Liver Regeneration: the Role of Bioengineering (2011)

considerably reduced the incidence of chronic carriers and viral induced cirrhosis(5).However, close to 20% of the livers transplanted in the USA and 30% in Europe have a preventable underlying cause, alcoholic liver disease.Furthermore, approximately 45% of deaths due to liver cirrhosis in the USA are associated with alcohol abuse (1,3,4).Patients with pathologies like hepatic cancer, congenital malformations and metabolic diseases, and acute hepatic necrosis make up the remaining percentage of the list.The success of liver transplantation has resulted in a progressively increasing demand for such treatment.Nevertheless and as mentioned above, the availability of donor organs has remained stable, resulting in the number of potential recipients far exceeding organ supply.Due to this, several strategies have been explored in the past decade or so with the aim to increase access to liver transplantation.These consist of obtaining organs from non-heartbeating and live donors; and/or using split liver technique and livers from expanded donor criteria.In addition, the introduction of the Model for End-Stage Liver Disease (MELD) score system implemented on February 27 of 2002 in the United States tremendously helped Organ Procurement Organizations to prioritize patients waiting for a liver transplant.The MELD score is a numerical scale used for adult liver transplant candidates that ranges between 6 (less ill) and 40 (gravely ill).The number is calculated using the most recent laboratory tests for bilirubin, INR and creatinine( 6) and the individual score determines how urgently a patient needs a liver transplant within the next 3 months.The implementation of more adequate and efficient allocation systems, development of better immunosupressive regimens, and the increase of living donors have all helped to raise overall patient survival and graft survival in the past decade in the United States.The number of transplanted livers also increased to an all time high in 2006, with a marked decrease on the waiting time for liver transplantation after MELD score system implementation, especially for the sickest patients.The best example of the impact of these measures is the increase of 6% (86% in 2007) and 16% (87% in 2007) of the unadjusted 1-year graft survival for deceased donor and living donor liver recipients between 1998 and 2007, respectively.This explains also the improvement of 3% (89% in 2007) and 11% (91% in 2007) of the unadjusted 1-year patient survival for deceased donor and living donor liver recipients for the same period, respectively(7).However, these numbers decrease significantly when we consider 5-year patient survival, showing how much remains to be done.In 2007 it was 74% and 79% for deceased donor and living donor liver recipients, respectively.These numbers decrease even further for the 10-year patient survival, where in 2007 there were 61% and 71% patient survival for deceased donor and living donor liver recipients, respectively.One important note is that patient survival was higher than graft survival ~5%, due to the opportunity for repeated liver transplantation in the event of graft failure(8).These numbers highlight the need for innovative therapies that can increase patient survival, as well as lower costs to the health care systems.Naturally acquired tolerance research and its experimental clinical induction is a good example of this.The identification of molecular signatures in naturally tolerant patients to whom immunosuppression could be stopped, and of tolerance induction, through lymphocyte depletion or T lymphocyte costimulation blockade, are some of the most advanced approaches to decrease the complications of immunosuppression(9). Additionally, artificial liver devices which can efficiently remove accumulated lethal toxins f r o m b l o o d o r p l a s m a b y u s i n g m e m b r a n e f i l t r a t i o n a n d / o r a d s o r b e n t s h a v e b e e n developed as support devices.Liver Dialysis Device, Molecular