M. F. Levy

Hla Compatibility And Liver Transplant Outcome Improved Patient Survival by Hla and Cross-matching

In liver transplantation (LTx), numerous studies have failed to demonstrate an adverse effect of HLA-A,B,DR incompatibility or of donor-specific positive cross-match on survival of the recipients. In this study, we examined the effect of antidonor cytotoxic antibody and HLA compatibility in 800 LTx recipients with CsA-based immunosuppression. Thirty-four of 482 (7%) recipients were transplanted across a positive donor-specific T cell cross-match. Four-year patient and graft survival was 71% and 67%, respectively, in negative cross-match recipients and 53% and 50%, respectively, in positive cross-match recipients (P=0.0051 and P=0.023). Neither B cell-positive cross-match nor the presence of panel reactive antibody (PRA) had an adverse impact on the liver allograft outcome. Interestingly, 21/58 (36.2%) patients with PRA ≤ 10% had a positive T cell cross-match, whereas only 7/382 (1.8%) patients with PRA < 10% did (P<0.0001). This indicates the predictive value of PRA cross-match results. B lymphocyte cross-match results also were strongly correlated with the presence of PRA, as 26/57 (45.6%) of the patients with PRA ≥ 10% had a positive cross-match, whereas only 22/394 (5.6%) with PRA < 10% did (P<0.0001). Analysis of HLA compatibility demonstrated a significant impact on patients survival, comparing only 0–2 vs. 6 HLA-A+B+DR mismatches and 0 vs. 1 vs. 2 HLA-DR mismatches. Four-year patient survival rate for 0 to 2 antigen mismatches was 86%, whereas for 6 antigen mismatches it was 62% (P=0.025). Overall actuarial 4-year patient survival rate in HLA-DR-mismatched groups (0 vs. 1 vs. 2) was 84%, 73%, and 64%, respectively (P=0.033). In no mismatched category was graft survival rate significantly different. Sepsis or rejection was the cause of graft loss in 1/10 (10%), 21/75 (28%), and 34/85 (40%) patients with 0, 1, and 2 HLA-DR mismatches, respectively. The difference between patient and graft survival was accounted for by survival after retransplantation, which was lower in patients with more HLA-DR mismatches in primary transplants. The latter group received intensive immunosuppressive therapy during the first month after primary transplantation, as compared with those with fewer HLA-DR mismatches (P=0.04).

FK506 trough levels in whole blood and plasma in liver transplant recipients. Correlation with clinical events and side effects.

FK506 trough levels were measured by ELISA in paired whole-blood and plasma samples in 59 liver transplant recipients. Patients with nephrotoxicity had higher FK506 whole-blood and plasma levels (27.5 +/- 3.2 ng/ml and 1.44 +/- 0.14 ng/ml) than patients with stable liver function (15.2 +/- 2.1 ng/ml and 0.98 +/- 0.15 ng/ml, P < 0.05 and P < 0.01, respectively). Patients with acute rejection had FK506 whole-blood and plasma levels within the same range as patients with stable liver function. Patients with severe neurotoxicity had significantly higher FK506 whole-blood and plasma levels (31.3 +/- 6.8 ng/ml and 3.9 +/- 1.4 ng/ml) in comparison with patients with mild-to-moderate neurotoxicity (18.1 +/- 2.4 ng/ml and 1.1 +/- 0.13 ng/ml) (P = 0.048 and P < 0.001, respectively). Long-term use of FK506 was associated with a significant reduction in glomerular filtration rate at 1-year posttransplant in patients on primary FK506 treatment (33%, P < 0.001). The reduction in glomerular filtration rate correlated with the yearly mean FK506 plasma but not with whole-blood levels or FK506 dose. There was a correlation between FK506 whole-blood and plasma levels (r = 0.713, P < 0.001) but not between the levels (whole blood or plasma) and FK506 dose (mg/day or mg/kg/day). The mean FK506 whole-blood and plasma levels were 14.1 +/- 0.26 ng/ml and 0.96 +/- 0.75 ng/ml, respectively. There was a large intra- and interpatient variability in the ratio between whole-blood and plasma levels (range 1.0-73.5), with a mean ratio of 18.0 +/- 0.28 (+/- SEM). In conclusion, monitoring of FK506 trough levels is of importance to avoid nephro- and neurotoxicity, but monitoring is only of limited help to avoid acute rejection. Monitoring of FK506 levels in plasma seems to be superior to that in whole blood.

Liver and kidney transplantation for polycystic disease.

BACKGROUND With the poor results of resective and fenestration procedures for polycystic liver disease (PCLD), we present the first series of patients receiving orthotopic liver transplantation for this condition. METHODS Five of our six patients with PCLD had polycystic kidney disease also. Three of these five received combined organ transplants, while the other two required subsequent kidney transplants. RESULTS Forty-eight and 52 months after orthotopic liver transplantation, all surviving patients had relief of their pain, distention, and anorexia. Two patients had succumbed to infectious complications and died at 15 and 24 months after transplant. CONCLUSIONS We conclude that patients with PCLD can be transplanted safely for the relief of their distention and anorexia, with good results. Those patients with both PCLD and polycystic kidney disease who are not dialysis dependent can be managed for several years with isolated liver transplantation and then receive kidney transplantation if needed. Those who are dialysis dependent should receive combined liver-kidney transplantation. Unfortunately, patients with polycystic disease seem to be very susceptible to infectious complications after organ transplantation.

Effect of pentoxifylline on hepatic ischemia and reperfusion injury

BACKGROUND Although pentoxifylline has been shown to improve tissue oxygenation and restore hepatocellular function after hemorrhagic shock, its effect on hepatic ischemia and reperfusion injury has not been fully clarified. The purpose of this study was to determine whether pentoxifylline exerted beneficial effects on liver histopathologic changes and enzymatic release caused by ischemia and reperfusion. METHODS Warm, reversible hepatic ischemia/reperfusion injury was induced in four groups of pigs. Preoperative oral (24 mg/kg or 50 mg/kg) or intraoperative intravenous (50 mg/kg) pentoxifylline was administered. Control animals received intravenous normal saline solution. RESULTS Untreated control animals exhibited significant liver damage expressed by hepatic histopathologic changes and high plasma levels of aminotransferases. Decreased animal survival was seen in the untreated group. All treated animals survived. Pentoxifylline given orally did not improve histopathologic changes or enzyme release. Intravenous administration caused significant amelioration of liver tissue damage, marked reduction of aspartate aminotransferase levels, and mild attenuation of alanine aminotransferase levels, as compared with control. CONCLUSIONS This study indicates that intraoperative, intravenous pentoxifylline reduces hepatic injury after warm ischemia and reperfusion.

Comparing quality of life following liver transplantation for Laennec's versus non-Laennec's patients.

The overall success of orthotopic liver transplantation (OLTX) includes not only survival, but quality of life (QOL) as well. We studied one controversial group of OLTX recipients, patients transplanted for alcoholic liver disease (Laennecs), to determine if their post‐OLTX QOL was similar to that of patients transplanted for non‐alcoholic liver disease (non‐Laennecs). Over a 10‐yr period, patients undergoing OLTX at our institution were asked to complete a QOL questionnaire addressing a wide range of topics from demographics and employment to symptom distress/frequency, activities of daily living, and effect of loss of health on daily life. Twenty‐four Laennecs and 100 non‐Laennecs OLTX recipients completed the questionnaire at both their 2‐ and 5‐yr follow‐up visits at our institution. Both groups were well‐matched in age, race, and patient location status at the time of OLTX. No significant differences could be detected between Laennecs and non‐Laennecs scores regarding overall QOL, including ones ability to function, health perception, and self‐perception at 2 and 5 years post‐OLTX, and between 2 and 5 years post‐OLTX. Although not between groups, a significant difference was noted regarding patients’ satisfaction with life, with less satisfaction reported at the 5‐yr versus the 2‐yr time point post‐OLTX. Rates of current/recent employment between both groups were also similar at 2 years post‐OLTX, and again at 5 years post‐OLTX. We conclude that overall QOL and employment levels appear similar between patients transplanted for alcoholic and non‐alcoholic liver disease. This similarity appears to extend to 5 years post‐OLTX.

Guidelines for surgical procedures after liver transplantation.

OBJECTIVE The first purpose of this study is to identify the types and incidences of surgical procedures in patients who have previously undergone liver transplantation, with particular focus on the complication rates and the lengths of hospital stay. The second purpose is to present the management guidelines for patients with liver transplants at the preoperative, intraoperative, and postoperative stages of surgical procedure. SUMMARY BACKGROUND DATA The surgical literature on this issue is scant, and with the growing liver transplant patient population it is not unlikey for any surgery specialist to have to operate on a patient who has undergone liver transplantation. METHODS A sample of 409 patients with available hospital records, with a minimum of a 2-year follow-up, and with telephone access for interviews was chosen. Type of surgery, time from the liver transplant, hospital stay, immunosuppressive regimen, and complications were recorded. RESULTS A large proportion of patients (24.2%) underwent some type of surgical procedure 2 to 10 years after liver transplantation. The authors demonstrate that most of the elective procedures can be safely carried out without an increased incidence of complication and without longer hospital stay than the general population. Conversely, emergent procedures are plagued by a greater incidence of complications that not only affect the function of the liver graft but may risk the life of the patient.

Radio-frequency ablation of hepatocellular carcinoma before liver transplantation: a histologic and ‘TUNEL’ study

Abstract: Background: Radio‐frequency ablation (RFA) is an increasingly used treatment modality for hepatocellular carcinoma (HCC) in patients awaiting liver transplantation (OLTX). The current study evaluates the effectiveness of RFA in this setting based on evaluation of total cell death in explanted native livers.

Influence of donor and recipient gender on the outcome of liver transplantation

BACKGROUND Gender is currently not a criterion in the allocation of scarce donor organs. The purpose of this study was to determine the effects of gender on patient and graft survival, incidence of rejection, and postoperative complications after orthotopic liver transplantation. METHODS During a 10-year period, 1138 liver transplants were performed on 1010 adult patients at Baylor University Medical Center. In this study, 994 patients with at least 6 months of posttransplant follow-up were reviewed. The four combinations of gender match and mismatch included: group 1, donor female to recipient female (n=229); group 2, donor female to recipient male (n= 126); group 3, donor male to recipient female (n=247); and group 4, donor male to recipient male (n=392). These groups were evaluated for patient survival, graft survival, episodes of rejection, incidence of chronic rejection, and postoperative complications. RESULTS All groups were similar with respect to recipient age, underlying medical condition, incidence of bacterial and viral infections, postoperative biliary complications, and the incidence of chronic rejection. Female recipients had the highest incidence of early rejection (0-6 months, 70%) compared with male recipients (60%, P<0.039). Postoperative vascular complication (10%) was highest in group 3 (P<0.01). The two-year graft survival rate for groups 1, 3, and 4 was 76.2%, 75.6%, and 73.5%, respectively. Group 2, donor female to recipient male, had a 2-year graft survival rate of 55.9% (P<0.0001). This finding is not explained by the incidence of early rejection. Chronic rejection does not appear to be contributory. The mean donor age for groups 1, 3, and 4 was 35.7, 25.8, and 30.4 years, respectively. The mean donor age for group 2 was slightly older, at 41.6 years (P<0.0001). This difference, while statistically significant, is of unknown clinical relevance. A multivariate analysis controlling for donor age confirmed the decreased graft and patient survival rates in the donor female to recipient male group. CONCLUSIONS The decreased graft survival rate in male recipients of female livers warrants further study and may argue for modifying the current management of adult male liver transplant recipients.

Lower Incidence of Acute Cellular Rejection in Liver Transplant Recipients More than 60 Years of Age Allows Minimization of Immunosuppression: 2300

With increased survival rates after liver transplantation (LTX), current posttransplant treatment aims at minimizing long term complications and side effects of immunosuppression. We analyzed whether donor or recipient age have impact in the incidence of acute cellular rejection (ACR) in the first 6 months after LTX. 1275 patients underwent primary LTX at one institution btween 20012010. Data collected prospectively was analyzed retrospectively. 230 patients (18%) were over the age 60 (P60), and 1145 were younger (82%). Patients aged > 60 received lighter immunosuppression by protocol. Their disease severity by MELD score was lower than of younger patients (median laboratory MELD 15 in patients >60 and 17 in younger patients, p=0.0002) Patients with ACR had a lower median age (51 vs. 53with no ACR, p=0.0006). Patients aged >60 had an ACR incidence of 26.4% when receiving organs from donors > 50 years old, 28.8% with organs from donors < 50. Their younger counterparts (< 60) had ACR rates of 39.2% with organs from donors >50 and 34.7% with younger donors (p=0.0381). Steroid resistant rejection was found in 3.5% of patients aged >60 and 5.9% in younger patients (p=0.0381). In contrast, patients transplanted with organs from donors >50 had more steroid-resistant ACR (p=0.026). Univariate logistic regression showed age>60 as the only factor associated with less ACR (OR 0.68, p=0.0159). Univariate regression in patients aged > 60 did not reveal risk factors of significance for ACR. Donor age >50 was associated with an increased risk for steroid resistant ACR (OR 1.78, p=0.0184) in stepwise logistic regression analysis, but not with steroid sensitive ACR. In conclusion, despite the use of less heavy immunosuppression and a lower pretransplant disease severity, patients aged > 60 have a lower incidence of ACR. This justifies minimization of immunosuppression in this patient age category to allow reduction of side effects and less complications from immunosuppressant medication. 1563

THE POSITIVE CROSSMATCH IN LIVER TRANSPLANTATION: A RISK FACTOR FOR PRESERVATION INJURY?: 398

R. Ruiz1, K. Tomiyama2, S. Chinnakotla2, R. Goldstein3, M.F. Levy4, G.J. McKenna3, N. Onaca4, H. Randall5, B. Susskind2, L. Jennings5, G.W. Tillery2, G. Klintmalm6 1Transplant Surgery, Baylor University Medical Center, Dallas/ Texas/UNITED STATES OF AMERICA, 2Transplant Surgery, Baylor University Medical Center, Dallas/UNITED STATES OF AMERICA, 3Transplant Services, Baylor Regional Transplant Institute, Dallas/ TX/UNITED STATES OF AMERICA, 4Islet Cell Transplant Program, Baylor Regional Transplant Institute, Dallas/UNITED STATES OF AMERICA, 5Transplant, Baylor University Medical Center, Dallas/TX/ UNITED STATES OF AMERICA, 6, Baylor University Medical Center, Dallas/UNITED STATES OF AMERICA