The liver is a complex organ that fulfills numerous vital functions. Therefore, liver failure is life threatening. It can either be acute or chronic. In both cases liver transplantation is usually the only curative therapy option. However, the number of liver patients is much greater than the number of donor livers available. The treatment with an artificial liver is conceivable as an alternative to transplantation or while waiting for a new organ. It would not cure the patients directly, but the burden on the liver would be reduced and the organ would have the chance to recover.
In addition, the artificial liver can be implemented if liver transplantation is contraindicated e.g. in case of liver resection in patients with malignant tumors. In practice many patients today die as a consequence of liver resection, because without support the liver does not recover quickly enough. Bridging this period with an artificial liver that would temporarily take over important liver functions could in many cases take the burden off the liver, facilitate its recovery, and, thus, save lives.
The already medically approved liver support systems are only geared toward detoxification functions of the liver. However, cell-based systems also assume its synthesis functions. So far, different cell-based artificial liver support systems have been successfully implemented in phase I- and phase II-studies. However, a medically approved cell-based system does not exist. In addition, a modern, telemedically-based disease management platform for the target patient group with chronic liver failure is missing. It would help monitor and support liver substitute therapies at home. Furthermore, indications for liver dialysis sessions could be assessed.
The goal of the project “d-LIVER” is the development of a bio-artificial liver support system, which can be used for continuous but temporary blood purification and liver substitute sessions at the point-of-need e.g. in the hospital or also at the patient’s home. It is essential for the system’s reliable ambulatory use that the support system and especially the patient are monitored during liver dialysis and at home with novel sensors as well as information and communication technology. The project “d-LIVER” uses bioreactors with live liver cells that in contrast to purely technical adsorption and filter techniques fulfill the detoxification and at the same time the synthesis function of the liver.
For this purpose methods of large scale isolation and cultivation are being investigated. Sensors are being developed to monitor the cell’s vitality and functionality in the bioreactor. In addition, a novel information system for the management of liver patients will be developed. It will not only monitor the therapy and patient, but will also model treatment guidelines, will guide doctors and patients through the therapy, and will give real decision support and health advice.
The project “d-LIVER” is very practical and is based on 4 linked and defined scenarios that were developed by clinicians. These scenarios are the basis to determine the specifications for developing communication methods and sensors for the "d-LIVER”-system. Thus, the “d-LIVER”-system will fulfill the demand of continuous clinical support, monitoring, and therapy of liver patients.
These 4 scenarios are:
- Chronic liver failure
- Chronic cholestatic liver disease
- Bridging procedures before liver transplantation
- Acute liver failure
The last scenario will be used at the end of the project for clinical evaluation of the liver substitute system. A whole series of physiological and biochemical parameters will be determined based on these 4 scenarios. They will either be measured in regular intervals or continuously (e.g. monitoring the patient’s health condition, especially liver function) by suitable sensors. Then the parameters will be transferred to the liver patient management system.
The following areas are covered by the system:
- Indication / decision / timing / planning of treatment with the artificial liver
- Basic telemonitoring during liver support therapy
- Evaluation of therapy success after treatment with the artificial liver or after detoxification
- Telemonitoring of the patient liver’s function, of the amount of toxin, and of the general health
- For patients at home: Recommendations on personal lifestyle and behavior based on the sensor data
- Guidance of the doctor and patient through treatments based on therapy plans developed by experts
Aside from the different microsystem-technical sensors, the information and communication technology are a major part of the project. A primary communication path is the telemonitoring of the liver patient. Not only ICT is necessary for this purpose, but also various sensors. For example, portable sensors are being developed to continuously monitor the patient’s health condition at home using many clinically relevant parameters (e.g. heart rate, blood pressure, temperature, activity). Furthermore, the assessment of certain blood parameters is necessary. For this purpose analyzing equipment is being developed that allows a biochemical analysis of liver parameters at the point-of need.
The development foci are the accuracy and the robustness of the assessments. A second communication path is the monitoring of the artificial liver. Novel sensors are being developed for use in the artificial organ to constantly monitor quality and efficiency of the artificial liver’s cells. The third path is the interoperable communication between the artificial liver, the patient sensor network, and the hospital information system. The development of the innovative liver patient management system will lead to a completely new dimension of patient care at home.
The departments of “Telematics & Intelligent Health Systems”, “Biomedical Microsystems”, and “Cell Biology & Applied Virology" of the Fraunhofer IBMT with 13 other partners from Europe are working together on the project “d-LIVER”. It is coordinated by Newcastle University (UK) and cofunded by the EU with 10.9 mio. Euro. The IBMT is head of the task force developing the bio-artificial liver support system and the liver patient management system. The IBMT’s key German partners are the Charité University Medicine Berlin and the firms Stem Cell Systems GmbH and STAR Healthcare Management GmbH.
Further information on d-LIVER: