A 10-year experience of liver transplantation for hepatitis C: analysis of factors determining outcome in over 500 patients

OBJECTIVE: To determine the factors affecting the outcome of orthotopic liver transplantation (OLT) for end-stage liver disease caused by hepatitis C virus (HCV) and to identify models that predict patient and graft survival. SUMMARY BACKGROUND DATA: The national epidemic of HCV infection has become the leading cause of hepatic failure that requires OLT. Rapidly increasing demands for OLT and depleted donor organ pools mandate appropriate selection of patients and donors. Such selection should be guided by a better understanding of the factors that influence the outcome of OLT. METHODS: The authors conducted a retrospective review of 510 patients who underwent OLT for HCV during the past decade. Seven donor, 10 recipient, and 2 operative variables that may affect outcome were dichotomized at the median for univariate screening. Factors that achieved a probability value less than 0.2 or that were thought to be relevant were entered into a stepdown Cox proportional hazard regression model. RESULTS: Overall patient and graft survival rates at 1, 5, and 10 years were 84%, 68%, and 60% and 73%, 56%, and 49%, respectively. Overall median time to HCV recurrence was 34 months after transplantation. Neither HCV recurrence nor HCV-positive donor status significantly decreased patient and graft survival rates by Kaplan-Meier analysis. However, use of HCV-positive donors reduced the median time of recurrence to 22.9 months compared with 35.7 months after transplantation of HCV-negative livers. Stratification of patients into five subgroups, based on time of recurrence, revealed that early HCV recurrence was associated with significantly increased rates of patient death and graft loss. Donor, recipient, and operative variables that may affect OLT outcome were analyzed. On univariate analysis, recipient age, serum creatinine, donor length of hospital stay, donor female gender, United Network for Organ Sharing (UNOS) status of recipient, and presence of hepatocellular cancer affected the outcome of OLT. Elevation of pretransplant HCV RNA was associated with an increased risk of graft loss. Of 15 variables considered by multivariate Cox regression analysis, recipient age, UNOS status, donor gender, and log creatinine were simultaneous significant predictors for patient survival. Simultaneously significant factors for graft failure included log creatinine, log alanine transaminase, log aspartate transaminase, UNOS status, donor gender, and warm ischemia time. These variables were therefore entered into prognostic models for patient and graft survival. CONCLUSION: The earlier the recurrence of HCV, the greater the impact on patient and graft survival. The use of HCV-positive donors may accelerate HCV recurrence, and they should be used judiciously. Patient survival at the time of transplantation is predicted by donor gender, UNOS status, serum creatinine, and recipient age. Graft survival is affected by donor gender, warm ischemia time, and pretransplant patient condition. The authors' current survival prognostic models require further multicenter validation.     

Donor Factors Predicting Recipient Survival After Liver Retransplantation: The Retransplant Donor Risk Index

The use of extended criteria liver donors (ECD) is controversial, especially in the setting of retransplantation. The aims of this study are to investigate the effects of ECD grafts on retransplantation and to develop a predictive mortality index in liver retransplantation based on the previously established donor risk index. The United Network for Organ Sharing (UNOS) liver transplant dataset was analyzed for all adult, non-status 1, liver retransplantations occurring in the United States since February 2002. All donors were categorized for multiple characteristics of ECD, and using multivariate survival models a retransplant donor risk index (ReTxDRI) was developed. A total of 1327 retransplants were analyzed. There were 611 (46%) recipients who received livers with at least one ECD criterion. The use of ECD grafts in recipients with HCV did not incur worse survival than the non-ECD grafts. The addition of the cause of recipient graft failure to the donor risk index formed the ReTxDRI. After adjusting for multiple recipient factors, the ReTxDRI was predictive of overall recipient survival and was a strongly independent predictor of death after retransplantation (HR 2.49, 95% CI 1.89–3.27, p < 0.0001). The use of the ReTxDRI can improve recipient and donor matching and help to optimize posttransplant survival in liver retransplantation.     

Extended donor criteria have no negative impact on early outcome after liver transplantation: a single-center multivariate analysis

The organ shortage has driven many transplant centers to accept extended donor criteria and to modify graft allocation policies. This study was designed to analyze the impact of applying extended donor criteria (EDC) in orthotopic liver transplantation (OLT). Between December 2001 and December 2004, we performed 165 primary cadaveric whole OLTs. Up to three EDC, that is, ventilation >7 days; aminotransferases (ALT or AST) >3 x normal; bilirubin >3 mg/dL; anti-HBc or HBs Ag positivity; donor age >65 years; liver steatosis >40%; donor body mass index >30; cold ischemia time >14 hours; peak serum Na(+) >165 mmol/L; history of extrahepatic malignancy; or previous drug abuse were present in 55% of all grafts. Both univariate and multivariate analysis revealed that EDC status had no effect on graft or patient survival, the necessity for retransplantation, the length of intensive care/intermediate care unit stay, mechanical ventilation, complications, or posttransplant laboratory findings. Recipient age of >/=55 years was the only independent prognostic factor for survival, regardless of EDC. These findings suggested that the use of grafts from EDC donors are safe and expand the donor pool.     

Impact of different cadaveric donor age cut-offs on adult recipient survival after liver transplantation: a single-center analysis

The increase in the number of patients awaiting liver transplantation (OLT) has forced the use of cadaveric donors (CD) with suboptimal characteristics. Of these, donor age is perhaps the most investigated parameter. Although excellent outcomes were observed for OLT using CD aged over 60 years, the European Liver Transplant Registry (ELTR) Group found an increased risk by using CD of more than 55 years. The Italian National Transplant Center has recently assumed that CD age more than 60 years is a potential risk factor for OLT. In this study, a single-center analysis was performed by stratifying CD by three age cut-offs (< or =55 or >55, < or =60 or >60, and < or =65 or >65 years) to evaluate effects on OLT outcome. Although no significant difference in 6-month and 1-year patient or graft survival occurred after stratification for each donor age cut-off, a better survival was observed with OLT performed using livers procured from CD >55 years. A significant increase in cold ischemia time (CIT) was observed among OLT performed with grafts procured from CD < or =55 and < or =65 years (P = .007), and there was an inverse correlation between overall CIT and donor age (R = -0.300; P = .0022). However, no impact on 1-year patient survival was observed by introducing CIT in univariate logistic regression models as well as donor age, recipient age, donor/recipient age ratio, donor/recipient sex mismatch, ELTR diagnostic categories, and UNOS status. The results of this study suggest the suitability of CD of more than 55 years for OLT and the need to further investigate the cut-off value for CIT-related risk.     

Analysis of clinical variables of donors and recipients with respect to short-term graft outcome in human liver transplantation

Donor and recipient factors are closely associated with graft survival after orthotopic liver transplantation (OLT). This study was performed to analyze clinical characteristics of recipients and donors, which affect 30-day graft loss after OLT. MATERIALS AND METHODS: One hundred eighty-six livers from heart-beating donors were accepted between May 1997 and June 1998 at the University of Pittsburgh Medical Center. Donor variables that were analyzed included age, sex, cold ischemia time (CIT), warm ischemia time (WIT), imported versus local procurement, cardiopulmonary arrest, serum sodium level, and dopamine dose. The recipient characteristics included native liver disease and UNOS status. Two-sided Fisher exact test and stepwise logistic regression were used for univariate and multivariate analyses. P-values < .05 were considered statistically significant. RESULTS: Twenty-eight grafts (15.1%) were lost within 30 days of OLT. The following factors were found to adversely affect graft survival: donor sodium > 155 mEq/L (P = .002); CIT > 12 hours (P = .002); WIT > 45 minutes (P = .002); and imported liver graft (P = .048). Logistic regression revealed that donor sodium (odds ratio, 3.03; 95% CI, 1.05 to 8.74), CIT (OR 1.20; 95% CI 1.05 to 1.38), WIT (OR 1.06; 95% CI 1.01 to 1.09) were independent predictors of early graft loss. CONCLUSION: Donor hypernatremia as well as warm and cold ischemia times independently affect graft outcomes in the early postoperative period after OLT. Avoidance of long preservation and correction of donor sodium level are recommended to optimize results and survival in OLT.     

Analysis of long-term outcomes of 3200 liver transplantations over two decades: a single-center experience

OBJECTIVE: Few studies have evaluated long-term outcomes after orthotopic liver transplantation (OLT). This work analyzes the experience of nearly 2 decades by the same team in a single center. Outcomes of OLT and factors affecting survival were analyzed. METHODS: Retrospective analysis of 3200 consecutive OLTs that were performed at our institution, between February 1984 and December 31, 2001. RESULTS: Of 2662 recipients, 578 (21.7%) and 659 (24.7%) were pediatric and urgent patients, respectively. Overall 1-, 5-, 10-, and 15-year patient and graft survival estimates were 81%, 72%, 68%, 64% and 73%, 64%, 59%, 55%, respectively. Patient survival significantly improved in the second (1992-2001) versus the era I (1984-1991) of transplantation (P < 0.001). Similarly, graft survival was better in the era II of transplantation (P < 0.02). However, biliary and infectious complications increased in era II. When OLT indications were considered, best recipient survival was obtained in children with biliary atresia (82%, 79%, and 78% at 1, 5, and 10 years, respectively), while malignant disease in adult patients resulted in the worst outcomes of 68% and 43% at 1 and 5 years, post-OLT. Further, patients <18 years and nonurgent recipients exhibited superior survival when compared with recipients >18 years (P < 0.001) or urgent patients (P < 0.001). Of 13 donor and recipient variables, era of OLT, recipient age, urgent status, donor age, donor length of hospital stay, etiology of liver disease, retransplantation, warm and cold ischemia, but not graft type (whole, split, living-donor), significantly impacted patient survival. CONCLUSIONS: Long-term benefits of OLT are greatest in pediatric and nonurgent patients. Multiple factors involving the recipient, etiology of liver disease, donor characteristics, operative variables, and surgical experience influence long-term survival outcomes. By balancing and matching these factors with a given recipient, optimum results can be achieved.     

A single-center experience of late retransplantation of the liver

Liver retransplantation is considered to carry a higher risk than primary transplantation. However, there are an increasing number of retransplant candidates, especially owing to late graft failure. The aim of this study was to analyze a single-center experience in late liver retransplantation. The overall rate of primary retransplantation was 11.4% (28 re-OLT out of 245 primary OLT); the 14 (52%) who underwent retransplantation at more than 3 months after the first transplant were analyzed by a medical record review. Causes of primary graft failure leading to retransplantation were chronic hepatic artery thombosis in five cases (36%); recurrent HCV cirrhosis in four cases (29%); chronic rejection in two cases (14%); veno-occlusive disease; hepatic vein thrombosis or idiopathic graft failure in one case each (7%). UNOS status at re-OLT was always 2A, all patients were hospitalized; three were intensive care unit bound. ICU and total hospital stay had been 7 +/- 5 and 28 +/- 16 days, respectively. One- and 2-year patient and graft survivals were 84% and 62% and 67% and 67%, respectively. Death occurred in four patients. Two out of the three recovered in ICU at the time of retransplantation, at a median interval of 15 +/- 9 days after retransplantation. The survival rate after late retransplantation is improving, and this option should be considered to be a efficient way to save lives, especially by defining the optimal timing for retransplantation.     

The impact of donor variables on the outcome of orthotopic liver transplantation for hepatitis C

Morphologic characteristics of the graft have been proposed as a major contributor to the long-term outcomes in orthotopic liver transplantation (OLT). Our objective was to determine the impact of donor variables, including donor age, donor-recipient HLA match, and type of donation (DCD vs donation after brain death [DBD]), on the outcome of OLT in 192 patients with hepatitis C virus (HCV). Fourteen patients underwent OLT from donation after cardiac death (DCD) donors and 188 from DBD donors. Mean donor age, warm ischemia time at recovery, and cold ischemia time were similar between the groups. Overall graft survival rate at 1 year (55% DCD vs 85% DBD) and 5 years (46% DCD vs 78% DBD) was significantly lower in the DCD group (P = .0003). Similarly, patient survival rate at 1 year (62% DCD vs 93% DBD) and 5 years (62% DCD vs 82% DBD) was significantly lower in the DCD group (P = .0295). Incidences of hepatic artery thrombosis, portal vein thrombosis, and primary nonfunction were similar between the DCD and DBD groups. The incidence of liver abscess with ischemic-type biliary stricture was higher in recipients from DCD as compared with DBD (42% vs 2%). A trend toward lower graft survival was noted in recipients from donors older than 60 years of age in the HCV population (P = .07), with statistically lower patient survival (P = .02). Donor- recipient HLA matching did not appear to correlate with OLT outcome in patients with HCV. DCD donors and donors older than 60 years of age significantly impact patient and graft survival. Lower graft and patient survival in recipients from DCD donors does not appear to be related to early disease recurrence.     

Is the use of marginal donors justified in liver transplantation? Analysis of results and proposal of modern criteria

Abstract  A discrepancy exists worldwide between the number of suitable liver donors and the in creasing demand for transplantation. Thus many centers have considered widening their liver donor acceptance criteria and this may in crease the incidence of primary dysfunction (PD) with negative effect on the results of transplantation. In order to reduce the incidence of PD and improve patient and graft survival it becomes important to identify those risk factors associated with its occurrence. In a retrospective univariate and multivariate analysis we evaluated several donor, preservation and recipient parameters and their correlation with PD. In our Department 282 orthotopic liver transplantations (OLT) were per formed on 256 adult patients over a 10–year period. Excluded were 15 cases with early vascular problems and 4 intraoperative deaths. A complete series of donor, recipient and procedure-related data were ana lyzed. About 30 % of donors showed abnormal values. In 70 cases of PD (26 %) there was a 61.4 % graft failure rate compared with 15 % in the group with immediate function (P < 0.05). Univariate analysis showed donor age, steatosis, is chemia time, amines, oliguria, hy potension and ICU stay to be signif icantly associated with PD. Multi variate analysis showed steatosis, is chemia time and amine dosage to be independent risk factors for the de velopment of primary non function. In conclusion, the acceptance of marginal donors worsened the results of transplantation, but the rejection of these donors would reduce by about 30 % our transplant activity resulting in increased mortality in the waiting list. Combinations of risk factors when possible should be avoided, and ischemia time, as the only variable that can be controlled, should be kept as short as possible.     

Similar liver transplantation survival with selected cardiac death donors and brain death donors

Background:

The outcome of orthotopic liver transplantation (OLT) with controlled graft donation after cardiac death (DCD) is usually inferior to that with graft donation after brain death (DBD). This study compared outcomes from OLT with DBD versus controlled DCD donors with predefined restrictive acceptance criteria.

Methods:

All adult recipients in the Netherlands in 2001–2006 with full‐size OLT from DCD (n = 55) and DBD (n = 471) donors were included. Kaplan–Meier, log rank and Cox regression analyses were used.

Results:

One‐ and 3‐year patient survival rates were similar for DCD (85 and 80 per cent) and DBD (86·3 and 80·8 per cent) transplants (P = 0·763), as were graft survival rates (74 and 68 per cent versus 80·4 and 74·5 per cent; P = 0·212). The 3‐year cumulative percentage of surviving grafts developing non‐anastomotic biliary strictures was 31 per cent after DCD and 9·7 per cent after DBD transplantation (P < 0·001). The retransplantation rate was similar overall (P = 0·081), but that for biliary stricture was higher in the DCD group (P < 0·001). Risk factors for 1‐year graft loss after DBD OLT were transplant centre, recipient warm ischaemia time and donor with severe head trauma. After DCD OLT they were transplant centre, donor warm ischaemia time and cold ischaemia time. DCD graft was a risk factor for non‐anastomotic biliary stricture.

Conclusion:

OLT using controlled DCD grafts and restrictive criteria can result in patient and graft survival rates similar to those of DBD OLT, despite a higher risk of biliary stricture. Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.     

Liver transplantation using donors older than 80 years: a single-center experience

AIM: The shortage of organs for orthotopic liver transplantation (OLT) has forced transplantation centers to expand the donor pool by using donors traditionally labeled as "extended criteria donors." One such example is OLT using a donor with advanced age. MATERIALS AND METHODS: We retrospectively evaluated 10 patients who received a liver graft from cadaveric donors older than 80 years. We analyzed pretransplantation donor and recipient characteristics, as well as the evolution of the recipients. RESULTS: All 10 donors were older than 80 years (median age, 83.5; range, 80-93). No steatosis (>30%) was accepted in the older donor group. Medium follow-up was 19.5 months. The most frequent cause for OLT was hepatitis C virus (HCV) cirrhosis (8/10 patients). We had 1 case of primary nonfunction, 1 patient died immediately after surgery because of extrahepatic complications (cardiac arrest), and 2 other patients had a severe HCV recurrence and died after 1 and 2 years from OLT, respectively. Five patients had HCV recurrence and biliary complications were present in 60% of the patients. No cases of acute or chronic rejection were described. Overall survival rates after 1 and 3 years were 80% and 40%, respectively. CONCLUSIONS: Old donor age is not an absolute contraindication to OLT. Liver grafts from donors older than 80 years can be used knowing that there is a high risk of postoperative complications. Furthermore, the increased risk of developing severe HCV recurrence, related to older donor age, suggests that such livers should be used in HCV-negative recipients.     

Outcomes of adult-to-adult living donor liver transplantation: a single institution's experience with 335 consecutive cases

OBJECTIVE: To determine outcomes for both donors and recipients of adult-to-adult living donor liver transplantation (AALDLT) and independent factors impacting those outcomes. SUMMARY BACKGROUND DATA: Deceased donors for organ transplantation remain extremely rare, making living donor liver transplantation (LDLT) practically the sole therapeutic modality for patients with end-stage liver disease in Japan. METHODS: Retrospective analysis of initial LDLT for 335 consecutive adult (>or=18 years) patients performed between November 1994 and December 2003. RESULTS:: Of the 335 recipients, 275 received right-liver grafts and the remaining 60 recipients received non-right-liver grafts. Three of the 335 liver grafts were domino-splitting livers. Sixty of the 332 donors other than the domino-donors showed major postoperative complications. Multivariate analysis indicated that accumulation of case experience significantly and advantageously affected the surgical outcomes of these living liver donors, and right-liver donation and prolonged donor operation time were shown to be independent risk factors of major complications in the donors. Post-transplant patient and graft survival estimates were 73.1% and 72.5% at 1 year, 67.7% and 66.3% at 4 years, and 64.7% and 61.9% at 7 years, respectively. Obvious pretransplant encephalopathy, a higher (>or=31) modified Model for End-stage Liver Disease score (including points for persistent ascites and low serum sodium) and higher donor age (>or=50 years) were indicated as independent factors predictive of graft failure (graft loss or death) in the multivariate analysis. CONCLUSIONS: Graft type and degree of experience exerted a significant impact on the surgical outcomes of AALDLT donors but did not significantly affect the survival outcomes of AALDLT recipients. Better pretransplant conditions and younger age (<50 years) among the living donors appeared to be advantageous in terms of gaining better survival outcomes of patients undergoing AALDLT.     

MELD and prediction of post-liver transplantation survival.

The model for end-stage liver disease (MELD) was developed to predict short-term mortality in patients with cirrhosis. It has since become the standard tool to prioritize patients for liver transplantation. We assessed the value of pretransplant MELD in the prediction of posttransplant survival. We identified adult patients who underwent liver transplantation at our institution during 1991-2002. Among 2,009 recipients, 1,472 met the inclusion criteria. Based on pretransplant MELD scores, recipients were stratified as low risk (< or = 15), medium risk (16-25), and high risk (>25). The primary endpoints were patient and graft survival. Mean posttransplant follow-up was 5.5 years. One-, 5- and 10-year patient survival was 83%, 72%, and 58%, respectively, and graft survival was 76%, 65%, and 53%, respectively. In univariable analysis, patient and donor age, patient sex, MELD score, disease etiology, and retransplantation were associated with posttransplantation patient and graft survival. In multivariable analysis adjusted for year of transplantation, patient age >65 years, donor age >50 years, male sex, and retransplantation and pretransplant MELD scores >25 were associated with poor patient and graft survival. The impact of MELD score >25 was maximal during the first year posttransplant. In conclusion, older patient and donor age, male sex of recipient, retransplantation, and high pretransplant MELD score are associated with poor posttransplant outcome. Pretransplant MELD scores correlate inversely with posttransplant survival. However, better prognostic models are needed that would provide an overall assessment of transplant benefit relative to the severity of hepatic dysfunction.     

Donors older than 70 years in liver transplantation

INTRODUCTION: Expansion of donor criteria has become necessary with the increasing number of liver transplantation candidates, as aged donors who have been considered to yield marginal organs. METHODS: Our database of 477 liver transplants (OLT) included 55 cases performed from donors at least 70 years old vs 422 with younger donors. We analyzed pretransplantation donor and recipient characteristics as well as evolution of the recipients. RESULTS: The old donor group showed significantly lower ALT (23 +/- 17 vs 48.9 +/- 67; P = .0001) and LDH (444 +/- 285 vs 570 +/- 329; P = .01). There was a trend toward fewer hypotensive events in the aged donor group (27.2% vs 40.5%; P = .07). No steatosis (>10%) was accepted in the old donor group. Cold ischemia time was statistically shorter for the aged donors (297 +/- 90 minutes vs 346 +/- 139 minutes; P = .03). With these selected donors, the results were not different for primary nonfunction, arterial and biliary complications, hospitalization, acute reoperation or acute retransplantation, and hospital mortality when donors > or =70 years old were compared to younger donors. Functional cholestasis, neither related to rejection nor to biliary complications, was seen more frequently in old donor recipients (40% vs 22%; P = .03). No differences in 1, and 3 year survivals were observed between recipients of donors over 70 years old and these of younger organs: 93.8% and 90.6% vs 90.7% and 82.8%, respectively. CONCLUSION: When using selected donors > or =70 years old the outcomes were comparable to those obtained with younger donors. Strict selection is necessary to achieve good long-term survival.     

Effect of nonviral factors on hepatitis C recurrence after liver transplantation

OBJECTIVE: Hepatitis C (HCV) is now the most common indication for orthotopic liver transplantation (OLT). While graft reinfection remains universal, progression to graft cirrhosis is highly variable. This study examined donor, recipient, and operative variables to identify factors that affect recurrence of HCV post-OLT to facilitate graft-recipient matching. METHODS: Retrospective review of 307 patients who underwent OLT for HCV over a 10-year period at our center. Recurrence of HCV was identified by the presence of biochemical graft dysfunction and concurrent liver biopsy showing diagnostic pathologic features. Time to recurrence was the endpoint for statistical analysis. Five donor, 6 recipient, and 2 operative variables that may affect recurrence were analyzed by univariate comparison and Cox proportional hazard regression models. RESULTS: Recurrence-free survival in the 307 study patients was 69% and 34% at 1 and 5 years, respectively. Four predictive variables related to either donor or recipient characteristics were identified. Advanced donor age, prolonged donor hospitalization, increasing recipient age, and elevated recipient MELD scores were found to increase the relative risk of HCV recurrence. Examination of HLA disparity between donors and recipients demonstrated no correlation between class I or class II mismatches and recurrence-free survival. CONCLUSIONS: We have identified donor and recipient characteristics that significantly predict hepatitis C recurrence following liver transplantation. These factors are identifiable before transplant and, if considered when matching donors to HCV recipients, may decrease the incidence of HCV recurrence after OLT. A change in the current national liver allocation system would be needed to realize the full value of this benefit.     

Liver retransplantation: a model for determining long-term survival

BACKGROUND: Because of the worse results from retransplantation in relation to the initial liver transplantation, there is a need to refine the indication for retransplantation, such that fair distribution of this benefit is obtained. METHODS: This was a study of 139 patients who underwent liver retransplantation. Thirty variables were studied: 18 relating to the recipient and 12 to the donor. All the independent variables were initially compared with the length of survival using univariate analyses. Variables presenting significance were compared with the dependent variable of length of survival, to determine which factors were related to longer survival among patients, when evaluated together. RESULTS: A multivariate model for determining long-term survival among patients with retransplants was built up using the following variables: recipient's age, creatinine, urgency of retransplantation and early failure of the first graft. Through this multivariate model it was possible to determine a score that was categorized according to tertile distributions (below the 33rd percentile, score <24; 33rd to 66th percentile, 24 < or = score < or = 32; above the 66th percentile, score > 32). One-year, 3-year, and 5-year patient survival rates following retransplantation were respectively 85%, 82%, and 77% for scores <24; 69%, 66%, and 61% for scores between 24 and 32; and 21%, 19%, and 16% for scores >32 (P < 0.0001). CONCLUSION: The variables of recipient's age, creatinine, urgency of retransplantation, and early failure of the initial transplantation were factors that were independently related to the long-term survival of patients with liver retransplants.     

Histological recurrent hepatitis C after liver transplantation: Outcome and role of retransplantation.

Impact of hepatitis C virus (HCV) recurrence on long-term outcome after orthotopic liver transplantation (OLT) is highly variable, and the role of retransplantation is still debated. From 1996 to 2003, 131 OLT with histologically proven HCV recurrence and 6 months of follow-up were retrospectively reviewed. One and 5-yr overall survivals were 90.7 and 81.3%, respectively. The mean time of HCV recurrence was 10.1 +/- 6.2 months in patients whose donor's age was less than 70 yr old, and 6.6 +/- 4.7 in patients whose donor's age was more than 70 (P < 0.01). The mean time between OLT and HCV recurrence was 10.7 +/- 8.2 months among patients still alive, and 5 +/- 4.2 among the 20 who died (P = 0.02). In 16 (12.2%) patients, retransplantation was required for severe HCV recurrence; 5 are still alive and 11 (68.7%) died. The mean survival time was 16.2 +/- 6 months if re-OLT was performed within 12 months from first OLT, and it was 45.9 +/- 10 months if re-OLT was performed later (P < 0.01). In conclusion, donors older than 70 yr are at high risk of early HCV recurrence; expectancy of life is significantly reduced in case of histologically proven recurrence within 6 months. Outcome is quite dismal in patients with early HCV recurrence requiring retransplantation within 1 yr of first OLT.     

Some remarks on the management of liver donor

We evaluated 481 liver donors in order to assess the incidence of positive cultures on samples obtained before harvesting, at harvesting and on preservation fluid; to determine factors related to positive cultures in the donor; to analyse the bacterial and fungal transmission from donor to recipient; to verify the influence of donor culture positivity on graft and patient survival. Cultures were positive in 232 of 481 (48%) donors. Bacteremia was present in 101 of 481 (20%) donors. Intensive care length of stay was significantly longer in culture-positive donors. A Gram-negative bacteria transmission from the infected donor to the graft recipient was proven in 1 case. No differences in 1-year survival and retransplantation rates were found between patients receiving livers from culture-positive or negative donors. In conclusion, even if rare, donor to host infection transmission is proven. Extended criteria for organ procurement may explain the high number of culture-positive donors we report. Careful microbiological surveillance and treatment can reduce the clinical negative impact on recipient outcome.     

Marginal grafts: finding the correct treatment for fatty livers

The influence of steatosis on the outcome of orthotopic liver transplantation (OLT) was evaluated in 860 liver transplantations carried out in 784 patients from October 1990 to August 2001. Donor variables considered were: age, hepatic enzymes, bilirubin, total and warm ischemia times, macrovesicular and microvesicular steatosis. Recipient variables considered were: age, UNOS status, Child-Pugh score and indication for OLT. Patient and graft survival were the main outcome indicators. Macrovesicular steatosis affecting 15% or more of the hepatocytes was the only variable independently associated with shorter patient and graft survival ( P=0.0012 and 0.0028). A significantly worse prognosis was to be expected if >15% macrovesicular steatosis was associated with a total ischemia time >10 h ( P=0.048), or donor age >65 years ( P=0.016) or with HCV-positive recipients ( P=0.0014). From our study we can conclude that macrovesicular steatosis involving 15% or more of the hepatocytes identifies marginal livers. The risk of graft non-function or patient loss after OLT rises if macrovesicular steatosis >15% is associated with long ischemia time, high donor age, or HCV positivity in recipients.     

Older donor livers show early severe histological activity, fibrosis, and graft failure after liver transplantation for hepatitis C

BACKGROUND: In hepatitis C virus (HCV)-positive liver transplant recipients, infection of the allograft and recurrent liver disease are important problems. Increased donor age has emerged as an important variable affecting patient and graft survival; however, specific age cutoffs and risk ratios for poor histologic outcomes and graft survival are not clear. METHODS: A longitudinal database of all HCV-positive patients transplanted at our center during an 11-year period was used to identify 111 patients who received 124 liver transplants. Graft survival and histological endpoints (severe activity and fibrosis) of HCV infection in the allografts were compared as a function of donor age at transplantation. RESULTS: By Kaplan-Meier analyses, older allografts showed earlier failure and decreased time to severe histological activity and fibrosis as compared with allografts from younger donors. By Cox proportional hazards analysis, older allografts were at greater risk for all severe histologic features and decreased graft survival as compared with younger allografts (P< or =0.02 for all outcomes). Analysis of donor age as a dichotomous variable showed that donors greater than 60 yr were at high risk for deleterious histologic outcomes and graft failure. An age cutoff of 60 yr showed a sensitivity of 94% and specificity of 67% for worse graft survival by receiver operating characteristics curve. CONCLUSIONS: Advanced donor age is associated with more aggressive recurrent HCV and early allograft failure in HCV-positive liver transplant recipients. Consideration of donor age is important for decisions regarding patient selection, antiviral therapy, and organ allocation.