Deborah Verran

Living donor liver transplantation—Adult donor outcomes: A systematic review

The objective of this study was to evaluate the safety and efficacy of adult‐to‐adult living donor liver transplantation, specifically donor outcomes. A systematic review, with searches of the literature up to January 2004, was undertaken. Two hundred and fourteen studies provided information on donor outcomes. The majority of these were case series studies, although there were also studies comparing living donor liver transplantation with deceased donor liver transplantation. Both underreporting and duplicate reporting is likely to have occurred, and so caution is required in interpretation of these results. Overall reported donor mortality was 12 to 13 in about 6,000 procedures (0.2%) (117 studies). Mortality for right lobe donors to adult recipients is estimated to be 2 to 8 out of 3,800 (0.23 to 0.5%). The donor morbidity rate ranged from 0% to 100% with a median of 16% (131 studies). Biliary complications and infections were the most commonly reported donor morbidities. Nearly all donors had returned to normal function by 3 to 6 months (18 studies). In conclusion, there are small, but real, risks for living liver donors. Due to the short history of adult‐to‐adult living donor liver transplantation, the long‐term risks for donors are unknown. Liver Transpl 12:24–30, 2006.

Chimerism and Tolerance in a Recipient of a Deceased-Donor Liver Transplant

Complete hematopoietic chimerism and tolerance of a liver allograft from a deceased male donor developed in a 9-year-old girl, with no evidence of graft-versus-host disease 17 months after transplantation. The tolerance was preceded by a period of severe hemolysis, reflecting partial chimerism that was refractory to standard therapies. The hemolysis resolved after the gradual withdrawal of all immunosuppressive therapy.

An analysis of late deaths after liver transplantation.

Late deaths (after more than 1 year) after liver transplantation were analyzed in a series of 464 consecutive patients who received liver grafts between 1982 and 1993. Recipients who survived the first posttransplant year (n = 365) had actuarial 5- and 10-year survival rates of 92% and 84%, respectively. Thirty-five patients died between 1.1 and 7.6 years after transplantation (mean, 3.2 +/- 1.9 years). The most common causes of death were related to immunosuppression (40%), namely, chronic rejection, opportunistic infection, and lymphoma. The second most common causes of death were related to the primary disease for which liver transplantation was performed (34.3%), mainly recurrence of hepatobiliary malignancy and hepatitis B. Eight patients (22.9%) died of unrelated and unpredicted causes, most commonly of cardiovascular disease. Although the survival of liver recipients who live beyond the first posttransplant year is excellent, control of rejection and the consequences of chronic immunosuppression are continual threats. Modification of immunosuppression may help in decreasing the mortality of long-term survivors. In addition, better selection of recipients and effective adjuvant therapies (antiviral and antineoplastic) are needed in patients in whom the primary liver disease is notorious for recurrence.

Grade of deceased donor liver macrovesicular steatosis impacts graft and recipient outcomes more than the Donor Risk Index.

Background and Aim:  Donor liver steatosis can impact on liver allograft outcomes. The aim of the present study was to comprehensively report on the impact of type and grade of donor steatosis, as well as donor and recipient factors, including the reported Donor Risk Index (DRI), on liver allograft outcomes.

Central pontine myelinolysis and cyclosporine neurotoxicity following liver transplantation

In a recent series of 44 liver transplants we identified both extrapontine myelinolysis (EPM) - characteristic of cyclosporine neurotoxicity - and central pontine myelinolysis (CPM) in 5 recipients posttransplant. An additional 2 recipients had EPM only posttransplant. MRIs performed in 4 asymptomatic recipients were normal. Large perioperative shifts in serum sodium, hypomagnesemia, and high cyclosporine levels may play a role in the development of these lesions, although the evidence from this study is inconclusive. In addition to supportive care, dilantin was started in patients who had seizures; aggressive magnesium replacement was initiated for hypomagnesemia, and cyclosporine levels were reduced in all patients. All patients demonstrated a slow steady recovery and all but 2 are at home at the time of writing. CPM may be more prevalent than previously appreciated following liver transplantation, although its prognosis may not be as dismal.

Analysis of initial poor graft function after orthotopic liver transplantation: experience of an australian single liver transplantation center

IN ORTHOTOPIC LIVER transplantation (OLTx), initial poor graft function (IPGF) may be related to the quality of the donor organ, long cold and warm ischemic times, the medical status of the recipient, the surgical technique used, reduced size liver grafts. With IPGF, subsequent patient morbidity and mortality is increased. Primary graft nonfunction (PNF) is the most serious end result of initial poor allograft function and may occur in 1.4% to 8.5% of cases after OLTx and may require urgent re-transplantation to avoid patient mortality. Despite developments in preservation solutions, operative procedures, and new immunosuppressive agents, IPGF continues to be a major complication immediately after OLTx. The definition and criteria used to diagnose IPGF following OLTx is inconsistent in the literature. Evaluation of early graft dysfunction determined by a high level of transaminases [aspartate aminotransferase (AST) or alanine aminotransferase (ALT)] and coagulation activity are often used as appropriate criteria within 7 days after OLTx.) The present study was undertaken as a retrospective analysis of donor and recipient demographics and intraand postoperative biochemical and pathological features to determine the factors leading to IPGF at a single transplant center in Sydney, Australia.

Long-term lamivudine monotherapy prevents development of hepatitis B virus infection in hepatitis b surface-antigen negative liver transplant recipients from hepatitis B core-antibody-positive donors

Abstract:  Background:  Liver transplantation from hepatitis B core‐antibody (HBcAb)‐positive donors to hepatitis B surface‐antigen (HBsAg)‐negative recipients has been associated with a risk of hepatitis B virus (HBV) infection in the absence of antiviral prophylaxis. The aim of this study is to assess the efficacy of long‐term lamivudine monotherapy to prevent development of HBV infection in HBsAg‐negative recipients of liver allografts from HBcAb‐positive donors.

Early high peak hepatitis C viral load levels independently predict hepatitis C–related liver failure post–liver transplantation

The aim of this study was to examine the importance of the serum hepatitis C viral load within the first year post–liver transplant in determining posttransplant survival. A retrospective analysis of 118 consecutive hepatitis C virus–positive liver transplant recipients who received an allograft from January 1997 to September 2005 was undertaken with a median duration of follow‐up of 32.4 months. Univariate and multivariate analyses were used to examine the effects of recipient, donor, surgical, and viral factors on posttransplant outcomes. A total of 620 viral load estimations were undertaken in the first 12 months following transplantation. Patient and graft survival rates at 1, 3, and 5 years were 87.8%, 79.9%, and 70.1% and 87.0%, 79.2%, and 68.2%, respectively. According to multivariate analysis, a peak viral load ≥ 107 IU/mL (P = 0.004; hazard ratio, 8.68; 95% confidence interval, 2.04–37.02) and exposure to antirejection therapy (P = 0.05; hazard ratio, 2.26; 95% confidence interval, 1.01–5.38) were both independent predictors of diminished patient and graft survival and hepatitis C–related allograft failure. The only other independent predictor of hepatitis C virus–related outcome after transplant was azathioprine use, which was associated with improved outcomes (P = 0.04; hazard ratio, 0.25; 95% confidence interval, 0.07–0.91). A peak viral load in the first year after transplant of >108, 107 to 108, and <107 IU/mL was associated with a mean survival of 11.8, 70.6, and 89.1 months respectively (P ≤ 0.03). The results emphasize the importance of high viral loads in the early posttransplant period as an independent predictor of recipient outcomes. Liver Transpl 15:709–718, 2009.

Factors in older cadaveric organ donors impacting on renal allograft outcome

Transplantation of renal allografts (RA) from older donors has become more common, despite conflicting data on outcome between reports from large series versus individual centres. Factors other than donor age per se may contribute to RA outcome. 
The outcome of RA procured from 114 older donors over 55 yr of age in NSW, between 1990 and 1997, was analysed. Corresponding donor factors, including demographics, medical history, inotrope use, major hypotension and findings at procurement, were also analysed. 
Of the potential RA, 8% were discarded and the remainder transplanted. Factors significantly associated with renal discard were pre‐transplantation donation biopsy abnormality (p<0.001) and a history of cardiovascular (CV) disease in the donor (p<0.02). Donor aortorenal atherosclerosis (AS; p<0.09) and a donor age of 65 yr or older (p<0.08) were common in the discard group. The never function rate was 7.6% and was associated with a history of a discarded partner kidney (p<0.05). The delayed graft function rate was 33% and was associated with a history of donor CV disease. At a median follow up of 5 yr, the death censored allograft failure rate was 24%. Allograft failure was associated with a history of donor hypertension (p<0.05). Donor AS (p<0.7) tended to have been more common in the allograft failure group. 
A number of cadaveric organ donor factors documented at procurement may be associated with inferior outcome of RA. These include biopsy abnormality, history of donor CV disease and history of donor hypertension. A donor age of 65 yr or older or significant visible aortorenal AS may also be factors. 
This retrospective review of kidneys procured from 114 older cadaveric organ donors identifies factors apart from donor age, which may have a negative impact on both allograft utilisation and outcome. Theses factors include renal biopsy abnormality, history of donor CV disease, discard of a partner kidney and donor hypertension. Visible AS in the donor aorta documented at renal procurement may also be a factor.

Immunolocalization of FGF-1 and receptors in glomerular lesions associated with chronic human renal allograft rejection.

Glomerular lesions are considered one of the more detrimental pathologic changes associated with chronic rejection of renal allografts. To elucidate potential pathophysiologic mechanisms associated with transplant glomerulopathy, we examined the expression of acidic fibroblast growth factor (FGF-1) and its high-affinity receptors (FGFR) in both relevant renal transplant controls (n=5) and tissue from patients (n=19) who underwent nephrectomy following graft loss secondary to chronic rejection. In situ immunohistochemical analyses demonstrated minimal staining and distribution of FGFR and FGF-1, which was localized to the mesangial matrix in glomeruli from normal human kidneys. In situ hybridization failed to detect the presence of FGF-1 mRNA in control tissue. In contrast, each stage of the developing glomerular lesion associated with chronic rejection demonstrated the exaggerated appearance of FGF-1 protein in visceral and parietal epithelial cells. Intense staining for FGF-1 protein did not correlate with the increased appearance of FGF-1 mRNA, which was restricted to circulating inflammatory cells. Glomeruli in kidneys with findings of chronic rejection also exhibited increased immunodetection of both FGFR and PCNA in mesangial and epithelial cells. Immunogold labeling of chronically rejected visceral epithelial cells revealed both cytoplasmic and nuclear/localization of FGF-1, thereby establishing mitogenic potential of the growth factor. The enhanced appearance of both biologically active FGF-1 and FGFR suggests that this polypeptide may serve as an important mediator of growth responses associated with glomerular lesion development during chronic rejection.