Chronic liver disease is the fifth leading cause of death in the United Kingdom. With the long-standing shortage of donated, transplantable livers, the prognosis of such patients seems grim.
Several preclinical studies in animals have established that mobilization of bone marrow stem cells or direct injection of bone marrow stems into a damaged liver can augment healing and improve survival (Sukaida I, and others, Hepatology 2004;40:1304–11; and Yannaki E, and others, Exp Hematol 2005;33:108–19). Some small clinical trials have examined the use of a patient’s own bone marrow stem cells to prime the liver and stimulate its own internal healing mechanisms. These studies were small and varied in the manner in which the stem cells were delivered, but they di show that the stem cell treatments were safe and even improved the health of the liver significantly (Gordon MY, and others, Stem Cells 2006;24:1822–30; Terai S, and others, Stem Cells 2006;24:2292–8). Also, in patients with liver cancer who had to have portions of their livers removed, bone marrow stem cell treatments accelerated liver healing (am Esch JS, and others, Ann Surg 2012;255:79–85; am Esch JS, and others, Stem Cells 2005;23:463–70; and Furst G, and others, Radiology 2007;243:171–9).
Clearly there is a need for a larger, more systematic study of the efficacy of bone marrow stem cells as a therapeutic agent in patients with liver failure. To that end, Philip Newsome and his colleagues at the University of Birmingham, in collaboration with colleagues from Scotland, Newcastle, and Nottingham have initiated the REALISTIC trial, which stands for REpeated AutoLogous Infusions of STem cells In Cirrhosis.
This is a multi-center clinical trial and it will examine patients with Cirrhosis (fatty liver disease), regardless of the cause of that liver disease. Patients whose livers were damaged by excessive alcohol use, hepatitis B or C infections, or genetic conditions are all eligible for this study, but anyone who liver is too far-gone to be helped by a treatment like this or has had a liver transplant is not eligible.
Patients will receive injections of a drug called lenograstim (G-CSF) to mobilize bone marrow stem cells into the blood. These blood-based stem cells will then be collected and concentrated, and then implanted into the liver. Patients will be assessed at 3 months after the treatment and then followed-up for 1 year. Liver health will be assessed by means of medical imaging of the liver and various blood tests.
Patients will be evaluated using the Model for End-Liver Disease or MELD scoring system. Secondary tests will measure the degree of liver scarring, the degree of liver stiffness, blood tests, survival, and liver function.
Patients will also be placed into three groups. One group will only have the bone marrow stem cells mobilized from bone marrow without being collected. Another group will have the cells collected and implanted into the liver. The third group will receive standard care with not stem cells treatments.
There is a need for a study like this. I only hope that Newsome and his group can recruit the patients and get started collecting data as soon as they can.