Osman Abbasoglu

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.

Recurrent Primary Sclerosing Cholangitis After Orthotopic Liver Transplantation: Is Chronic Rejection Part of the Disease Process?

BACKGROUND The possibility of primary sclerosing cholangitis (PSC) recurrence after liver transplantation has been debated. The aim of this study is to examine whether recurrent PSC and chronic rejection (CR) are different expressions of the same disease process. METHODS One hundred consecutive patients receiving 118 grafts for the diagnosis of PSC were reviewed and placed into three groups: group A, recurrent disease, as evidenced by cholangiographic and pathologic findings with radiographic arterial flow to the liver (n=18; 15.7%); group B, those who developed CR (n=15; 13.0%); and group C, all others (n=82; 71.3%). Cholangiograms and histopathologic specimens were examined in a blinded fashion. RESULTS Demographic factors were similar, except for age, with a significantly younger age and more episodes of rejection in groups A and B (P<0.03). Group A had a higher incidence of cytomegalovirus hepatitis (P=0.008). Five-year graft survivals for A, B, and C were 64.6%, 33.3%, and 76.1%, respectively (P=0.0001), 5-year patient survivals were 76.2%, 66.7%, and 89.1%, respectively (P=0.0001), and repeat transplantation rates were 27.8%, 46.7%, and 8.5%, respectively (P=0.005). Radiographically, 90% of cholangiograms in patients with recurrent disease showed at least multiple intrahepatic strictures. Histopathologically, patients with recurrent disease and CR shared many features. CONCLUSIONS We have described a high incidence of recurrent PSC and CR in patients who received transplants for PSC. Histopathologic analysis suggests that CR and recurrent PSC could represent a spectrum of indistinguishable disease. However, the distinct difference in clinical outcome, as evidenced by an increased repeat transplantation rate and lower graft and patient survival in the CR group, clearly suggests that they are two distinct entities that require very different treatment strategies.

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 centers 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.

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 (l0%) 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.

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.

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.

DOES INTRAOPERATIVE HEPATIC ARTERY FLOW PREDICT ARTERIAL COMPLICATIONS AFTER LIVER TRANSPLANTATION

BACKGROUND Little is known about the value of intraoperative hepatic artery (HA) flow measurement on the development of HA complications in orthotopic liver transplantation (OLT). We undertook this study to see whether assessing HA flow at the OLT helps predict posttransplant HA complications (HA thrombosis or stenosis). METHODS Four hundred and eleven consecutive OLT in 367 adult patients who received grafts between November 1992 and August 1995 were reviewed. Of these, 259 grafts in 255 patients with at least 1 year of follow-up and with complete data were studied. HA flow, portal vein flow, percentage of cardiac index going to HA (HA/CI), HA flow per 100 g of liver tissue, mean arterial pressure, central venous pressure, and CI were analyzed. Preservation injury was assessed by posttransplant alanine aminotransferase and aspartate aminotransferase levels. RESULTS Thirty-four patients with 35 grafts developed HA thrombosis or stenosis during a median follow-up time of 29 months. HA complications occurring within the first 100 days of OLT were classified as early complications. HA flow at the time of surgery and percentage of CI going to the liver were found to be significant variables in early HA complications. Hepatic hemodynamics were not different in the late HA complication group compared to the control. Systemic hemodynamics and posttransplant alanine amino-transferase and aspartate aminotransferase levels were similar in all three groups. Logistic regression analysis showed that patients with HA flows less than 400 ml/min were more than 5 times as likely to develop HA complications (risk ratio 5.1). CONCLUSIONS HA flow measurement should be obtained at the time of OLT and may help to predict early but not late posttransplant HA complications. Patients with HA flows less than 400 ml/min or HA/CI values of less than 7% may carry a higher risk for HA stenosis or thrombosis and may need close surveillance to detect such problems.

The Safety of Cardiac Operations in the Liver Transplant Recipient

BACKGROUND Advances in surgical techniques and immunosuppressive drugs have improved the survival of patients after orthotopic liver transplantation. Enhanced survival has resulted in an increased number of patients who require medical as well as surgical management of diseases. METHODS To contribute to the sparse literature on the surgical aspects, we reviewed our experience with 15 patients who underwent cardiac operation (1.25%) from a total of 1,200 liver transplant recipients at our center. The variables studied included the pretransplant cardiac evaluation, the interval from transplantation to cardiac operation, postoperative complications, the management of immunosuppression, and follow-up. The patients had a mean age of 52.9 years (range, 39 to 69 years) and 13 of them (86.6%) were men. Multiple cardiac risk factors were present in all 15 patients and chronic renal insufficiency was present in 7 patients. Cardiac operation was undertaken a mean of 30.4 months (range, 9 days to 62 months) after myocardial ischemia and valvular regurgitation had been ruled out at the time of transplantation. Myocardial revascularization was performed in 12 patients, 2 of whom underwent concurrent valve operation and 3 of whom underwent valve repair or replacement. Most patients had their immunosuppression regimen continued at baseline levels. RESULTS There were no early deaths. Three patients had major complications and 4 had minor complications. There were no bleeding, infection, or healing complications. Postoperative renal parameters were persistently elevated in 5 patients and transiently elevated in 3. Liver function parameters were transiently elevated in 6 patients after the cardiac operation. No patient had hepatic rejection. A transient elevation or decrease in immunosuppressive drug levels was seen in 3 patients. Follow-up, obtained on all 15 patients, ranged from 6 to 83 months (mean, 26.5 months). There were 2 late deaths (13.3%), and 3 patients (25%) who underwent myocardial revascularization had recurrent angina. CONCLUSIONS Cardiac operations can be undertaken safely in liver transplant recipients with good intermediate-term results. The immunosuppression regimen can be continued at preoperative levels with no need for stress-dose steroids. There were no hepatic complications among our patients, although some patients can experience worsening of renal failure.

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.