10% of infants of mothers with high viral load still get infected. Understanding the pathways involved in the viral control in children is important to prevent the progression of the disease and reduce the risk of having highly active disease during childbearing age.

What about the future?
If this study is successful it will lead to considering the setup of a national multicentre study focusing on this cohort of patients and their long-term management. This will have a further impact on reducing the risk of transmission and disease burden overall.

Professor Amin Rostami and Dr Jill Barber

Optimising drug regimens in paediatric liver disease using experimentally-derived simulation tools

Professor Amin Rostami and Dr Jill Barber at the University of Manchester

Optimising drug regimens in paediatric liver disease using experimentally-derived simulation tools

What is this study looking at?
This research is exploring how medications act in children’s livers including those which a liver disease. Livers vary from person to person and these differences can affect how much of a drug a child should be given. Size of liver is one important variation and another is the level of different enzymes in the liver.

The enzymes help different reactions take place in the liver including the breakdown of medications. The research team have developed a way to measure the level of enzymes in livers. They will be looking at livers from children with and without liver disease and comparing the levels of a number of different enzymes.

Why is this research important?
At the moment it is very difficult for doctors to know exactly how much of a drug a child should be given. This means they have to try and estimate dosages based on adult amounts.

What about the future?
The results of this study will feed into a model which will help doctors prescribing medicines to children with liver disease to prescribe the most suitable dose.

Professor Deborah Gill

In vivo liver genome editing for the treatment of Alpha-1 antitrypsin deficiency

Professor Deborah Gill at John Radcliffe Hospital, University of Oxford

In vivo liver genome editing for the treatment of Alpha-1 antitrypsin deficiency

This research is co-funded by BSPGHAN and Children’s Liver Disease Foundation (CLDF)

What is this study looking at?
Gene therapy holds the promise of a curative treatment for genetic diseases by delivering a functional copy of a gene into cells to compensate for non-functional (defective) versions. This is called ‘gene addition’. However, the liver grows in paediatric patients, which means that the gene addition approach may only have a short-term impact. This study is proposing a new strategy called genome editing to precisely insert a functional copy of the gene into the genome (complete set of genes or genetic material present in a cell or organism) of the patient’s liver cells, so that it could continue to function for the life-time of the patient.It will test the genome editing strategy on a mouse model of alpha-1 antitrypsin (A1AT) deficiency, in the hope it will replicate findings of tests with liver cells grown in culture and artificial ‘mini livers’ (organoids). The study hopes to evaluate the safety and therapeutic applicability before clinical trials can begin.

Why is this research important?
There is currently no definitive cure for AAT deficiency, however, genome editing provides an opportunity to address this unmet need. While this study focuses on AAT deficiency, it hopes to open the platform for exploration of other genetic liver diseases where genome editing may be beneficial.

What about the future?
If the strategy is successful in demonstrating genome editing of the A1AT gene in mice, the results will help progress this approach for clinical development. These results will also support further funding applications to use this approach for the treatment of other genetic liver diseases.

Dr Luke Boulter

Using single cell sequencing to determine how bile ducts form: understanding the mechanisms to fight Biliary Atresia

Dr Luke Boulter at the Institute of Genetics and Molecular Medicine, Edinburgh

Using single cell sequencing to determine how bile ducts form: understanding the mechanisms to fight Biliary Atresia

This research is co-funded by BSPGHAN and Children’s Liver Disease Foundation (CLDF)

What is this study looking at?
Bile ducts (tubes that carry bile from the liver in to the intestine) fail to form normally in biliary atresia and currently, children require surgery or liver transplantation as treatment. What we don’t understand is how normally bile ducts form when the liver grows in the foetus.

Understanding this process will be essential for understanding what goes wrong in biliary atresia. A mouse mutant has been developed where biliary cells form in the foetal liver but then fail to form bile ducts. This research aims to investigate what factors cause biliary cells to form ducts in the foetal liver and ask how these factors change in our mutant mouse model of biliary atresia.

Why is this research important?
The process by which the ductal plate (cells that make up the building blocks for bile ducts) changes into a bile duct is unclear. By understanding the processes by which bile ducts form will help to identify the causes of biliary atresia leading to development of therapies to stimulate growth and repair the bile duct.

What about the future?
The aim of this preliminary study is to provide data to contribute to a subsequent larger research grant proposal and support applications for greater levels of funding to investigate further.