EU funds d-LIVER project to help people suffering from liver disease

Published on June 5, 2013 at 3:51 AM

The EU has provided funding for the d-LIVER project, in which researchers from several countries will work on a number of measures to help people suffering from liver disease. The patients will be offered technology that can monitor and manage their condition at home. The project will also construct a system that will help patients within this chronically ill group to undergo artificial liver support treatment when their own livers are compromised or incapable.

Complex organ
The liver is not just a 'rubbish cleaner', but a central, complex organ that is vital for major parts of the body's biochemistry, and is used by our metabolism and for protein synthesis. Because of this complexity, no one has ever managed to create an artificial, synthetic liver. Quite simply, it is too difficult to find a good replacement for all the functions performed by the liver.

When the liver fails, a patient's body becomes poisoned. If the liver failure is acute, it may be only a few hours before it develops into a life-threatening condition that affects all the cells in the body. Not even the brain will be able to function optimally. Many patients suffering from liver failure find that a liver transplant is their only treatment option, but only one in twenty receive this, because of a lack of donors.

Financial burden of treatment
Chronically ill patients need intensive monitoring, treatment and also periodic stays in hospital. They often have a poor quality of life, because it is difficult to have this kind of illness and have a job at the same time.
Special skills are required to monitor patients with liver failure, since they have complex clinical symptoms, including abnormal blood parameter values. Their medical monitoring therefore requires them to have access to specialists. Patient treatment places a high financial burden on society, and this is one of the things that the d-LIVER project aims to improve.

Blood circulated through artificial liver
Instead of an artificial liver within the body, the researchers are now developing an artificial liver unit outside the body. Cells from humans or pigs live and grow in it - and function as real liver cells. The cells grow in a three-dimensional structure in a reactor that functions like an 'incubator'. It ensures that the conditions are right for the liver cells to function properly. The reactor must be able to control temperature and to circulate nutrients and oxygen in the right quantities to all the cells.

The artificial liver will be able to act as an 'auxiliary engine' for a patient, during periods when the patient's own liver cannot manage to function adequately. Blood is recirculated from the patient through the artificial liver - a process that takes several hours. In order to avoid the problem of rejected cells, every single patient needs a bio-reactor. This means that meticulous planning and preparations are required for every patient.
'We envisage that it will be possible for this type of artificial liver to be used for patients with extremely poor liver function, preferably before the patients become so ill that their brain function is affected and they cannot manage to look after themselves,' says Frode Strisland of SINTEF. Patients undergo crisis periods when their liver function is insufficient, resulting in a build-up of waste products in the body. This tends to happen when the patients are suffering from infections or colds - conditions that a healthy liver has plenty of capacity to handle. For liver patients, treatment with an artificial liver can be live-saving until they have recovered, and their own liver capacity becomes sufficient to keep the body going.

'What is very clear is that the new artificial livers will probably have to be operated and maintained in a hospital environment, although the research project will also look at what would be required in order to be able to offer this kind of treatment in a patient's home,' says Strisland.

Prevention is just as important
If we can manage to detect when a liver patient is beginning to have problems, it may be possible to prevent these problems in an early phase, by adjusting their medical treatment. This is cheaper and easier for the health services, and much better for the patient, giving them a chance to avoid the worst crises. For this reason, it is important to pick up on the first signs that a liver is not functioning properly.

It is here - in the preventative part of d-LIVER - that the Norwegian researchers at SINTEF ICT are concentrating their efforts. The idea is to make it possible to supervise patients with liver problems and monitor them at home.
'Monitoring at home should be able to detect patients who are starting to have problems. We think that this may reduce the need for hospital admissions,' says Frode Strisland.

Since the balance of the liver is fundamentally linked to infections and a compromised immune system, the researchers will be developing sensors that patients can wear, that will provide information about physical condition and activity. The project will also create a blood analysis instrument that will measure selected blood parameters on a daily basis. 'This will enable these patients to be monitored significantly better than they are now, when many of them might only get to see a doctor every three months,' says Strisland.

Source: SINTEF

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Next Regeneration: Artificial Livers May Soon Be Ready For Transplant

The ability to generate artificial liver tissue for transplant is within science's grasp, researchers report.

By Matthew Mientka | Jun 01, 2013 09:12 PM EDT

Long have researchers been tantalized by the promise of generating artificial liver tissue for transplantation.

Unlike other organs, the liver can regenerate itself when part is removed -- but only within the body. Once taken from the body, mature liver cells known as hepatocytes quickly lose their ability to function. "It's a paradox because we know liver cells are capable of growing, but somehow we can't get them to grow" outside the body, Sangeeta Bhatia, an engineer at MIT, told reporters.

Bhatia, a professor of health sciences and technology and electrical engineering and computer science, is a senior associate member of the Broad Institute, which focuses on the molecular underpinnings of disease, as well as a member of the university's Koch Institute for Integrative Cancer Research, and Institute for Medical Engineering and Science. On Sunday, Bhatia and her colleagues published a paper in Nature Chemical Biology, reporting the identification of a dozen chemical compounds that help liver cells not only maintain normal function while grown in the laboratory but also to produce new tissue.

Such a breakthrough may help researchers develp engineered tissue to treat people suffering from chronic liver diseases such as hepatitis C -- approximately one of every 14 people on the planet.

A relatively complex organ, the liver serves some 500 functions, divided into four general categories, including drug detoxification, energy metabolism, protein synthesis, and bil production. David Thomas, an associate researcher at the Broad Institute, measured expression levels of 83 liver enyzmes representing some of the trickiest functions for the liver to maintain. After screening thousands of hepatocytes from eight different tissue donors, the investigators identified a dozen compounds that help the cells maintain those functions, helped to regenerate cells, or both. They managed to adapt the system so that liver cells grew, in layers with the fibroblast cells, in small depressions in a lab dish, allowing researchers to rapidly study how 12,500 different chemicals affect hepatocyte function and regeneration.

When two of the compounds appeared to work especially well in cells from younger donors, investigators then tested them in liver cells generated from induced pluripotent stem cells. Though previous attempts with such stem cells had failed to generate mature liver cells, the compounds got the job done. Bhatia and her colleagues now wonder whether the compounds might work to help mature other types of cells, too. As other scientists investigate that question, the MIT team plans next to embed the treated liver cells on scaffolds of polymer tissue for implantation into mice, to test whether they might be suitable for liver tissue transplants. They also plan to investigate whether they can use the compounds to develop drugs that would help regenerate liver tissue within the body, without a trasplant operation.

The MIT researchers collaborated with scientists at Harvard University and the University of Wisconsin on the project, which received funding from the National Institutes of Health.

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