Jonathan A. Fridell

Use of extended criteria livers decreases wait time for liver transplantation without adversely impacting posttransplant survival.

Introduction:The use of extended criteria donors (ECDs) could minimize shortage of suitable donor livers for transplantation. In 3 years, the aggressive use of ECD livers has reduced the wait list at our center from 257 to 30 patients with a median wait time of 18 days without using living donors. This study compares the graft/patient survival from standard (SD) and ECD for our transplant population between 2001 and 2005. Methods:Records of all adult liver transplant recipients over 4 years were reviewed (n = 571). ECD criteria included: age >59 years, BMI >34.9, maximum AST/ALT >500, maximum bilirubin >2.0, peak serum sodium >170, HBV/HCV/HTLV reactive, donation after cardiac death, cold ischemia time >12 hours, ICU stay >5 days, 3 or more pressors simultaneously, extensive alcohol abuse, cancer history (nonskin), active meningitis/bacteremia, or significant donor liver trauma. Outcomes included graft and patient survival at 90 days, 1 year, and 2 years. Results:Sixty-eight percent of recipients (n = 388) received ECD livers. Primary factors accounting for ECD-liver status included: elevated liver function tests (20%), hypernatremia (12.6%), and extensive alcohol abuse (11.4%). Graft survival was (SD, ECD): 90-day 91%, 88%; 1-year 84%, 80%; 2-year 78%, 77%; patient survival was: 90-day 93%, 90%; 1-year 87%, 82%; 2-year 83%, 79%. Kaplan-Meier survival analysis failed to demonstrate an overall difference in graft or patient survival at any time point. Only donor age >60 years was associated with decreased graft and patient survival. Conclusions:Liver grafts from ECD can be used to dramatically reduce wait list time with outcomes comparable to those for SD without resorting to living donor liver transplantation.

Comparison of histidine‐tryptophan‐ketoglutarate solution (HTK) and University of Wisconsin solution (UW) in adult liver transplantation

Histidine‐tryptophan‐ketoglutarate solution (HTK) and University of Wisconsin solution (UW) have been shown to have similar outcomes in cadaveric kidney, pancreas, and liver transplantation. Our institution changed from UW to HTK as the primary preservation solution for liver, kidney and pancreas transplantation. This study compares the perioperative and first year outcomes of liver transplantation using UW or HTK. Primary use of HTK began on May 1, 2003. We reviewed the records of all adult liver transplant recipients from July 1, 2002 to December 31, 2004. Recipients were compared based on organ preservation solution (UW n=204, HTK n=174). Outcomes included 1‐, 6‐ and 12‐month graft and patient survival and 1‐, 7‐, 14‐, and 30‐day liver function and serum creatinine. During the entire study period, the two groups were managed similarly in operative technique, immunosuppressive regimens, and donor liver criteria. Over 30 months, 378 adult patients underwent liver transplantation. There were no significant differences between UW and HTK in 1‐, 6‐, or 12‐month graft or patient survival. The HTK group had a higher day 1 median AST, ALT, and total bilirubin, but the two groups were similar thereafter. An anticipated difference in infused volume between UW and HTK was demonstrated. In conclusion, to our knowledge, this is the first reported large case series from North America comparing HTK and UW in liver transplantation with 2‐ to 12‐month follow‐up. There were no significant differences between HTK and UW in this population when comparing 1 month graft function and first‐year graft and patient survival. Liver Transpl 12:226–230, 2006.

Comparison of histidine-tryptophan-ketoglutarate solution and University of Wisconsin solution for organ preservation in clinical pancreas transplantation.

Background. University of Wisconsin (UW) solution is currently the standard preservation solution used for abdominal organ transplantation. This study assesses the efficacy of histidine-tryptophan-ketoglutarate (HTK) compared with UW in pancreas transplantation. Methods. Between October 2002 and August 2003, 20 pancreas transplants were performed. Patients were divided into two groups: UW (n=10) and HTK (n=10). Donor and recipient demographics were similar in both groups. The mean cold ischemia time for both groups was 11±3 hr. Results. There was an anticipated difference between total preservative volumes used (HTK: 4.5±1.2 L vs. UW: 3.4±0.8 L; P =0.03). Patient and graft survivals to date were 100% in both groups. Serum fasting blood glucose, peak amylase, and serial amylase levels remained comparable at all intervals posttransplantation. Conclusions. Within this range of cold ischemia time, UW and HTK demonstrate similar efficacy in pancreas preservation.

Liver Transplantation in Children with Cystic Fibrosis: A Long-Term Longitudinal Review of a Single Center's Experience

BACKGROUND Improved long-term survival in cystic fibrosis (CF) has led to an increased incidence of extrapulmonary complications of this disease. Of these, end-stage liver disease is a significant cause of morbidity and mortality with liver transplantation being the only effective therapy. METHODS Records of all CF pediatric liver transplant recipients were reviewed. RESULTS Twelve children with CF were the recipients of 16 allografts. The 1- and 5-year survival was 91.6% and 75%, respectively. There were 5 deaths at a mean interval of 6.8 +/- 6.3 years. All of these deaths were related to pulmonary disease. Pulmonary function improved or remained stable in 8 of 9 patients tested. Despite an 83% incidence of positive sputum cultures, there was only one early mortality related to pulmonary sepsis in the setting of primary liver allograft nonfunction. CONCLUSIONS Liver transplantation is acceptable treatment for children with CF and end-stage liver disease. Long-term survival is comparable to liver transplantation performed for other indications. Although posttransplant morbidity and mortality is related to lung disease, the authors speculate that as therapeutic improvements prolong the survival in CF, it is expected that longer survival after liver transplantation in this patient population may also be anticipated.

Promising early results with immunosuppression using rabbit anti-thymocyte globulin and steroids with delayed introduction of tacrolimus in adult liver transplant recipients

Induction therapy with T‐cell depleting drugs in liver transplantation is controversial. This study examined the use of rabbit antithymocyte globulin (RATG) with delayed introduction of tacrolimus in liver transplant recipients. Additional subgroup analysis compared patients with or without hepatitis C (HCV) cirrhosis. Over 17 months, 116 adults received 120 liver allografts. Four patients who died before receiving RATG were excluded. Immunosuppression included steroids, 3 doses of RATG (2 mg/kg), and tacrolimus started on postoperative day 3 to 4. Ninety‐six percent of patients were alive with a mean follow‐up of 12.9±4.5 months. No graft was lost to rejection. Two patients developed hepatic artery thrombosis. Six percent of patients had acute rejection. No patient had steroid resistant or recurrent rejection. RATG related drug events were limited to fever, chills, tachycardia, and oxygen desaturation. There were no cases of lymphoproliferative disease. Forty‐two percent of patients were transplanted for HCV. Thirty‐two percent of HCV‐patients had biopsy proven hepatitis C recurrence occurring at 4 weeks to 10 months posttransplant. RATG induction therapy is associated with good patient and graft survival, a low incidence of rejection, and minimal side effects. In addition, RATG induction is safe in patients transplanted for HCV. (Liver Transpl 2004;10:404–407.)

Multivisceral transplantation for diffuse portomesenteric thrombosis

Objective:To evaluate the clinical outcomes of multivisceral transplantation (MVT) in the setting of diffuse thrombosis of the portomesenteric venous system. Background:Liver transplantation (LT) in the face of cirrhosis and diffuse portomesenteric thrombosis (PMT) is controversial and contraindicated in many transplant centers. LT using alternative techniques such as portocaval hemitransposition fails to eliminate complications of portal hypertension. MVT replaces the liver and the thrombosed portomesenteric system. Methods:A database of intestinal transplant patients was maintained with prospective analysis of outcomes. The diagnosis of diffuse PMT was established with dual-phase abdominal computed tomography or magnetic resonance imaging with venous reconstruction. Results:Twenty-five patients with grade IV PMT received 25 MVT. Eleven patients underwent simultaneous cadaveric kidney transplantation. Biopsy-proven acute cellular rejection was noted in 5 recipients, which was treated successfully. With a median follow-up of 2.8 years, patient and graft survival were 80%, 72%, and 72% at 1, 3, and 5 years, respectively. To date, all survivors have good graft function without any signs of residual/recurrent features of portal hypertension. Conclusions:MVT can be considered as an option for the treatment of patients with diffuse PMT. MVT is the only procedure that completely reverses portal hypertension and addresses the primary disease while achieving superior survival results in comparison to the alternative options.

Comparison of Histidine-Tryptophan Ketoglutarate Solution and University of Wisconsin Solution in Prolonged Cold Preservation of Kidney Allografts

Although University of Wisconsin (UW) solution is the standard preservation solution for organ transplantation, Histidine-Tryptophan Ketogluatarate (HTK) solution has been increasingly used. This study compared HTK or UW for cold static storage of kidney allografts. In all, 149 renal transplants were performed with cold ischemic times (CI) greater than 16 hr (UW 87, HTK 62) and a subset analysis was performed with CI over 24 hr (HTK 31, UW 38). Data from receiving renal transplant centers focused on delayed graft function (DGF), patient and allograft survival. In CI greater than 16 hr, graft and patient survival were comparable. HTK cohort had lower DGF. In CI greater than 24 hr, there was no difference in patient survival, a trend towards improved graft survival in HTK, and decreased rate of DGF in HTK. This data suggests that UW and HTK have at least similar efficacy in kidney preservation at longer ischemic times.

Induction Immunosuppression With Thymoglobulin and Rituximab in Intestinal and Multivisceral Transplantation

Background. Induction immunosuppression is now a common practice after intestinal and multivisceral transplantation. We report our experience in 27 adult recipients who received rituximab and rabbit antithymocyte globulin (rATG) in combination as induction agents. Material and Methods. Twenty-seven adult patients received 29 intestinal transplants between July 2004 and March 2007. All patients received induction immunosuppression therapy with rATG, rituximab, and steroids. Tacrolimums and a steroid taper were used for maintenance therapy. Patient and graft survival, episodes of rejection as well as posttransplant lymphoproliferative disease (PTLD) and graft-versus-host disease were analyzed. Results. One-year patient and graft survival was 81% and 76%, respectively. Thirteen patients (48%) experienced 19 episodes of acute rejection (9 mild episodes, 2 moderate, and 8 severe). Patients with a multivisceral graft experienced less episodes of severe acute rejection (1 of 19, 5%) when compared with isolated intestinal transplants and modified multivisceral transplants (7 of 10, 70%). Two patients had episodes of skin graft-versus-host disease that responded to steroid boluses. PTLD was not seen in our series. Two patients developed cytomegalovirus enteritis. Conclusions. The combination of rATG and rituximab was an effective induction therapy in our preliminary data. The number and severity of rejection episodes increased when the liver was not included as part of the graft. An immunosuppression regimen including rATG, rituximab, and steroids may have a protective effect against PTLD and chronic rejection.

Immunosuppression induction with rabbit anti‐thymocyte globulin with or without rituximab in 1000 liver transplant patients with long‐term follow‐up

Rabbit anti‐thymocyte globulin (rATG)–based immunosuppression induction is being increasingly used in liver transplantation (LT) in conjunction with steroid‐free protocols to delay the initiation of calcineurin inhibitors. This study reports a single‐center comparison of transplant outcomes and complications in 3 immunosuppression eras. Data were obtained retrospectively from a center research database, and the analysis included LT patients from 2001 to 2008. The immunosuppression consisted of rATG induction in 3 doses (6 mg/kg in all): (1) the first dose was administered perioperatively [the rabbit anti‐thymocyte globulin in the operating room (rATG‐OR) era]; (2) the first dose was delayed until 48 hours after transplantation [the rabbit anti‐thymocyte globulin after a delay (rATG‐D) era]; or (3) the first dose was delayed until 48 hours after transplantation, and a single dose of rituximab was added 72 hours after transplantation [the rabbit anti‐thymocyte globulin after a delay plus rituximab (rATG‐D‐Ritux) era]. The initial maintenance immunosuppression was tacrolimus monotherapy, which was started on postoperative day 2. There were 166 patients (16%) in the rATG‐OR era, 259 patients (26%) in the rATG‐D era, and 588 patients (58%) in the rATG‐D‐Ritux era (1013 patients in all). Demographically, the latter eras were characterized by higher recipient and donor ages; greater percentages of liver‐kidney transplants, hepatocellular carcinoma (HCC), donation after cardiac death (DCD), and imported organs; and shorter graft ischemia times. There were no significant differences between the 3 immunosuppression groups in unadjusted patient survival 3 and 5 years after transplantation (80% and 75% for the rATG‐OR era, 75% and 67% for the rATG‐D era, and 79% and 71% for the rATG‐D‐Ritux era, P = 0.15). The 5‐year survival rates for patients with hepatitis C virus (HCV) and HCC were 65% and 68%, respectively. The factors included in the Cox regression model for patient death included the Model for End‐Stage Liver Disease score [hazard ratio (HR) = 1.03, P = 0.001], HCV (HR = 1.28, P = 0.04), donor age (HR = 1.01, P = 0.001), recipient age (HR = 1.01, P = 0.05), and DCD (HR = 1.55, P = 0.11). rATG‐based induction immunosuppression can be safely used in adult LT recipients with excellent survival and low rejection rates and without increases in immunosuppression‐related side effects. Liver Transpl, 2012.

The pancreas allograft donor: current status, controversies, and challenges for the future

Fridell JA, Rogers J, Stratta RJ. The pancreas allograft donor: current status, controversies, and challenges for the future.
Clin Transplant 2010: 24: 433–449.
© 2010 John Wiley & Sons A/S.