**6. Future directions**

Hepatocyte transplantation has been studied predominantly in patients with chronic metabolic disorders. There is evidence, however, that partial liver engraftment is possible and there may be improvement in neurological status, as noted in small groups of patients with ALF who have undergone hepatocyte transplantation (Bilir et al., 2000; Habibullah et al., 1994; Strom et al., 1997). Xenotransplantation is an intriguing concept and porcine livers have been used for ex vivo perfusion but in vivo use has not yet proven effective due to problems with transspecies rejection. Bioartificial livers and extracorporeal liver assist devices (ELAD) have been used to bridge patients to transplantation and have demonstrated improved neurologic outcomes. There are two cell-based devices. One uses porcine hepatocytes and did not show survival advantage in one large multicenter study and another uses hepatoblastoma cells which was noted to decrease severity of encephalopathy without change in survival in one study (Demetriou et al., 2004; Ellis et al., 1996). Non-biological systems also exist such as albumin dialysis (MARS) and plasmapheresis, and no survival advantage was found on meta-analysis (Khuroo et al., 2004).

## **7. Conclusion**

264 Liver Transplantation – Basic Issues

59 years), so age may have influenced results. More ALF patients were employed or were in full-time education (50 vs. 26.5%). The mental health scores were slightly lower for those who had ALF (68 vs. 79; p=0.022), which was attributed to the fact that the ALF recipients did not undergo typical preoperative education and psychological support prior to OLT. There was no significant difference in parasuicide quality of life scores between the two

ALF patients scored slightly lower in the physical function and role emotion areas compared to normal values, but the values were similar to those who were transplanted for chronic liver disease (Sargent et al., 2006). When more carefully interviewed, six ALF recipients described significant physical inactivity and fatigue for the first 3-6 months following OLT due to weight loss and loss of muscle tone. They also noted a health transition lasting between 3-6 months, during which time dependence on others was present. Pretransplant lifestyles were changed in order to regain independence. Support groups or role models were deemed extremely helpful in coping with the ordeal. The majority felt that they had been given a "second chance at life" and were willing to

Following spontaneous recovery, ALF patients with psychiatric illness who had taken a deliberate APAP overdose are at risk of repeated overdoses. Risk of repeated overdose appears to be less common; however, if the patient was transplanted, perhaps due to the intensity of postoperative care. In two series from the United Kingdom, APAP-ALF patients who underwent OLT showed similar long-term survival (median 5 years and 9 years) compared with patients transplanted for chronic liver disease (Cooper et al., 2009; Karvellas et al., 2010). Less than 5% of those transplanted for APAP overdose reattempted overdose. There was worse 30-day mortality for the APAP-ALF patients, and a greater probability of post-OLT medical nonadherence and adverse events in those who had taken APAP for deliberate self-harm compared with both non-APAP-ALF patients and chronic liver disease

Hepatocyte transplantation has been studied predominantly in patients with chronic metabolic disorders. There is evidence, however, that partial liver engraftment is possible and there may be improvement in neurological status, as noted in small groups of patients with ALF who have undergone hepatocyte transplantation (Bilir et al., 2000; Habibullah et al., 1994; Strom et al., 1997). Xenotransplantation is an intriguing concept and porcine livers have been used for ex vivo perfusion but in vivo use has not yet proven effective due to problems with transspecies rejection. Bioartificial livers and extracorporeal liver assist devices (ELAD) have been used to bridge patients to transplantation and have demonstrated improved neurologic outcomes. There are two cell-based devices. One uses porcine hepatocytes and did not show survival advantage in one large multicenter study and another uses hepatoblastoma cells which was noted to decrease severity of encephalopathy without change in survival in one study (Demetriou et al., 2004; Ellis et al., 1996). Non-biological systems also exist such as albumin dialysis (MARS) and plasmapheresis, and no survival advantage was found on meta-analysis (Khuroo et al.,

reciprocate support to other going through the same process (Sargent et al., 2007).

groups (Sargent et al., 2006).

patients (Cooper et al., 2009).

**6. Future directions** 

2004).

Many advances have occurred that have significantly improved outcomes following transplantation for ALF. Prognostic models are helpful, but they are not entirely predictive of which individuals need OLT and which will survive without OLT. In the setting of organ shortage, alternatives to conventional OLT are being increasingly used, including living donor split grafts, ABO incompatible grafts, and auxiliary grafts, with variable outcomes. The risks and benefits to both the donor and the recipient must be considered. Long term outcomes and quality of life for both donors and recipients are good but prolonged monitoring may be helpful to identify those in distress. Newer technologies are being developed and enhanced to improve short term and long term survival after acute liver injury.
