**4. Future perspectives**

184 Liver Regenaration

OLT is accessible to patients in all levels of society. Successful OLT has been reported in Down Syndrome patients and in drug abusers. Adequate preparation by medical, paramedical, and clinical coordinator teams is of utmost importance in complicated clinical

Chronic biliary infection is frequent in Caroli disease, primary sclerosing cholangitis, and secondary sclerosing cholangitis. Because the infection is usually confined to the liver, outcome of OLT is excellent as transplantation removes the source of the infection. OLT is

The Model for End-Stage Liver Disease (MELD) scoring system aims to reduce liver waitlist mortality by transplanting sicker patients more rapidly. Abstinent alcoholics frequently belong to the sickest patient groups. Nowadays, OLT is a very good indication in such patients if the recipient remains abstinent and is compliant. If the recipient remains abstinent, alcoholic cirrhosis is one of the best indications for OLT as this is the only disease that does not recur in the allograft. Moreover, abstinent alcoholics that receive OLT offer a unique opportunity to study the effect of immunosuppression withdrawal without primary

Many transplant recipients have undergone previous abdominal and right upper quadrant surgery. These interventions can compromise the transplant procedure. Thus, exploratory or staging laparotomies as well as unnecessary cholecystectomies and cyst fenestrations should be avoided in future OLT patients. Interventional radiology procedures such as the Transjugular Intrahepatic Portosystemic Shunt (TIPSS) are preferred in potential OLT recipients instead of portal hypertension surgery. In cases where portal hypertension surgery cannot be avoided, meso-caval or spleno-renal shunts are the preferred options

HIV patients that are well controlled on Highly Active Antiretroviral Therapy (HAART) are generally not contraindicated for OLT. The indication for OLT relates more so to concomitant HCV and/or HBV infection. Co-infected patients are at higher post-OLT infectious risk. Particular attention should be given to the interaction between anti-viral

especially valuable in these patients as it dramatically improves their quality of life.

**3.2.2 Advanced liver disease in abstinent alcoholic patients** 

**3.1.10 Inability to accept or understand the procedure** 

scenarios.

**3.2 Relative contraindications** 

**3.2.1 Intra-hepatic or biliary sepsis** 

disease involvement in the allograft.

**3.2.3 Previous abdominal surgery** 

leaving the hilar region intact.

drugs and calcineurin inhibitors.

**3.2.5 Positive HBsAg status** 

**3.2.4 HIV infection** 

See above.

Criteria for placement on the waiting list have become more quantitative. Continuous refinement of the allocation system will improve the management of the waiting list (Metsellaar, 2011).

Alternative techniques such as split liver transplantation (SLT) and living donor liver transplantation (LDLT) will allow for expansion of the allograft pools. The bipartition of the liver is especially important in pediatric patients for whom size-matched whole liver allografts are scarce. Split grafts have been associated with reduction in the risk of death on the pediatric waiting list. However, SLT is much less successful in the adult-adult SLT. Donor selection for splitting and technical and logistical expertise to decrease total ischemia time are important factors in successful transplantation. A better understanding of the liver anatomy and improving surgical skills have allowed living liver donation to become a routine procedure in some centers. Given the major risks of the operation required for the donor, whether this procedure will ever find wide application is unclear.

As there will always be more potential recipients than donors, many researchers are working in the field of artificial tissue engineering and regenerative medicine (RM) (Orlando, 2011a, 2011b, 2011c, 2011d, 2012a, 2012b, 2012c). RM holds the promise of regenerating tissues and organs by either stimulating previously irreparable tissues to heal themselves, by treating liver disease with cell therapies, or by manufacturing tissues *ex vivo* using extracellular matrix (ECM) scaffolds.

This last approach, uses ECM scaffolds that have an intact but decellularized vascular network that is repopulated with autologous or allogeneic stem cells and/or adult cells. Liver ECM scaffolds may be produced from humans or animals. In the latter case, human cells are used to repopulate a scaffold of animal origin, coining a new concept called semi-xenotransplantation (Orlando, 2011a, 2011b). Importantly, preemptive transplantation with regenerated tissues will improve outcomes, especially in cases of metabolic and cystic liver disease.

Future progress in the medical treatment of oncology will enhance outcomes in OLT (Lerut, 2007, 2011; Bonaccorsi-Riani, 2010, Foss, 2011). As treatments of vascular tumors, advanced hepatocellular cancer, cholangiocellular cancer, neuroendocrine tumors, and colorectal liver metastases improve, indications for OLT in the 21st century will become more inclusive of advanced oncologic disease states.

Combined organ transplantation is becoming more frequent as many liver diseases are accompanied by renal function impairment. Nowadays, 15% of all liver recipients have combined liver-kidney transplantation.

Transplant teams should focus more on late morbidity and mortality. Currently, the majority of long-term survivors die from infectious disease, cardiovascular disease, or cancer while having a functional graft. This mortality is directly related to the strength of the maintenance immunosuppression. Minimization or even withdrawal of immunosuppressive protocols must become a priority in organ transplantation (Lerut, 2003, 2008). Unfortunately, tolerance protocols are frequently based on a trial and error approach, as good markers to predict tolerance are not yet available (Lerut, 2006). As the liver is an immunoprivileged organ with relatively high resistance against immune responses, liver recipients should be at the forefront of this research.

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