Pathways of psychosocial factors, stress, and health outcomes after liver transplantation.

The impact of stress and individual factors on health outcomes in general medicine and transplantation are well documented. Few researchers have investigated the complex relationships between these constructs. This longitudinal study assessed coping style, self-regulatory ability, hostility, and social support at baseline among a cohort of 130 adult liver transplant recipients at the Starzl Transplant Institute, University of Pittsburgh Medical Center, and followed those subjects with interview and medical records data about personal and transplant-related stress, physical and mental health outcomes throughout the first post-transplant year. Results show a number of strong bidirectional relationships between coping style, self-regulatory ability, hostility, the caregiver relationship and family environment, personal and transplant-related stress over the second half of the first post-transplant year, and health (especially mental) outcomes at 12 months post-transplant. Stress mediates the relationship between psychosocial factors and mental health outcomes. The importance of those relationships to researchers and clinicians is discussed.

One thousand consecutive primary liver transplants under tacrolimus immunosuppression: a 17- to 20-year longitudinal follow-up.

BACKGROUND: Tacrolimus has proven to be a potent immunosuppressive agent in orthotopic liver transplantation (OLT). The aim of this study is to examine its long-term efficacy and safety. METHODS AND RESULTS: One thousand consecutive primary OLTs performed between August 1989 and December 1992 and maintained under tacrolimus-based immunosuppression were followed up until January 2009. Patient and graft survivals with corresponding causes of death and retransplantation, maintenance immunosuppression, and adverse effects were examined. The study population includes 600 males and 400 females comprising 166 children, 630 adults, and 204 seniors. The mean follow-up was 17.83 (range, 16.1-19.50) years. The overall 20-year actuarial patient and graft survivals were 35.8% and 32.6%, respectively. At the last follow-up, 442 patients were alive; 133 (77.1%) children, 265 (34.5%) adults, and 44 (16.1%) seniors (P=0.0001). After the first post-OLT year, cardiopulmonary events, recurrence of primary disease, and malignancy were the main causes of death. Overall, 183 recipients underwent retransplants; mainly for primary nonfunction, hepatic artery thrombosis, and recurrent primary disease, 180 required dialysis, and 45 underwent kidney transplant. A total of 97.7% of the survivors were on tacrolimus and 26.2% were also receiving adjunctive immunosuppressants at the last follow-up. CONCLUSIONS: The overall 20-year actuarial patient and graft survivals were 35.8% and 32.6%, respectively, with significantly better survival among children. Age-related complications, recurrence of primary disease, and malignancy were the major causes of late graft loss. Graft loss related to immunologic reasons was rare. The prevention of recurrent disease and newer immunosuppressive regimen will further improve these results.

Spontaneous bacterial peritonitis before liver transplantation does not affect patient survival.

BACKGROUND & AIMS: Spontaneous bacterial peritonitis (SBP) is a devastating complication of cirrhosis with high mortality. The impact of a prior episode of SBP on the outcome of liver transplantation (LT) is not well known. We aimed to determine the short- and long-term morbidity and mortality of patients who received LT, with and without a history of SBP. METHODS: We reviewed the records of all adult patients who underwent LT at a single center between June 1999 and June 2009. Patients with SBP were compared with all other patients who underwent LT during the same time period, without prior episodes of SBP. RESULTS: A total of 1491 adult patients underwent LT in the study period; 80 (5.4%) had at least 1 episode of SBP before LT. The mean follow-up time for all patients in the study was just over 4 years. Patients in the SBP cohort were more likely to be male (74%) and to have alcoholic liver disease. Patients with SBP had higher Child-Pugh and model for end-stage liver disease scores at the time of transplantation compared with controls, but there was no difference in long-term mortality between the 2 groups. Patients with SBP, however, were more likely to require surgery for complications related to LT within 1 year and were more likely to die of sepsis. CONCLUSIONS: Despite higher Child-Pugh and model for end-stage liver disease score at the time of LT, survival times of patients with SBP before LT are similar to those patients without SBP.

Recurrent disease following liver transplantation for nonalcoholic steatohepatitis cirrhosis.

Recurrence of the original disease following liver transplantation is not uncommon and can lead to graft failure. There are limited data on recurrent fatty liver disease following liver transplantation. The aim of this study was to determine the incidence of recurrent fatty liver disease in patients with biopsy-proven nonalcoholic steatohepatitis, its effect on survival, and whether there are any predictive factors for recurrence. We analyzed patients undergoing liver transplantation for nonalcoholic steatohepatitis cirrhosis from 1997 to 2008 at a single center. Patients undergoing transplantation for cholestatic disease, alcohol, hepatitis C, or cryptogenic cirrhosis were controls. Ninety-eight patients underwent transplantation for nonalcoholic steatohepatitis cirrhosis. Recurrent fatty liver disease was seen in 70%, 25% had recurrent nonalcoholic steatohepatitis, and 18% had stage II/IV or greater fibrosis at a mean of 18 months. No patients with recurrent nonalcoholic steatohepatitis developed graft failure or required retransplantation at a follow-up of 3 years. No recipient or donor factors were associated with disease recurrence, although patients with recurrent nonalcoholic steatohepatitis had a higher incidence of diabetes, weight gain, and dyslipidemia at the time of diagnosis of recurrence. One-third of patients with recurrent nonalcoholic steatohepatitis had normal liver enzymes at the time of diagnosis post-transplantation. In conclusion, recurrent fatty liver disease is common following liver transplantation for nonalcoholic steatohepatitis cirrhosis but does not lead to early allograft failure. Recurrent nonalcoholic steatohepatitis can occur despite normal liver enzymes, and features of metabolic syndrome are associated with disease recurrence.

The grateful dead: damage-associated molecular pattern molecules and reduction/oxidation regulate immunity.

The response to pathogens and damage in plants and animals involves a series of carefully orchestrated, highly evolved, molecular mechanisms resulting in pathogen resistance and wound healing. In metazoans, damage- or pathogen-associated molecular pattern molecules (DAMPs, PAMPs) execute precise intracellular tasks and are also able to exert disparate functions when released into the extracellular space. The emergent consequence for both inflammation and wound healing of the abnormal extracellular persistence of these factors may underlie many clinical disorders. DAMPs/PAMPs are recognized by hereditable receptors including the Toll-like receptors, the NOD1-like receptors and retinoic-acid-inducible gene I-like receptors, as well as the receptor for advanced glycation end products. These host molecules 'sense' not only pathogens but also misfolded/glycated proteins or exposed hydrophobic portions of molecules, activating intracellular cascades that lead to an inflammatory response. Equally important are means to not only respond to these molecules but also to eradicate them. We have speculated that their destruction through oxidative mechanisms normally exerted by myeloid cells, such as neutrophils and eosinophils, or their persistence in the setting of pathologic extracellular reducing environments, maintained by exuberant necrotic cell death and/or oxidoreductases, represent important molecular means enabling chronic inflammatory states.

First clinical use of a novel bioartificial liver support system (BLSS).

The first clinical use of the Excorp Medical Bioartificial Liver Support System (BLSS) in support of a 41-year-old African-American female with fulminant hepatic failure is described. The BLSS is currently in a Phase I/II safety evaluation at the University of Pittsburgh/UPMC System. Inclusion criteria for the study are patients with acute liver failure, any etiology, presenting with encephalopathy deteriorating beyond Parson's Grade 2. The BLSS consists of a blood pump; a heat exchanger to control blood temperature; an oxygenator to control oxygenation and pH; a bioreactor; and associated pressure and flow alarm systems. Patient liver support is provided by 70-100 g of porcine liver cells housed in the hollow fiber bioreactor. The patient exhibited transient hypotension and thrombocytopenia at initiation of perfusion. The only unanticipated safety event was a lowering of patient glucose level at the onset of perfusion with the BLSS that was treatable with intravenous glucose administration. Moderate changes in blood biochemistries pre- and post perfusion are indicative of liver support being provided by the BLSS. While the initial experience with the BLSS is encouraging, completion of the Phase I/II study is required in order to more fully understand the safety aspects of the BLSS.