Liver disease and cancer

• Introduction
• Work at CRM
• Frequently Asked Questions - Prof Stuart Forbes
• Macrophage Cell Therapy for Liver Cirrhosis

Introduction

Chronic liver disease is the 5th largest cause of death in the UK, and is common worldwide. Chronic damage leads to scarring and eventually cirrhosis which can lead to liver failure and ultimately liver cancer. Although liver transplantation is a cure for severe liver disease there are insufficient numbers of suitable organs. Furthermore liver transplantation results in the need for lifelong immunosuppression. Understanding and improving how the liver regenerates, and developing alternatives to liver transplantation is therefore a priority of our research at the MRC Centre for Regenerative Medicine.

The liver is a highly regenerative organ, which can regrow even after 70% of its volume has been removed. Damage to the liver occurs from many causes including genetic diseases, viral infections, immune mediated diseases, obesity, excessive alcohol intake and drug overdoses. If the damage is too severe then liver failure can occur.

Chronic damage also increases the chance of liver cancers developing. The bile ducts are a network of tubes that drain toxins from the liver. Bile duct cancer – known as cholangiocarcinoma – affects around a 1000 patients a year in the UK. It is often diagnosed at an advanced stage, which makes it very difficult to treat with surgery and cholangiocarcinoma typically does not respond to chemotherapy. Researchers are trying to understand what drives the growth of these cancers so we can develop new treatments.

Work at CRM

• Dr David Hay focuses on generating hepatocytes from embryonic and induced pluripotent stem cells. He has developed a technology to produce large quantities of hepatocytes in a dish, which can be used to develop novel models of drug-induced liver injury and Hepatitis C virus infection. In the long run, these cells might represent a source for supporting failing human liver function. Dr Hay also collaborates with Prof Mark Bradley at the University of Edinburgh’s School of Chemistry. Together they investigate chemical substances such as particular synthetic surfaces that can provide support for stem cells and help them turn into liver cells.
• Prof Stuart Forbes and his team work to understand the role of liver progenitor cells (HPCs) in the damaged liver. They aim to identify the signals that control the repair of damaged tissue, which will offer targets for drugs to stimulate healing of the liver. They also study the use of stem cells to repair the liver following transplantation by improving liver regeneration and removing scar tissue.

Frequently Asked Questions - Prof Stuart Forbes

Prof Stuart Forbes introduces his research at the MRC Centre for Regenerative Medicine in the video below.

1. Are you involved in clinical trials?

   Yes. Together with Prof Philip Newsome (Birmingham University) the Forbes lab has developed and undertaken the so-called ‘REALISTIC’ study (REPEATED AUTOLOGOUS INFUSIONS OF STEM CELLS IN CIRRHOSIS): a multicentre, phase II, open label, randomised controlled trial of repeated infusions of autologous CD133+ bone marrow stem cells mobilized by G-CSF in patients with cirrhosis. This trial runs in Edinburgh, Birmingham and Nottingham and has finished recruiting 81 patients. The results of this trial are not known yet as monitoring patients as part of the follow-up phase is ongoing. More information about the trial can be found here.  The trial was registered at Current Controlled Trials on 18 November 2009 (ISRCTN number 91288089, EuDRACT number 2009-010335-41).

2. Are you currently recruiting for other clinical trials?

   The Forbes lab have a new Clinical Trial commencing in 2016. 68-77 patients for this single centre, safety, feasibility and efficacy phase I to phase II study will be recruited locally (Edinburgh area) through the UK's National Health Service (NHS). This study is called 'MATCH 0.1', (Macrophage Therapy for Liver Cirrhosis).

3. Can I take part in a future clinical trial?

   Should the Forbes lab take part in future clinical trials, patients will be recruited locally through the UK’s National Health System (NHS).

4. When will this stem cell based treatment become available?

   Unfortunately there are many research questions still unanswered. Also, the vigorous clinical trial process is strictly regulated to make sure treatments are effective and safe for patients. There are still a number of regulatory hurdles to pass before a treatment becomes available in the clinic. This is quite a long process unfortunately, it can easily take 10-15 years.

5. Can you give me medical advice?

   Unfortunately Prof Stuart Forbes and his team cannot give medical advice or recommend on a specific stem cell therapy or trial. We do recommend you take advice of your local healthcare team.

6. Where can I get more information?

   • Bile Duct Cancer: there is a very good charity called the AMMF Cholangiocarcinoma Charity. They offer support, advice and are well placed to provide you with up-to-date information.
   • Liver disease: the British Liver Trust provides very accurate and balanced information. They also have support groups and can help you find a group near you.
   • Stem cells and clinical trials: please see the Patients section on our website and follow the links.

7. If I can’t take part in a clinical trial, can I help in other ways?

   Yes. Philanthropy in research is increasingly important as funding streams change. It is thanks to people like you that we are able to attract the brightest minds and provide world-class research facilities. If you wish to support the Forbes lab and their research efforts to better understand liver disease and cancer and help develop treatments, you can donate to CRM or to our dedicated ‘Liver and Bile Duct Cancer Fund’. Your contribution and support is much appreciated.