G. Klintmalm

Nonalcoholic fatty liver disease after liver transplantation for cryptogenic cirrhosis or nonalcoholic fatty liver disease

Nonalcoholic steatohepatitis (NASH) may account for many cases of cryptogenic cirrhosis. If so, then steatosis might recur after liver transplantation. Two thousand fifty‐two patients underwent primary liver transplantation for chronic liver disease between 1986 and 2004. Serial liver biopsy samples were assessed for steatosis and fibrosis. Two hundred fifty‐seven patients (12%) had a pretransplant diagnosis of cryptogenic cirrhosis (239) or NASH (18). Fatty liver developed in 31% and was more common when the pretransplant diagnosis was NASH (45% at 5 years versus 23% for cryptogenic cirrhosis, P = 0.007). NASH developed in only 4% and occurred exclusively when steatosis had already occurred. Steatosis after liver transplantation was associated with the baseline body weight and body mass index by univariate analyses, but no pretransplant or posttransplant characteristic independently predicted steatosis after liver transplantation because obesity was so common in all groups. Five percent and 10% developed bridging fibrosis or cirrhosis after 5 and 10 years, respectively, and this was more common after NASH (31%) than in those who developed steatosis alone (6%) or had no fat (3%, P = 0.002). One‐, 5‐, and 10‐year survival was the same in patients who underwent transplantation for cryptogenic cirrhosis or NASH (86%, 71%, and 56%) and in patients who underwent transplantation for other indications (86%, 71%, and 53%; not significant), but death was more often due to cardiovascular disease and less likely from recurrent liver disease. In conclusion, fatty liver is common after liver transplantation for cryptogenic cirrhosis or NASH but is twice as common in the latter group; this suggests that some cryptogenic cirrhosis, but perhaps not all, is caused by NASH. Posttransplant NASH is unusual, and steatosis appears to be a prerequisite. Advanced fibrosis is uncommon, and survival is the same as that of patients who undergo transplantation for other causes. Liver Transpl 16:431‐439, 2010.

Impact of sirolimus on the recurrence of hepatocellular carcinoma after liver transplantation

Tumor recurrence after liver transplantation for hepatocellular carcinoma is associated with a poor prognosis. Because immunosuppression is a well‐known risk factor for tumor growth, it is surprising that its possible role in the outcome of liver transplantation has been poorly evaluated. We performed a case‐control review of prospectively collected data and compared 2 groups of patients according to the type of immunosuppression after liver transplantation for hepatocellular carcinoma at a single center. One hundred six patients received tacrolimus and mycophenolate mofetil, and 121 received sirolimus. Patients in the sirolimus group had significantly higher recurrence‐free survival rates than patients in the tacrolimus group (P = 0.0003). The sirolimus group also had significantly higher patient survival rates than the tacrolimus group at 1 year (94% versus 79%), 3 years (85% versus 66%), and 5 years (80% versus 59%; P = 0.001). Sirolimus was well tolerated, and the patients in this study did not have the increase in surgical complications noted by other investigators. Leukopenia was the most common side effect, but it typically resolved with dose reduction. Dyslipidemia and mouth ulcers were common but were easily controlled. In summary, the data suggest a beneficial effect of sirolimus immunosuppression on recurrence‐free survival, which translates into patient survival benefits. Liver Transpl 15:1834–1842, 2009.

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.

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.

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

OBESITY AS AN ADVERSE FACTOR FOR SURVIVAL IN SICK LIVER TRANSPLANT RECIPIENTS (MELD>25): 1216

N. Onaca1, S. Chinnakotla2, G.J. McKenna2, R. Ruiz3, M. Asolati2, P. Kim2, K. Cavaness2, K. Tomiyama3, B. Yildiz2, R. Goldstein2, M.F. Levy1, G. Klintmalm4 1Islet Cell Transplant Program, Baylor Regional Transplant Institute, Dallas/UNITED STATES OF AMERICA, 2Transplant Services, Baylor Regional Transplant Institute, Dallas/TX/UNITED STATES OF AMERICA, 3Transplant Surgery, Baylor University Medical Center, Dallas/Texas/UNITED STATES OF AMERICA, 4, Baylor University Medical Center, Dallas/UNITED STATES OF AMERICA