Redistribution of renal allograft-responding leukocytes during rejection. II. Kinetics and specificity.

We investigated the traffic of allograft-responding leukocytes between the host and graft without handling of these cells in vitro. The blood flow between the host and graft was disconnected, the proliferating cells were labeled with [3H]thymidine selectively in the graft or in the host, the label was chased with cold thymidine, and the circulation was reestablished. The localization of labeled cells was quantitated by autoradiography. The first host-derived labeled cells appeared in the graft and graft-derived labeled cells in the host, already on the 1st d after transplantation. This was followed by an exponential increase in the labeled cell traffic in both directions. The peak of traffic was observed on day 4 after transplantation, whereafter the traffic rapidly declined and tapered off. This decline was not due to exhaustion of supply, as the labeled cells continued to proliferate in their original compartments, nor to a slowdown of blood circulation, which took place 2-3 d later. We consider the decline to indicate that the rejection has proceeded to a (irreversible) stage autonomous of the host lymphatic and hematopoietic system. During the exponential increase, nearly one-third of the graft-infiltrating inflammatory cells were replaced as a consequence of relocalization during each 18-h-period. All mononuclear white cell types, with the exception of granulocytes, participated in the traffic. Most lymphoid cells entrapped in the graft were descendents of recent cell divisions; most of the mononuclear phagocytes derived from a preexisting phagocyte pool. The entrapment of labeled leukocytes in a relevant graft was specific: when an allograft and an autograft were simultaneously transplanted, a more than 50-fold entrapment was observed in the allograft, compared with the autograft. Very few of the cells localized in irrelevant positions, such as the liver and lung, of the recipient.

Coccidioidomycosis and renal transplantation.

Two cases of coccidioidomycosis detected in a group of more than 750 renal transplants are presented. The first patient died from unsuspected disseminated coccidioidomycosis 4 1/2 years after primary transplantation and 6 days after retransplantation. In the second patient pulmonary coccidioidomycosis was recognized and treated by lobectomy and amphotericin B before transplantation; subsequent transplantation has provided good renal function without recurrence of infection for 5 years. Experience with six other reported cases of coccidioidomycosis illustrates the high risk of exacerbation and dissemination of preexisting coccidioidal infection in immuno-suppressed transplanted recipients. Nevertheless, this risk can be made acceptable if active coccidioidomycosis is treated vigorously before immunosuppression is started and if the possibility of exacerbation of infection after transplantation is carefully monitored.

Postoperative deep venous thrombosis after renal transplantation. Effects of cyclosporine.

In this prospective study the frequency of deep venous thrombosis during the first three weeks after renal transplantation was determined using a combination of strain gauge plethysmography and thermography for objective diagnosis. Ninety-seven consecutive patients were studied, 30 patients having juvenile diabetes mellitus. As immunosuppression cyclosporine and low-dose steroids were used. The series was compared with a similar group of 83 patients, 33 having juvenile diabetes mellitus treated with azathioprine and high-dose steroids as immunosuppression, in which the diagnosis of deep venous thrombosis was made with an identical technique. The overall frequency of thrombosis was 9.3% in the cyclosporine-treated group, which is a significant reduction in comparison with the azathioprine group (24.1%). It is concluded that the combination of cyclosporine and low-dose steroids does not increase the frequency of deep venous thrombosis in comparison with azathioprine and high-dose steroids in renal transplanted patients.

Long-term survival and renal function following liver transplantation in patients with and without hepatorenal syndrome--experience in 300 patients.

We have retrospectively reviewed the first 308 patients undergoing orthotopic liver transplantation (OLTX) at our institution to determine the following: 1) To what extent does renal function deteriorate postoperatively? 2) To what extent does renal function recover after OLTX for hepatorenal syndrome (HRS)? 3) What is the survival rate of patients with HRS compared with those without HRS? In non-HRS patients, GFR declined from 97.1 +/- 2.9 cc/min to 56.6 +/- 2.4 cc/min at 6 weeks postoperative, 62.6 +/- 2.6 cc/min at 1 year, and 58.3 +/- 3.5 cc/min at 2 years. In HRS patients, GFR increased from 19.9 +/- 3.6 cc/min to 32.5 +/- 3.1 cc/min at 6 weeks, 45.9 +/- 5.5 cc/min at 1 year, and 37.9 +/- 5.9 cc/min at 2 years. Dosages of cyclosporine were comparable in both groups. There was no difference in perioperative (90-day) mortality. One- and 2-year actuarial survival rates in the non-HRS patients were 87.2% and 82.1%, respectively. The actuarial 1- and 2-year survival rate for the HRS patients was 76.6% (P = NS). Ten percent of HRS patients developed ESRD posttransplant compared with 0.8% of non-HRS patients (P less than 0.005). We conclude that patients with HRS can safely undergo OLTX with acceptable perioperative mortality and good long-term survival. Most HRS patients have return of acceptable renal function. Patients without HRS have a severe decline in GFR posttransplant, which is stable up to 3 years posttransplant.

Late-onset acute rejection in orthotopic liver transplantation--associated risk factors and outcome.

A retrospective review of 375 consecutive orthotopic liver transplants was performed to determine the incidence and outcome of late rejection episodes ([LR] rejection occurring more than 6 months following transplant). A total of 31 episodes in 26 patients were identified. Eighteen of these episodes were associated with subtherapeutic levels of cyclosporine. Of these, 7 were due to noncompliance, 2 were due to biliary strictures, and 1 was due to malabsorption in a cystic fibrosis patient. All 31 episodes were treated initially with steroids, and 22 had a complete response, although one progressed to chronic rejection over a year later. Of the remaining 9, 1 received FK506 with a complete response, and 8 received OKT3. Of the 8 patients who received OKT3, 5 had a complete response, 1 received RS61443 following OKT3 and progressed to chronic rejection, and the remaining 2 received further steroids. Of these 2, 1 had a complete response following the steroids while the second was converted to FK506 with a complete response. Compared with 315 acute rejection episodes ([AR] occurring less than 6 months posttransplant), patients with late rejection episodes had an equivalent response to steroids (63.2% AR reversed vs. 71% LR reversed) but a lower response rate to OKT3 (91.5% AR reversed vs. 62.5% LR reversed). There was, therefore, a higher rate of persistent rejection (61% AR episodes vs. 15.4% LR episodes) but no increase in the incidence of chronic rejection (7% AR episodes vs. 7.7% LR episodes). We conclude that LR is a relatively common occurrence following liver transplant, which is most often associated with low cyclosporine levels. Many of these episodes are due to noncompliance, but biliary problems must also be investigated. The incidence of resistant rejection is higher in this group of patients but is not associated with a concurrent increase in chronic rejection.

Urine plasmin-like substances as an index of kidney allograft rejections.

Using solid state radioimmunoassays developed by the first author, changes in the urine level of plasmin-like substances (PLS) and fibrin degradation products (FDP) before and after human kidney transplantation were determined in 49 transplant patients. Averages of urine PLS and FDP in a normal population of 51 persons were 0.13+/-0.10 (SD) and 0.14+/-0.07 microng/ml, respectively. In all transplant patients there was an initial rise of both PLS and FDP in urine immediately after transplantation. This elevation peaked on days 4 and 5 and the PLS and FDP levels returned to normal range within 2 weeks in patients without evidence of rejeciton. A secondary rise of urine PLS was detected before or with a rise in serum creatinine in all of the patients experiencing rejections. Of 11 patients who showed a rejection episode within 2 weeks of transplantation, the secondary rise of urine PLS was detectable in 55% of the patients slightly before the serum creatinine level changes; of 6 patients with a rejection episode more than 2 weeks after transplantation, 100% showed a secondary PLS rise 6.7+/-2.3 (SE) days before the serum creatinine increased. The appearance of the secondary rise of urine FDP in the rejecting recipients was slightly later than the rise of PLS. Serial determination of urine PLS levels following human kidney transplantation appears to be an early index of rejections which occurs more than 2 weeks after transplantation, although the clinical usefulness of this measurement is probably limited.

Simultaneous liver and renal transplantation in man.

Advanced chronic renal failure has been thought of as a contraindication to liver transplantation. We present here seven cases of simultaneous kidney-liver transplant performed for combined end-organ failure. Six of the seven patients are alive with functioning grafts with follow-up of from 6 weeks to 32 months. In one case, the patient chronically rejected his liver graft (treated with successful retransplant) while maintaining good function in his kidney. The rate of acute rejection in the liver transplant was only 37.5% compared with 59.3% in the patients undergoing liver transplant only. There were no obvious rejections observed in the kidney transplants. These cases demonstrate the utility of simultaneous kidney-liver transplant in patients with combined kidney and liver failure. Advanced chronic renal failure should no longer be considered a contraindication to liver transplantation.

OKT3 rescue for steroid-resistant rejection in adult liver transplantation.

The results of OKT3 use for steroid-resistant rejection rescue in adult liver transplantation were analyzed retrospectively from a single transplant center. Comparison was made with concurrent patients who had no rejection (NR) or steroid-responsive rejections (SR). The records of 290 patients who underwent 323 liver transplants from April 1985 to December 1989 were examined. The first technically successful grafts were used for this analysis (265 grafts). Follow-up was a minimum of 1 year, or until death or loss of graft. All patients received triple-drug induction immunosuppression (CsA, Aza, steroids). Initial rejection was treated with 1 g methylprednisolone bolus i.v., followed by a 5-day taper of steroids from 200 mg to 20 mg. No rejection occurred in 108 (40.8%) and SR in 86 (32.4%), and OKT3 was given for persistent rejection in 71 (26.8%). The age, sex distribution, mean follow-up, and preoperative status were similar in all three groups. The preoperative diagnoses were similar, except for fulminant liver failure, in which 19 of 20 patients experienced rejection (P < 0.0001). The median hospitalization stay was 37 days for OKT3, 27 days for SR, and 21 days for NR (P < 0.0001). The median ICU stay was similar in the three groups (OKT3, 4; SR, 4; NR, 3). Infections in the first 6 weeks, and in the period of 6 weeks to 1 year posttransplant, were of similar frequency for all three groups. By the Kaplan-Meier estimation, the graft and patient actuarial survival rates were comparable. At 1 year, the graft survival rate was 79.6% for NR, 79.8% for SR, and 67.6% for OKT3. The 1-year patient survival rate was 85.2% for NR, 83.7% for SR, and 84.5% for OKT3. Following treatment by OKT3, rejection was permanently reversed in 42 patients. A temporary response occurred in 12 patients, 16 patients failed to respond to OKT3, 2 patients died during therapy, and 6 of the nonresponders died within 12 months. Additional OKT3 treatment was attempted in 6 patients for persistent rejection within a 1-month interval from the previous OKT3 course. Of these 6, 4 developed lymphoproliferative disorder, and only 1 survived in response to drastic reduction of immunosuppression. In conclusion, OKT3 was effective as rescue therapy for adult liver transplant steroid-resistant rejection. Because of the associated morbidity and expense, OKT3 should be used in a selective fashion. Failure to respond to OKT3 is a serious complication, and should not be managed by prolonged or repeated courses, but rather by alternative means.

Causes of late graft loss after liver transplantation.

The causes of graft loss in liver transplant recipients with a graft functioning for more than 1 year post-transplant were analyzed. Of 500 liver transplants in 434 patients, 362 grafts were functioning for more than 1 year. After 1 year, 42 grafts were later lost (11.6%). Thirty-three grafts were lost by death and 9 retransplants were done with 8 patients. Of the grafts lost by death, 12 had no evidence of dysfunction. The actuarial 2- and 5-year graft survival in liver transplantation recipients with functioning grafts for more than 1 year was 91 and 83%, respectively. The graft loss rate was 3.4 times higher during the 2nd year post-transplant than during 2-5 years post-transplant. The most common causes of graft loss were chronic rejection (26.2%), recurrent hepatitis (23.8%), arterial thrombosis/stenosis (11.9%) and recurrent malignancy (9.5%). No graft was lost from acute rejection. There was no difference in timing of the graft lost between the different causes. The pretransplant diagnosis of hepatitis B, chronic rejection, and malignancy was associated with the highest frequency of late graft lost. In conclusion, long-term graft survival is good after liver transplantation in patients with a functioning graft for more than 1 year. The main causes of graft loss were chronic rejection and recurrent hepatitis. Prevention and treatment for these conditions may further improve the results after liver transplantation.

Impact of pretransplant renal function on survival after liver transplantation.

To determine the effect of pretransplant liver function on survival following orthotopic liver transplantation and to quantify the effects of cyclosporine administration on long-term renal function in patients undergoing liver transplant, we performed an analysis of a prospectively maintained database. Data from 569 consecutive patients undergoing liver transplantation alone who were treated with CsA for immunosuppression were used for this study. Actuarial graft and patient survival rates were calculated using Kaplan-Meier statistics. Glomerular filtration rates, serum creatinine, and the use of various immunosuppressives were analyzed for this study. The initial analysis demonstrated that patients presenting for liver transplant with hepatorenal syndrome have a significantly decreased acturial patient survival after liver transplant at 5 years compared with patients without hepatorenal syndrome (60% vs. 68%, P < 0.03). Patients with hepatorenal syndrome recovered their renal function after liver transplant. Patients who had hepatorenal syndrome were sicker and required longer stays in the intensive care unit, longer hospitalizations, and more dialysis treatments after transplantation compared with patients who did not have hepatorenal syndrome. The incidence of end-stage renal disease after liver transplantation in patients who had hepatorenal syndrome was 7%, compared with 2% in patients who did not have hepatorenal syndrome. To more fully examine the effect of pretransplant renal function on posttransplant survival, the non-hepatorenal syndrome patients were divided into quartiles depending upon their pretransplant renal function. The patients with the lowest pretransplant renal function had the same survival as the patients with the highest pretransplant renal function. In addition, there was no increased incidence of acute or chronic rejection in any of the groups. The patients with the lower pretransplant renal function were treated with more azathioprine to maintain renal function and had a negligible decrease in glomerular filtration rate following transplant. Conversely, patients with the highest level of renal function pretransplant had a 40% decline in renal function in the first year, but maintained stable renal function up to 4 years after transplant. We conclude that pretransplant renal function other than hepato-renal syndrome has no effect on patient survival after orthotopic liver transplant. Renal function after liver transplant is stable after an initial decline, despite continued administration of CsA.(ABSTRACT TRUNCATED AT 400 WORDS)

Quality of life improvements at one, two, and five years after liver transplantation.

We prospectively studied adult liver transplant (OLTX) recipients to evaluate the effect of OLTX on quality of life (QOL). Over an 8-year period, all adult patients undergoing OLTX at our institution were asked to complete a psychological questionnaire that probed broad facets of QOL. Patients seen for their 1, 2, and 5 or more-year post-OLTX visits were also asked to complete the form. Questions were then grouped by categories broadly highlighting self-image (SI), health perception (HP), ability to function (F), and ability to work (W). Questions ranged from demographic and occupational topics to symptom distress/frequency, activities of daily living, and the impact of health on daily life. Numerical scores were assigned to each question, and added to derive scores on SI, HP, and F. Higher scores reflect better QOL. Employment data (W) were also compared, though not amenable to scoring. A total of 573 forms were completed (210 pretransplant, 150 at 1 year, 131 at 2 years, 79 at 5 years). All posttransplant scores were significantly higher than pretransplant ones (P < or = .0001, ANOVA). Scores at posttransplant time points were not significantly different from each other. Subscores of SI and HP revealed less symptom frequency and distress following OLTX (P < or = .0003) continuing to beyond 5 years. Health limitations on activities decreased both at 1 year post-OLTX and again at 2 years (P < or = .0001) and were sustained to beyond 5 years. Fewer people were working for pay at 1 year post-compared with pre-OLTX, but pre-OLTX levels of employment had been regained by the second year, continuing to increase to beyond 5 years. OLTX leads to improved QOL by the end of the first posttransplant year, sustained through the 5th posttransplant year and beyond. Self-image, functioning ability, and perception of health status were significantly improved. Ill health interference in daily life continues to decrease as OLTX becomes more remote. Employment suffers early after OLTX, but recovers by the second post-OLTX year and continues to increase long-term.

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.

Hepatorenal syndrome: combined liver kidney transplants versus isolated liver transplant.

BACKGROUND: As many as 38% of combined liver-kidney transplant (LKTx) procedures performed nationally may be done for the renal diagnosis of hepatorenal syndrome (HRS). This study was designed to compare the national results with those at our medical center and to determine if combined LKTx provides any benefit over isolated liver transplant (LTx) to HRS patients. METHODS: Data on 29 combined LKTx and 79 HRS patients at our center were collected and compared with the national data on 414 LKTx and 2442 patients with serum creatinine >2.0 mg/dl receiving isolated LTx from 1988 to 1995. RESULTS: United Network of Organ Sharing data revealed 5-year patient survival of 62.2% for LKTx recipients and 50.4% for patients with serum creatinine >2.0 mg/dl receiving isolated LTx (P=0.0001). Our center results demonstrated 5-year patient survival of 48.1% for LKTx patients, 67.1% for HRS patients receiving isolated LTx, and 70.1% for patients with serum creatinine >2.0 mg/dl receiving isolated LTx (P not significant comparing all groups). Intensive care unit status and preoperative dialysis rates were similar in those HRS patients who did and those who did not need future KTx. CONCLUSION: National data would suggest a survival benefit of combined LKTx over isolated LTx for those patients with poor renal function, specifically those with HRS, whereas our center's results suggest otherwise. Unfortunately, we could not identify any preoperative risk factors in the HRS patients, or in the broader group of patients with renal insufficiency at our center, that would indicate the need for future renal transplantation. We believe that HRS patients can be successfully managed with isolated LTx.

Ten years of liver transplantation: an evolving understanding of late graft loss.

BACKGROUND: We undertook this study to understand the causes of late graft loss and long-term outcome in orthotopic liver transplantation (OLT) recipients. METHODS: Prospectively collected data of 1174 consecutive OLT in 1045 adult patients who received liver grafts between April 1985 and August 1995 were reviewed. The causes of graft loss, pretransplant patient characteristics, and posttransplant events were analyzed in patients who survived at least 1 year after OLT, in an attempt to establish a link between these factors and graft loss. RESULTS: One hundred fifty-nine (17.9%) grafts were lost after the first year. Of these, 132 grafts were lost by death and 27 by retransplantation. Recipients who survived the first year (n=884) had 5- and 10-year survivals of 81.4% and 67.2%, respectively. Death with a functioning graft occurred in 97 (61%) patients. The main causes of late graft loss were recurrent disease (n=48), cardiovascular and cerebral vascular accidents (n=28), infections (n=24), and chronic rejection (n = 15). Pretransplant heart disease and diabetes were found to be significant risk factors for late graft loss due to cardiovascular diseases and cerebral vascular accidents. CONCLUSIONS: Survival of OLT patients who live beyond the first posttransplant year is excellent. Some patient characteristics may be associated with late graft loss. Compared with previous reports, this study shows an increased incidence of late graft loss secondary to recurrent diseases, de novo malignancies, cardiovascular diseases, and cerebral vascular accidents. Chronic rejection seems to be a less frequent cause of late graft loss. The prevention of recurrent disease and better immunosuppression may further improve these results.

A comparison of UW with Eurocollins preservation solution in liver transplantation.

Fifty consecutive liver transplants were performed using livers perfused with and stored in University of Wisconsin preservation solution. These grafts were compared with the preceding 55 consecutive transplants performed using livers perfused and preserved with Eurocollins solution. The purpose of the study was to determine if organs preserved with UW solution functioned better after transplantation than organs preserved with Eurocollins. Extensive retrospective analysis of prospectively accumulated data included enzyme levels through 30 days, cost and length of hospital stay, blood product usage, and ischemia time. Average age of patients in the UW group was 47.1 years compared with 39.6 years in the EC group (P less than 0.05); cold ischemia time was 7.21 hr in the UW group compared with 5.21 in EC (P = 0.0001). Total bilirubin values were significantly lower on days 0-6 and day 14, but not day 30, in the UW group. Aspartate aminotransferase was significantly lower in the UW group on days 0-1, 3-6, and 14, but not on day 3 or day 30. Prothrombin times were significantly lower in the UW group across all times (days 0-6, 14, and 30). Intraoperative and postoperative use of packed red blood cells and fresh frozen plasma was lower in the UW group (P less than or equal to .05). Also, total hospital days, intensive care unit days, and hospital cost to the patient were lower in the UW group (P less than or equal to .05). A second analysis was done comparing only nonemergent transplants from both groups. These results confirmed the initial analysis of a longer cold ischemia time in the UW group (P less than 0.001), and improved enzyme values in the TBR, AST, and PT in the UW group (P less than 0.05). Also, hospital cost in the UW group was again lower (P less than 0.05). In this nonrandomized study, the cold ischemia time was increased but kept close to that of the control group. We conclude that UW solution is an improved donor liver preservation solution on the basis of improved enzyme values, decreased blood usage, shorter hospital stay, and lower hospital charges.

Long-term outcome of patients transplanted with livers from hepatitis C-positive donors.

BACKGROUND: The use of hepatitis C serology-positive donors has become an option in patients affected by hepatitis C (Hep C) end-stage liver disease. Previous studies with less than 1 year of follow-up have suggested that there is no difference in early patient and graft survival. The aim of our review is to confirm with a longer follow-up (a minimum of 1 year) that the use of these organs is safe and that patient and graft survival are comparable to those of patients with Hep C who received Hep C-negative grafts. METHODS: Between 1985 and 1995, 213 patients were transplanted with a diagnosis of Hep C. Seventy-six patients were excluded from the study, 47 for insufficient follow-up and 29 because the diagnosis of recurrence was not certain. Twenty-two patients received Hep C+ donor grafts and 115 patients received Hep C-donor grafts. These two groups were evaluated to assess the rate and severity of recurrence by serial biopsies and to assess patient and graft survival. RESULTS: Recurrent Hep C was documented by biopsy in 12 of 22 patients who received Hep C+ donor grafts. Of these 12 patients, 9 had mild chronic hepatitis, 2 had fibrosis, and 1 had cirrhosis. Ten of the 22 patients had normal biopsies. Of the patients who received Hep C- grafts, 48 of 115 had recurrent disease. Of these 48 patients, 23 had mild chronic hepatitis, 15 had fibrosis, and 10 had cirrhosis. Sixty-seven of 115 had normal biopsies. The recurrence rate was 54.55% in the Hep C+ donor grafts and 41.74% in the Hep C- donor grafts (P=NS). Patient and graft survival at 4 years after transplant were 83.9% and 71.9% in the Hep C+ donor grafts and 79.1% and 76.2% in the Hep C- donor grafts, respectively (P=NS). CONCLUSIONS: Our study suggests that Hep C+ donors can be used with excellent long-term results and that the progression of the recurrent disease does not seem to be affected by the pre-existence of the Hep C virus in the donor.

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.

Hepatic artery stenosis after liver transplantation--incidence, presentation, treatment, and long term outcome.

Little is known about hepatic artery (HA) patency and patient clinical course when the nonthrombosed HA has been revised. We undertook this study to evaluate the risk factors in the development of HA stenosis and to assess the impact of HA revision on the outcome. A total of 857 adult consecutive OLT in 780 patients performed over a 6-year period were studied. Patients who underwent revision of their nonthrombosed but stenotic HA were reviewed for patient/graft survival, method of HA revision, incidence of biliary strictures, and long-term HA patency. Overall 39 patients (5%) with 41 allografts underwent HA revision for stenosis. Median time to diagnosis was 100 days posttransplant (range 1-1220 days). HA flow at the time of OLT was found to be the only significant variable of an anastomotic stenosis. No risk factor could be identified for the graft HA stenosis. Treatment methods included resection of the stenotic segment with primary reanastomosis (n = 17), aortohepatic iliac artery graft (n = 11), interposition vein graft (n = 4), vein patch angioplasty (n = 2), interposition artery graft (n = 1), and percutaneous transluminal balloon angioplasty (n = 6). Postrevisional HA patency was demonstrated in 32 (78%) cases. At a median follow-up of 25 months, 26 patients (67%) were asymptomatic with good liver function. Nine patients had developed biliary strictures. Seven patients had undergone retransplantation and 8 patients had died. The actuarial patient and graft survivals at 4 years in the patients with revised HA were 65% and 56%, respectively. HA stenosis requiring revision is an infrequent occurrence after OLT. Long-term patency of the revised HA is good. Revision of the HA may help prevent biliary strictures and allow for good long-term graft function in the majority of patients.

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.

The influence of preservation injury on rejection in the hepatic transplant recipient.

The records of 215 liver transplant recipients were reviewed and the degree of preservation injury was estimated by the initial aminotransferase levels. This was compared with the incidence of rejection found in the subsequent 30 days. Those with aspartate aminotransferase greater than 2000 U/L were classified as having severe preservation injury while those with ASAT less than 600 U/L were considered to have had minimal preservation injury. There were no significant differences between these groups in recipient age, sex, cold ischemia time, preoperative physical status, panel-reactive antibodies, or cytotoxic crossmatch. The solution used for organ preservation and the donor age were the only factors that were found to be significantly different between the groups. Older donors were more common in the severe preservation injury group. Severe preservation injury was found more frequently in grafts preserved in Eurocollins solution and the group with minimal preservation injury more frequently used Wisconsin solution. There was significantly more rejection seen in the severe preservation injury group (71%) than in the group without preservation injury (33%). Although there was more rejection in the severe preservation injury group, the rejections were not more severe as judged by the need for multiple courses of therapy or the need for OKT3. Recurrent rejection was also not more frequent in either group. Graft survival was worse in the severe preservation injury group, with a significant increase in early graft loss, but no difference in the frequency of chronic rejection. Recovery of graft function was also delayed in the preservation injury group.