Search

The disparity between the number of available renal donors and the number of patients on the transplant waiting list has prompted the use of expanded-criteria-donor (ECD) renal allografts to expand the donor pool. ECD allografts have shown good results in appropriately selected recipients, yet a number of renal allografts are still discarded. The use of dual renal transplantation may lower the discard rate. Additionally, the use of perfusion systems may improve acute tubular necrosis rates with these allografts. We report a successful case of a dual transplant with ECD allografts using a perfusion system. The biopsy appearance and the pump characteristics were suboptimal for these kidneys, making them unsuitable for single transplantation; however, the pair of transplanted kidneys provided increased nephron mass and functioned well. We recommend that ECD kidneys that are individually nontransplantable be evaluated for potential dual renal transplantation. Biopsy criteria and perfusion data guidelines must be developed to improve the success rates with ECD dual renal allografts. Finally, recipient selection is of utmost importance. [ABSTRACT FROM AUTHOR]

Vascular thrombosis is a cause of allograft loss after pancreas transplantation. We present the use of intraoperative fluorescence imaging with the SPY imaging device (Novadaq Technologies Inc, Toronto, Canada) in two pancreas transplants as a means to assess potency of the vascular anastomoses. Intravenous indocyanine green 2.5 mg/mL was fluoresced with the device to create the intraoperative video sequences, which were recorded. After 60-day follow-up, real-time SPY imaging on these two pancreas transplants did not demonstrate adverse effects on patients or the transplanted allografts. This method of vascular imaging could prove useful in improving short-term graft survival and possibly lowering the thrombosis rates seen with pancreas transplantation. Long-term correlation studies between intraoperative findings and graft survival must be performed to confirm the utility of this imaging method. [ABSTRACT FROM AUTHOR]

Biliary intraepithelial neoplasm (BilIN) and intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) are recognized as the two main precursors to biliary carcinoma. Surgical resection is the mainstay of treatment, with pancreaticoduodenectomy for extrahepatic biliary duct disease involving the pancreatic or distal portion of the bile duct, and bile duct and liver resection for perihilar and intrahepatic bile duct involvement. For diffuse IPMN-B with involvement of the entirety of the biliary epithelium of both intrahepatic and extrahepatic biliary systems, there is no well-documented consensus on treatment due to its rarity. Therefore, we present a case of a 56-year-old male with diffuse IPMN-B managed with combined orthotopic liver transplant and pancreaticoduodenectomy. As such, the clinical presentation, diagnostics, and unique course of intervention for our patient are described. This case provides insight into the topic of managing IPMN-Bs, particularly with diffuse biliary tree involvement. With such a rare disease with wildly varied presentations, consensus on a set treatment algorithm is nearly impossible to establish. This case describes one treatment pathway we found to be successful., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Fang et al.)

The ultimate preferred treatment for hepatocellular carcinoma (HCC) complicated with cirrhosis and portal hypertension is an orthotopic liver transplant (OLT). Loco regional therapy (LRT) has emerged to prevent tumor growth and progression of disease beyond the Milan criteria to achieve transplant. There is a paucity of data regarding safety, posttransplant survival benefits, and tumor recurrence rate achieved by these LRT modalities. We aim to assess and compare the five-year survival rate and tumor recurrence rate with or without LRT in patients after OLT with diagnosed HCC utilizing the nation's largest dataset. This is a retrospective observational study approved by Saint Louis University institutional review board. We utilized the largest dataset from the years 2003-2013 where pertaining data were gathered from Organ Procurement Transplant Network (OPTN) standard analysis and research files (STAR) through novel linkages with Medicare bills. Descriptive and comparative statistics were performed. 2412 (51.6%) patients received any form of locoregional therapy (single or combination) out of 4669 total study sample size. The overall five-year survival in the study sample was 76.1%. There was statistically no significant improvement seen in five-year posttransplant survival in the group that received one mode of LRT (adjusted hazard ratio (aHR) 0.97, P<0.64) or a combination of LRT (aHR 0.94, P<0.58) in comparison to those that received none after adjusting donor and recipient clinical characteristics. However, five-year survival trended higher among those treated with combination therapy over those treated with single LRT or none. Overall HCC recurrence was 4.8%, while no significant difference was noted when comparing above-mentioned groups. Five-year posttransplant survival and HCC recurrence rate were also found to have no difference when compared between above-mentioned groups after adjusting explant pathology. This is the largest retrospective study comparing liver transplant patients with HCC who received LRT to none. Although it did not show any statistically significant benefit of single or combination of LRT on survival or tumor recurrence after liver transplant for HCC patients, the outcomes encourage the safe and feasible use of LRT as a bridging therapy. Our study also suggests an observed pattern of improved posttransplant survival and tumor recurrence rate with combination loco-regional therapy. Larger multicenter prospective studies will be required to achieve the effect size to determine the best therapies for maximizing patient survival cost-effectively., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Desai et al.)

Background: With the introduction of direct-acting antiviral therapies (DAAs), the non-use rate of hepatitis C virus (HCV)-positive donor organs (D+) has decreased significantly. We present the donor, recipient, and transplant allograft characteristics, along with recipient outcomes, in one of the largest cohorts of HCV-D+ transplants into HCV-naïve recipients (R-)., Methods: Charts of HCV D+/R- kidney (KT), liver (LT), and simultaneous liver-kidney (SLKT) transplant recipients between January 2019 and July 2022 were reviewed. Primary outcomes of interest included waitlist times and 1-year graft failure. Secondary outcomes included hospital and intensive care unit length of stay, post-transplant complications, effectiveness of DAA therapy, and characteristics of patients who relapsed from initial DAA therapy., Results: Fifty-five HCV D+/R- transplants at our center [42 KT (26 nucleic acid testing positive [NAT+], 16 NAT-), 12 LT (eight NAT+, four NAT-), and one SLKT (NAT+)] had a median waitlist time of 69 days for KT, 87 days for LT, and 15 days for SLKT. There were no graft failures at 1 year. All viremic recipients were treated with a 12-week course of DAAs, of which 100% achieved end of treatment response (EOTR)-85.7% (n = 30) achieved sustained virologic response (SVR) and 14.3% relapsed (n = 5; four KT, one LT). All relapsed recipients were retreated and achieved SVR. The most common post-transplantation complications include BK virus infection (n = 9) for KT and non-allograft infections (n = 4) for LT., Conclusions: Our study has demonstrated no graft failures or recipient deaths at 1 year, and despite a 14.3% relapse rate, we achieved 100% SVR. Complications rates of D+/R- appeared comparable to national D-/R- complication rates. Further studies comparing D+/R- to D-/R- outcomes are needed., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Although the population of older transplant recipients has increased dramatically, there are limited data describing the impact of immunosuppression regimen choice on outcomes in this recipient group., Methods: National data for US Medicare-insured adult kidney recipients (N = 67 362; 2005-2016) were examined to determine early immunosuppression regimen and associations with acute rejection, death-censored graft failure, and mortality using multivariable regression analysis in younger (18-64 y) and older (>65 y) adults., Results: The use of antithymocyte globulin (TMG) or alemtuzumab (ALEM) induction with triple maintenance immunosuppression (reference) was less common in older compared with younger (36.9% versus 47.0%) recipients, as was TMG/ALEM + steroid avoidance (19.2% versus 20.1%) and mammalian target of rapamycin inhibitor (mTORi)-based (6.7% versus 7.7%) treatments. Conversely, older patients were more likely to receive interleukin (IL)-2-receptor antibody (IL2rAb) + triple maintenance (21.1% versus 14.7%), IL2rAb + steroid avoidance (4.1% versus 1.8%), and cyclosporine-based (8.3% versus 6.6%) immunosuppression. Compared with older recipients treated with TMG/ALEM + triple maintenance (reference regimen), those managed with TMG/ALEM + steroid avoidance (adjusted odds ratio [aOR], 0.440.520.61) and IL2rAb + steroid avoidance (aOR, 0.390.550.79) had lower risk of acute rejection. Older patients experienced more death-censored graft failure when managed with Tac + antimetabolite avoidance (adjusted hazard [aHR], 1.411.782.25), mTORi-based (aHR, 1.702.142.71), and cyclosporine-based (aHR, 1.411.782.25) regimens, versus the reference regimen. mTORi-based and cyclosporine-based regimens were associated with increased mortality in both older and younger patients., Conclusions: Lower-intensity immunosuppression regimens (eg, steroid-sparing) appear beneficial for older kidney transplant recipients, while mTORi and cyclosporine-based maintenance immunosuppression are associated with higher risk of adverse outcomes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction Resident inexperience during time-sensitive vascular anastomoses of a kidney transplant can negatively impact outcomes. In light of this, we created a low-cost bench-top kidney transplant surgery simulator to help residents practice vascular anastomoses. Methods We searched for inexpensive materials to design an iliac fossa and kidney allograft. Eighteen residents with real-life kidney transplant experience trialed the simulator and scored its fidelity and educational utility on a 0-100 visual analog scale (VAS) survey. Results A 35.9 x 19.4 x 12.4 cm plastic box mimicked the iliac fossa. Hooks attached to the box's sidewall held under tension 1.27 and 0.64 cm diameter Penrose drains to replicate the external iliac vein and artery. A modified kidney-shaped stress ball with 1.27 x 4, 0.64 x 4, and 0.64 x 15 cm Penrose drains replicated a kidney allograft with its vein, artery, and ureter, respectively. Residents performed and assisted in vascular anastomoses on the simulator. The iliac fossa and allograft cost $20.20 and each practice run cost $7.20. Residents thought that the simulator was less difficult than real-life procedure, had acceptable fidelity levels, and they highly rated its educational utility. Conclusion Our novel low-cost bench-top kidney transplant surgery simulator focusing on vascular anastomoses received positive educational feedback from residents., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Melkonian et al.)

Medicare costs vary for solid organ transplant recipients by outcome: survival with graft function, survival with graft failure, and death. Average per-person per-year reimbursement was $75 thousand for kidney recipients who survived the first year posttransplant with a functioning graft, $171 thousand for those who required a return to dialysis or retransplant, and $350 thousand for those who died with function. For pancreas recipients: $105 thousand for those who survived the first year with a functioning graft, $120 thousand for those who survived pancreas failure, and $443 thousand for those who died with function. For liver recipients: $154 thousand for those who survived with a functioning graft, $388 thousand for those who required retransplant, and $740 thousand who died with function. For intestine recipients: $301 thousand for those who survived with a functioning graft and $1 million for those who died with function. For heart recipients: $272 thousand for those who survived with a functioning graft and $1.2 million for those who died with function. For lung recipients: $196 thousand for those who survived with a functioning graft, $642 thousand for those who required retransplant, and $761 thousand for those who died with function., (.)

Background: Living donor pancreas transplant is a potential treatment for diabetic patients with end-organ complications. Although early surgical risks of donation have been reported, long-term medical outcomes in living pancreas donors are not known., Methods: We integrated national Scientific Registry of Transplant Recipients data (1987-2015) with records from a nationwide pharmacy claims warehouse (2005-2015) to examine prescriptions for diabetes medications and supplies as a measure of postdonation diabetes mellitus. To compare outcomes in controls with baseline good health, we matched living pancreas donors to living kidney donors (1:3) by demographic traits and year of donation., Results: Among 73 pancreas donors in the study period, 45 were identified in the pharmacy database: 62% women, 84% white, and 80% relatives of the recipient. Over a mean postdonation follow-up period of 16.3 years, 26.7% of pancreas donors filled prescriptions for diabetes treatments, compared with 5.9% of kidney donors (odds ratio, 4.13; 95% confidence interval, 1.91-8.93; P = 0.0003). Use of insulin (11.1% vs 0%) and oral agents (20.0% vs 5.9%; odds ratio, 4.50, 95% confidence interval, 2.09-9.68; P = 0.0001) was also higher in pancreas donors., Conclusions: Diabetes is more common after living pancreas donation than after living kidney donation, supporting clinical consequences from reduced endocrine reserve.

Characteristics of cirrhosis-associated cryptococcosis first diagnosed after death are not fully known. In a multicenter study, data generated as standard of care was systematically collected in 113 consecutive patients with cirrhosis and cryptococcosis followed for 80 patient-years. The diagnosis of cryptococcosis was first established after death in 15.9% (18/113) of the patients. Compared to cases diagnosed while alive, these patients had higher MELD score (33 vs. 22, P = .029) and higher rate of cryptococcemia (75.0% vs. 41.9%, P = .027). Cases diagnosed after death, in comparison to those diagnosed during life were more likely to present with shock (OR 3.42, 95% CI 1.18-9.90, P = .023), require mechanical ventilation at admission (OR 8.5, 95% CI 2.74-26.38, P = .001), less likely to undergo testing for serum cryptococcal antigen (OR 0.07, 95% CI 0.02-0.21, P < .001) and have positive antigen when the test was performed (OR 0.07, 95% CI 0.01-0.60, P = .016). In a subset of cirrhotic patients with advanced liver disease cryptococcosis was first recognized after death. These patients had the characteristics of presenting with fulminant fungemia, were less likely to have positive serum cryptococcal antigen and posed a diagnostic challenge for care providers., (© The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Implications of prescription opioid use for outcomes after liver transplantation (LT) have not been described. We integrated national transplant registry data with records from a large pharmaceutical claims clearinghouse (2008-2014; n = 29,673). Opioid fills on the waiting list were normalized to morphine equivalents (MEs), and exposure was categorized as follows: > 0-2 ME/day (level 1), > 2-10 ME/day (level 2), > 10-70 ME/day (level 3), and >70 ME/day (level 4). Associations (adjusted hazard ratio [aHR], 95% LCL aHR 95% UCL ) of pretransplant ME level with patient and graft survival over 5 years after transplant were quantified by multivariate Cox regression including adjustment for recipient, donor, and transplant factors, as well as propensity adjustment for opioid use. Overall, 9.3% of recipients filled opioids on the waiting list. Compared with no use, level 3 (aHR 1.06 1.28 1.55 ) and 4 (aHR 1.16 1.52 1.98 ) opioid use during listing were associated with increased mortality over 5 years after transplant. These associations were driven by risk after the first transplant anniversary, such that mortality >1-5 years increased in a graded manner with higher use on the waiting list (level 2, aHR, 1.00 1.27 1.62 ; level 3, aHR, 1.08 1.38 1.77 ; level 4, aHR, 1.49 2.01 2.72 ). Similar patterns occurred for graft failure. Of recipients with the highest level of opioids on the waiting list, 65% had level 3 or 4 use in the first year after transplant, including 55% with use at these levels from day 90-365 after transplant. Opioid use in the first year after transplant also bore graded associations with subsequent death and graft loss >1-5 years after transplant. Opioid use history may be relevant in assessing and providing care to LT candidates. Liver Transplantation 23 305-314 2017 AASLD., (© 2016 by the American Association for the Study of Liver Diseases.)

While the costs to Medicare of solid organ transplants are varied and considerable, the total Medicare expenditure of $4.4 billion for solid organ transplant recipients in 2014 remained less than 1% of all Medicare expenditures. For patients covered by Medicare, the ratio of pre- to posttransplant cost of care varied widely by organ and within some organ categories by patient characteristics. This chapter reports pretransplant costs for all solid organ candidates covered by Medicare to allow investigators to further explore the relative cost of transplant compared with alternative management., (.)

While the costs to Medicare of solid organ transplants are varied and considerable, the total Medicare expenditure of $4.2 billion for solid organ transplant recipients in 2013 remains less than 1% of all Medicare expenditures. Kidney transplant remains one of the most cost-effective surgical interventions in medicine and exhibits a rare feature in that it is generally known to be cost-saving in the long term. For patients covered by Medicare, lung transplant is one of the more costly solid organ transplants performed. This chapter reports pretransplant costs for lung candidates to allow investigators to further explore the relative cost of lung transplant compared with alternative management., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: The outcomes and optimal management of cirrhotic patients who develop cryptococcosis before transplantation are not fully known., Methods: We conducted a multicenter study involving consecutive patients with cirrhosis and cryptococcosis between January 2000 and March 2014. Data collected were generated as standard of care., Results: In all, 112 patients were followed until death or up to 9 years. Disseminated disease and fungemia were present in 76.8% (86/112) and 90-day mortality was 57.1% (64/112). Of the 39 patients listed for transplant, 20.5% (8) underwent liver transplantation, including 2 with active but unrecognized disease before transplantation. Median duration of pretransplant antifungal therapy and posttransplant therapy was 43 days (interquartile range, 8-130 days) and 272 days (interquartile range, 180-630 days), respectively. Transplantation was associated with lower mortality (P = 0.002). None of the transplant recipients developed disease progression during the median follow-up of 3.5 years with a survival rate of 87.5%., Conclusions: Cryptococcosis in patients with cirrhosis has grave prognosis. Our findings suggest that transplantation after recent cryptococcal disease may not be a categorical exclusion and may be cautiously undertaken in liver transplant candidates who are otherwise deemed clinically stable.

There is limited data pertaining to the risk of End Stage Renal Disease (ESRD) after living kidney donation. The Organ Procurement and Transplantation Network and the Center for Medicare and Medicaid Services databases were used to identify living kidney donors (LKDs) who subsequently developed ESRD and to calculate LKD ESRD rates. We found 126 cases of ESRD among 56 458 LKDs (0.22%) who donated during October 1, 1987-March 31, 2003. The overall LKD ESRD rate was 0.134 per 1000 years at risk, with an average duration of follow-up of 9.8 years. ESRD rates for LKDs overall and for Black, White, male and female donors compared favorably to the ESRD incidence in the general population. The LKD ESRD rate was nearly five times higher for Blacks than for Whites and two times higher for males than females. However, these ethnic and gender-related differences were similar to those previously reported for ESRD in the general population. Our findings do not show an increase in the risk of ESRD for LKDs and support the current practice of living kidney donation. Further research is needed to determine if improved donor screening or follow-up will reduce the risk of postdonation ESRD., (©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The frequency of combined liver and kidney transplants (CLKT) persists despite the pronounced scarcity of organs. In this review, we sought to ascertain any factors that would reduce the use of these limited commodities. Seventy-five adult CLKT were performed over a 23-yr period at our center, 29 (39%) of which occurred during the Model for End-stage Liver Disease (MELD) era. Overall, patient survival rates were 82%, 73%, and 62% at one, three, and five yr, respectively. There was no difference in patient survival based either on pre-transplant hemodialysis status or by glomerular filtration rate (GFR) at the time of transplant. Patients undergoing a second CLKT or a liver retransplantation at the time of CLKT had a survival rate of 30% at three months. In the MELD era, patient survival was unchanged (p = NS) despite an older recipient population (p = 0.0029) and a greater number of hepatitis C patients (p = 0.0428). In summary, patients requiring liver retransplantation with concomitant renal failure should be denied CLKT. Renal allografts may also be spared by implementing strict criteria for renal organ allocation (GFR < 30 mL/min at the time of evaluation) and considering the elimination of preemptive kidney transplantation in CLKT., (© 2009 John Wiley & Sons A/S.)

Coincident with an increasing national interest in equitable health care, a number of studies have described disparities in access to solid organ transplantation for minority patients. In contrast, relatively little is known about differences in posttransplant outcomes between patients of specific racial and ethnic populations. In this paper, we review trends in access to solid organ transplantation and posttransplant outcomes by organ type, race and ethnicity. In addition, we present an analysis of categories of factors that contribute to the racial/ethnic variation seen in kidney transplant outcomes. Disparities in minority access to transplantation among wait-listed candidates are improving, but persist for those awaiting kidney, simultaneous kidney and pancreas and intestine transplantation. In general, graft and patient survival among recipients of solid organ transplants is highest for Asians and Hispanic/Latinos, intermediate for whites and lowest for African Americans. Although much of the difference in outcomes between racial/ethnic groups can be accounted for by adjusting for patient characteristics, important observed differences remain. Age and duration of pretransplant dialysis exposure emerge as the most important determinants of survival in an investigation of the relative impact of center-related versus patient-related variables on kidney graft outcomes.

Background: The immunosuppressive medications that have contributed greatly to the success of liver transplantation are also associated with posttransplant renal dysfunction. We reviewed measured glomerular filtration rate (GFR) data from patients who underwent transplantation more than 10 years ago to assess whether results from specific time points can predict renal failure., Methods: The GFR data were obtained at initial evaluation (IE), at month 3, and at years 1, 2, 5, 10, and 15. Two groupings were compared, one based on GFR at IE and the other at month 3. Patients were further stratified into three GFR (mL/min/1.73 m2) groups: G1, GFR more than 80; G2, GFR 60 to 80; and G3, GFR less than 60., Results: A total of 592 liver transplant recipients met the inclusion criteria; 114 had paired GFR data from IE to year 15. Analysis of paired and censored data based on IE GFR showed that 62.2% of G3 patients developed renal failure by year 5; another 6.7% did so by year 10 (P=0.027). The month 3 GFR data showed that 56.3% of G3 patients developed renal failure by year 5; another 15.6% did so by year 10. Surprisingly, 37.0% of G2 patients experienced renal failure by year 5; another 11.1% did so by year 10 (P=0.0024)., Conclusions: The month 3 data indicate a slow but steady decline in GFR over years. The lower the initial GFR is after transplant, the sooner renal failure develops. Patients with GFR less than 60 mL/min per 1.73 m2 at month 3 have a higher risk of renal failure; however, those who avoid renal failure seem to maintain renal function long term.

Islet transplantation, an innovative treatment strategy for type 1 diabetes mellitus, is a relatively safe procedure, with less morbidity than pancreas transplantation. Vascular injuries have not been reported to date. We report a percutaneous transhepatic intraportal islet transplant infusion that was followed by bleeding from a false aneurysm of an intrahepatic branch of the hepatic artery. The bleeding was controlled by selective embolization. Despite the complication and its treatment, the patient gained insulin independence, which was sustained for 285 days. She is currently on a small dose of insulin with good glycemic control.

Arterial problems remain a formidable challenge in liver transplantation. In many situations, an aortohepatic conduit can provide a solution. No long-term results (over 5 years) have been reported. This study was designed to assess the impact of aortohepatic conduits on graft survival after liver transplantation and the safety of aortohepatic conduits and to establish the long-term results (up to 20 years) of aortohepatic conduits. Data from 2346 adult liver transplants were prospectively collected into the computerized database and analyzed. In the majority of cases, arterial conduits were constructed from the donor iliac artery obtained at the liver retrieval. Aortohepatic conduits were required in 149 (6.4%) first transplants. The long-term graft survival after liver transplantation using aortohepatic conduits was excellent and comparable to that of the control group. The graft survival was 59% with the conduit versus 67% without the conduit at 5 years of follow-up, 50% versus 52% at 10 years, and 33% versus 35% at 15 years. With up to 20 years of follow-up, there was no statistically significant difference in graft survival, patient survival, hepatic artery complications, or biliary complications. For the same time period, there was no statistically significant difference in graft survival or patient survival for the retransplants with and without aortohepatic conduits. In conclusion, in experienced hands, aortohepatic conduits can be used safely for liver transplantation with no negative impact on long-term graft survival, patient survival, hepatic artery complications, or biliary complications. Excellent long-term results can be obtained., ((c) 2008 AASLD.)

Hepatic allograft rejection still remains an important problem following liver transplantation. Early acute rejection, occurring within three months of transplant, is a common event and usually of lesser significance with respect to prognosis than other non-immune-related post-transplant morbidities. However, little is known about late acute rejection (LAR) including factors affecting its occurrence and long-term outcome. In this study, we analyzed LAR including the incidence, clinical risk factors, patient survival, and graft survival. LAR was defined as acute cellular rejection later than six months after liver transplant. Adult patients who had a minimum of 24 months of graft survival were included in this study. A total of 1604 case records of consecutive adult patients (over age 18 yr) who underwent liver transplant between 1985 and 2003 were reviewed. Of the 1604 patients, 305 (19.0%) developed LAR. Patients with primary diagnoses of autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis had higher incidences of LAR, while patients with metabolic disease and retransplant had lower incidence of LAR (p = 0.0024). The LAR group had more female and younger recipients than the no LAR group (p = 0.0026, p = 0.0131, respectively). Patient survival as well as graft survival were significantly lower in the LAR group (p = 0.0083, p = 0.0075, respectively). PTLD was the only significant independent predictor of late rejection. The careful management and treatment of PTLD, especially immunosuppressive management, is important to prevent LAR, which is related to poorer patient survival.

Purpose: To expand our knowledge on liver transplantation for cirrhosis associated with cystic fibrosis in adults., Methods: Five patients who underwent a liver transplantation due to cystic fibrosis were reviewed. The outcome of the patients in terms of age, immunosuppression regimen, patient and graft survival, and pre- and post-transplant complications were investigated., Results: Five adult liver transplant patients had cystic fibrosis (0.2%). These included 4 men and 1 woman with a mean age of 31 +/- 10, ranging from 22 to 52 years old at the time of transplantation. All patients had lung problems. Four patients had exocrine and two had endocrine pancreatic insufficiency. Two are currently alive with a follow-up of 5.8 years and 4 months after transplantation, respectively. There were three deaths from pulmonary embolism at 4.5 years, myocardial infarction with cyclosporine nephrotoxicity at 10.7 years, and lymphoproliferative disorder at 5 months after transplantation. No deaths occurred from lung infection. Only one patient had postoperative pulmonary infectious complications, which were successfully treated with antibiotics and did not result in mortality., Conclusion: Adult liver transplantation for end-stage liver disease associated with cystic fibrosis offers encouraging results with a rapid general improvement after surgery and it is now considered to be a safe and acceptable treatment for this disease population.

Hepatorenal syndrome (HRS) is a well-recognized complication of end-stage liver disease. Once thought to be a reversible condition with liver transplantation (LT) alone, HRS may directly contribute to the requirement for long-term dialysis posttransplant. As a result, discussion has now focused on whether or when a kidney allograft should be considered for these patients. Using the International Ascites Club guidelines with a pretransplant serum creatinine (SCr) >2.0 mg/dL to define HRS, 130 patients undergoing LT over a 10-yr period were identified, for an overall incidence of 9%. Patient survival rates at 1, 3, and 5 yr were 74%, and 68%, and 62%, respectively. Survival was significantly worse when compared to non-HRS patients undergoing LT over the same study period (P = 0.0001). For patients presenting with type 2 HRS, 7 patients (6%) developed irreversible kidney failure posttransplant compared to 0.34% in the non-HRS population (P < 0.0001). Five of these patients died within 1 yr with a median survival time of 139 days. Combined liver and kidney transplantation (CLKT) for patients with HRS is not recommended. However, an improvement in outcome can be accomplished by addressing those patients who require dialysis greater than 60 days posttransplant. We propose a role for kidney after liver transplantation (KALT) in select HRS patients.

Initial graft function following liver transplantation is a major determinant of postoperative survival and morbidity. Primary graft nonfunction (PNF) is uncommon; however, it is one of the most serious and life-threatening conditions in the immediate postoperative period. The risk factors associated with PNF and short-term outcome have been previously reported, but there are no reports of long-term follow-up after retransplant for PNF. At our institution, 52 liver transplants had PNF (2.22%) among 2,341 orthotopic liver transplants in 2,130 patients from 1984 to 2003. PNF occurred more often in the retransplant setting. Female donors, donor age, donor days in the intensive care unit, cold ischemia time, and operating room time were significant factors for PNF. Patient as well as graft survival of retransplant for PNF was not different compared to retransplant for other causes. However, PNF for a second or third transplant did not demonstrate long-term survival, and hospital mortality was 57%. In conclusion, retransplant for PNF in the initial transplant can achieve relatively good long-term survival; however, if another transplant is needed in the setting of a second PNF, the third retransplant should probably not be done due to poor expected outcome., ((c) 2007 AASLD.)

Background: Radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) is an optional treatment for patients awaiting liver transplantation (LTX). The study evaluates the efficacy of RFA in the explanted liver and its effect on patient outcome., Material and Method: Forty-seven patients underwent RFA and were listed for transplant between January 1998 and May 2003. The patients were divided into two groups: transplanted and non-transplanted. Both groups were evaluated in terms of tumor characteristics, recurrence, mortality rate, and time on the waiting list. The ablation sites in the explanted livers were examined for percentage of necrosis by Hematoxylin & Eosin (H&E) stain and by TUNEL stain., Results: Transplantation was carried out in 35 patients (74.5%). Ten patients (21.3%) died before transplant or were removed from the wait list, while two patients (4.2%) are still listed. Mortality and tumor-related mortality were significantly higher in the non-transplanted group. The time spent on the waiting list was longer in the non-transplanted patients (350 vs. 186 d average, p = 0.0345). Thirty-eight ablation sites were examined in the explanted livers. The percentage of tumor necrosis by TUNEL staining was 19.6% higher than that reported by H&E staining. After TUNEL staining, 28 sites (73.7%) had more than 90% necrosis, eight sites (21.0%) had 50-90%, and two sites (5.3%) had less than 50% necrosis., Conclusions: RFA and LTX can be used successfully in HCC patients, and in most cases, tumor necrosis can be achieved with ultrasound-guided RFA. H&E stain tends to under-represent the amount of tumor necrosis on the ablation sites. Survival of RFA patients after LTX is excellent.

Background: Polycystic liver disease (PLD) is a rare disorder frequently associated with polycystic kidney disease (PKD). Transplantation is a treatment option for these patients. Because of preservation of hepatic function in these patients, liver transplantation is not routinely utilized. We report a large series of PLD patients and their outcomes following liver and kidney transplantation., Methods: Fourteen patients underwent orthotopic liver transplantation (OLTx) for PLD between 1987 and 2003. Twelve patients had PKD combined with PLD. Nine patients received only liver transplantation. Five patients had combined liver and kidney transplantation. Thirteen patients (93%) survived for at least one year following liver transplantation. Two out of eight patients who received solitary liver transplantation later required kidney transplantation., Results: Pretransplant glomerular filtration rate (GFR) in patients with PKD was 75.8+/-25.4 ml/min/1.73 m. One year later, GFR was 37.2+/-8.3 ml/min/1.73 m. Kaplan-Meier analysis showed that one- and two-year graft survival for combined liver and kidney transplantation was 80% (n=5), whereas graft survival for solitary liver transplantation was 100% (n=9). Mean survival of patients who had combined liver and kidney transplantation was 46.7+/-54.2 months (n=5), whereas the mean survival for solitary liver transplant patients was 80.4+/-68.6 months (n=9) (P=0.36)., Conclusion: Transplantation is an excellent option for PLD with dramatic improvement in quality of life and acceptable morbidity. For combined liver and kidney transplantation one- and two-year patient survival rates were similar to combined transplantation for other indications. For patients with acceptable renal function at time of transplantation, solitary liver transplantation has an excellent outcome.

Survival after liver retransplantation (RLTX) is worse than after primary liver transplantation (LTX). We studied retrospectively the 2-year outcome in 44 patients who received RLTX more than 30 days after the primary transplant and in 669 after LTX performed between December 1993 and October 1999, focusing on the relation between the model for end-stage liver disease (MELD) score immediately pretransplant and post-transplant survival. A 2-year survival for RLTX was inferior to LTX (65.9% vs. 82.9%, P < or = 0.01). This difference was greatest with MELD scores < 25; survival within 2 years remained 11.3-18.2% less for RLTX than for LTX (6 months, P = 0.002; 12 months, P = 0.029, 24 months, P = 0.123). Mortality was mainly related to early vascular complications and sepsis. Two-year survival after RLTX was 81.8% if RLTX occurred < 2 years after LTX and 50% if the interval between LTX and RLTX was > 2 years (P < 0.05). MELD scores were similar in 2-year survivors and nonsurvivors after late RLTX (P = 0.82). Late RLTX is marked by poor survival regardless of the pretransplant MELD score. The MELD-based allocation system may not benefit patients who undergo retransplantation.

Hepatic artery stenosis after liver transplantation may affect liver function and result in hepatic artery thrombosis. Surgical reconstruction has been the first choice for treatment. Interventional radiologic technique can be used, but there is no report on long-term outcome. The aim of this paper is to assess current outcome and complications of hepatic artery stenting. Twenty-six adult patients were stented for hepatic artery stenosis between 1998 and 2003. Nine patients had previous surgical reconstruction for hepatic artery stenosis. Seventeen patients suffered newly developed hepatic artery stenosis. Three patients were retransplanted. After stenting, the patients were followed by Doppler ultrasound at day 1, 1 month, and 6 months. Angiography was scheduled in 6 months. Four patients died within 2 months. The other 22 patients were followed for mean 31 +/- 14 months (8-71 months). One of 22 patients died from renal failure 2 years later. Twelve patients' hepatic arteries looked normal after stenting. Restenosis was seen in 8 patients (36%). Other complications were artery thrombosis (n = 1) and long segment stricture (n = 1). In 2 patients (25%) restenosis resulted in thrombosis. Six of the 8 patients who developed recurrent stenosis were successfully treated interventionally: restent (n = 5) and balloon dilation (n = 3). However, 3 patients (38%) restenosed. Kaplan-Meier complication-free survival was 54% at 1 year after stenting. In conclusion, hepatic artery stenting is a viable treatment for hepatic artery stenosis with reasonable results. Stenting is useful as adjuvant treatment after surgical revision., (Copyright 2006 AASLD)

Methods: We reviewed our prospectively maintained database of 2005 liver transplantations. Therapy was either started de novo or converted from calcineurin inhibitors (CNIs) to sirolimus as the main immunosuppressive agent for nephrotoxicity or rejection. Glomerular filtration rate (GFR) was determined with iodine 125-labeled sodium isthalamate (Glofil-125), and serum creatinine concentration was obtained before and 3 months after transplantation, and yearly in both groups. Sirolimus levels were 10 to 15 ng/mL in patients at less than 3 months after transplantations and 5 to 10 ng/mL in the remaining patients. All patients received mycophenolate mofetil as maintenance therapy., Results: Data for 29 patients in the de novo group and 35 in the conversion group were reviewed. Patients in the de novo group demonstrated an acute cellular rejection rate of 17.2%, 40% of which were steroid resistant. In this group, 48.2% discontinuation of sirolimus was necessary because of adverse effects. Patients in the conversion group demonstrated an acute cellular rejection rate of 2.8% and a 34.3% rate of sirolimus discontinuation. Seventeen (56.7%) patients at 1 year and 8 (44.4%) patients at 2 years demonstrated continued improvement in GFR. In the conversion group, case-control analysis did not demonstrate a significant difference in GFR and serum creatinine concentration (P > .05) at 1 and 2 years after conversion. At the time of review, no patients in the conversion group required hemodialysis., Conclusions: Conversion to sirolimus therapy is an effective strategy in improving renal function in patients with CNI-induced nephrotoxicity and can be done without increased rejection. Most of our patients (65.7%) tolerated sirolimus conversion. Of these, 56.7% and 44.4% demonstrated continued increase in GFR with the CNI-free regimen at 1 and 2 years, respectively. Long-term, large-population, prospective, randomized, controlled studies should further validate these results.

The COACH syndrome is a very rare disorder with cerebellar vermis hypoplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis. Nineteen cases with COACH diagnosis have been reported. Neurologic abnormalities are the first symptoms in most cases. Complications of the hepatopathy [portal hypertension, esophageal varices, and gastrointestinal (GI) bleeding] contribute extensively to the morbidity and lethality in the course of the disease. We describe a 28-yr-old female with COACH syndrome resulting in chronic renal and hepatic insufficiency. The patient was found to have significant mental retardation, truncal ataxia, motor abnormality and occulomotor abnormality. She began to develop GI bleeding and encephalopathy because of biopsy-confirmed cirrhosis. We performed combined liver and kidney transplant after challenging discussion. Her postoperative course was uneventful, and she was discharged on the ninth postoperative day (POD). She has not had any problems at 1, 3 and 5-yr follow-up with excellent liver and renal function. This is the first description of successful combined liver and kidney transplant with long-term follow-up. The decision for transplant is challenging because COACH syndrome is rare with only descriptive characterization and patients have non-progressive ataxia and mental retardation. However, our case shows that liver and kidney transplant can be medically successful, and the individuals achieve long-term success if they have a stable neurological condition and an excellent support system.

The goals of this study were to assess waitlist morbidity in terms of the frequency of health care services utilized by patients while on the liver transplant (LTX) waiting list and to determine whether that utilization can be predicted by the Model for End-Stage Liver Disease (MELD). Sixty-three noncomatose subjects were followed from waitlist placement until death, change in status, LTX, or study discontinuance. Health care events included doctor/clinic visits, labs, outpatient/inpatient tests and procedures, and hospital/intensive care unit days. Listing MELD scores and LTX MELD scores were examined against the number of health care event occurrences within 60 days of listing and 60 days of LTX, respectively, as were changes in MELD scores between listing and LTX and differences in the number of occurrences between the two time points. The only significant correlations noted were between LTX MELD scores and number of hospital days near LTX (r = .360, P = .046) and between LTX MELD scores and the sum total number of occurrences near LTX (r = .370, P = .044). These results suggest that MELD scores do not appear to predict morbidity in terms of health care utilization in patients awaiting LTX. Developing a system capable of predicting waitlist morbidity may lead to the implementation of medical interventions aimed at circumventing foreseeable complications and/or crises in patients awaiting LTX.

Background/aims: Biliary anastomotic complications remain a major cause of morbidity in liver transplant recipients. The objective of this retrospective study is to reassess the use of anastomotic stents for biliary reconstruction while focusing on an end-to-end choledochocholedochostomy (EECC) in orthotopic liver transplantation (OLT)., Methodology: EECC for the biliary reconstruction in OLT was performed in 115 patients. Sixty-three had their bile duct reconstructed over a T-tube stent (S group) while the remaining 52 patients underwent the same procedure without the stent (non-S group). The two groups were compared in terms of biliary complications and the conversion rate to a hepaticojejunostomy (HJS)., Results: Twenty-three biliary complications were observed in the OLT patients. In the S group, the incidence of a biliary leak was 12.7%, 8 of 63 patients in which 5 patients showed a bile leak when T tubes were removed. The rate of biliary stricture in the S group was 25.4%, or 16 patients. This stricture rate was not significantly different from the 13.5% rate observed in the non-S group (p=0.086). In the non-S group, 7 patients showed a biliary stricture. Four of 7 patients also developed a bile leak identified to be an anastomotic leak, which consequently resulted in HJS. A total of 6 patients, 5.2% of all OLT patients, underwent a subsequent revision of their primary anastomoses. The incidence of conversion from EECC to HJS in the non-S group, 57.1% was significantly higher than that in the S group, 12.5% (p=0.046)., Conclusions: EECC (i.e. with or without a T-tube stent) is both a safe and effective technique for biliary reconstruction in OLT. However, the conversion rate from EECC to HJS in the non-S group was significantly higher than that in the S group. An indwelling T-tube stent is therefore considered to be useful for both achieving the lowest possible rate of severe anastomotic stricture and to prevent any subsequent intervention.

This case report describes a patient who underwent orthotopic liver transplantation and developed extensive hyperacute venous and arterial intravascular thromboses and thromboemboli intraoperatively. The patient was receiving antifibrinolytic therapy with aprotinin. The safety of routine aprotinin therapy in liver transplantation is examined. The value of the thrombelastograph (TEG) as a qualitative assessment of the coagulation system is emphasized.

As the Baylor Regional Transplant Institute celebrates its 20-year anniversary and the transplant of its 2,500th liver, the program has continued to grow, reaching its highest yearly volume to date. Twenty years gives an excellent opportunity to see how the facets of our program have adjusted in response to changes in both society and our own field of transplantation. Our recipient and donor demographics have changed significantly, but despite older recipients, older and more marginal donors and the issues of disease recurrence, we have consistently improved survival of both the patient and graft, reduced rejection rates and minimized hospital and ICU stays. These survival improvements have been even more pronounced in patients transplanted for HCC. Because of constantly changing risk and complication patterns, we have continually analyzed and adapted our processes and protocols, adjusting them in response to patient outcomes and the best current scientific evidence when needed. The research at Baylor has always had a practical, clinical dimension, but with development of our "Genes of Health" program at the Baylor Institute of Immunology Research, we hope to expand more basic science transplant research and most importantly take the lead in translational research.

Malnutrition is common in severe liver disease. Assessment of malnutrition usually requires a subjective global assessment of the patient with a few additional tests that often include handgrip strength and arm-muscle circumference. The severity of liver disease correlates well with the severity of malnutrition, which has prognostic value. Malnutrition is multifactorial, is difficult to correct, and occurs in liver disease independently of the etiology of hepatic injury. Patients who have severe protein-calorie malnutrition require diets with high calorie and protein intake, even in the presence of hepatic encephalopathy. Some forms of complementary and alternative medicine are frequently used in patients with advanced liver disease, but supporting scientific data is needed. Obesity is detrimental to patients with advanced liver disease and is of greater concern in liver transplant candidates because it increases transplant-related morbidity. Data detailing the effects of aggressive nutritional support before transplantation are scarce, and more studies are needed.

In summary, it should be noted that patients with underlying chronic liver disease such as viral hepatitis have many alternatives for therapy, including resection and transplantation. It is imperative that these patients receive early referral to a center with experience in performing liver resections and the ability to perform hepatic transplantation.

Background: National sharing of cadaveric renal allografts for perfectly matched kidneys (0 antigen mismatch) has improved outcome in the recipients of these kidneys despite increasing cold storage times. However, there may be limits to outcome improvement of matched kidneys based on age and cold storage time., Materials and Methods: To determine if national sharing of kidneys based on matching improves outcome regardless of donor age and cold storage time, we evaluated the United Network for Organ Sharing (UNOS) Scientific Registry for all recipients of cadaveric kidney transplants between January 1, 1990 and July 31, 1998. We divided the recipients into four groups based on donor age and cold storage time. Group 1 comprised young donors (donor age <55 years) with average (<24 h) cold storage time; group 2, young donors with long (>/=24 h) cold storage time; group 3, older donors (donor age >/=55 years) with average cold storage time; and group 4, older donors with long cold storage time., Results: A total of 64,046 recipients were evaluated: 35,061 (55%) in group 1, 21,264 (33%) in group 2, 4308 (7%) in group 3, and 3414 (5%) in group 4. Early graft performance progressively decreased from group 1 to group 4. Delayed graft function (DGF: dialysis requirement in the first 7 days posttransplant) was 18, 29, 33, and 42% (P < 0.0001); serum creatinine at 3 years (in mg/dl) was 1.70 +/- 0.8, 1.73 +/- 0.9, 2. 31 +/- 1.0, and 2.42 +/- 1.1 (P < 0.0001); 1-year graft survival was 87, 84, 79, and 77% (P < 0.0001); and 3-year graft survival was 77, 74, 63, and 62% (P < 0.0001, for groups 1 and 2 vs groups 3 and 4, respectively). The trends in DGF persisted through the groups in 0 antigen mismatched kidneys., Conclusions: Early function is adversely affected by prolonged cold storage, despite matching, in recipients of younger and older donor kidneys. Long-term function does not appear to be affected by prolonged cold storage. Recipients of kidneys from donors >/=55 years of age have significantly worse short- and long-term outcome and may not benefit from national sharing., (Copyright 2000 Academic Press.)

Objective: To evaluate the impact of surgical complications on length of stay and hospital charges after liver transplantation., Design: A retrospective economic evaluation of the outcomes during initial hospitalization after liver transplantation., Setting: University hospital treating referred patients., Patients: The study population was 109 patients undergoing 111 liver transplantations during fiscal year 1993., Main Outcome Measures: Hospital charges and length of stay during the initial hospitalization after liver transplantation. Multivariate regression methods were used to analyze the impact of surgical complications on costs., Results: Of the 111 transplantations, 30 (27%) had a surgical complication that required a return to the operating room during the initial hospitalization. The effect of a surgical complication was to increase the mean hospital charges (excluding physician charges) from $150,092 to $347,728 (difference of mean, $197,636; confidence interval of difference, $114,153 to $319,326). The median length of stay was 16 days for patients without complications and 45 days for those with complications. Univariate and multivariate models suggested that surgical complications had the greatest effect on length of stay and hospital charges among the factors studied. Complications tended to occur more frequently among patients with United Network for Organ Sharing (UNOS) status 1 (42% vs 22%), but this did not reach statistical significance (P = .09)., Conclusions: Surgical complications after liver transplantation have a marked impact on the cost of the procedure. The magnitude of this effect is greater than that of UNOS status, presence of rejection, or other demographic or clinical factors studied. Complications tend to occur in the most ill patients. Identifying strategies to reduce the risk of complications, particularly in patients with UNOS status 1, likely can reduce the cost of transplantation.

The relationship between liver regeneration and the induction of the immune response is uncertain. We hypothesize that the altered environment of the regenerating liver allograft increases the immune response to the allograft. In DA (RT1a) to LEW (RT1I) rats, hepatectomized, small-for-size and whole, normal-for-size liver transplants were performed. Naive and 70% hepatectomized LEW served as controls. Animals were assessed for survival, mass restoration, and host alloresponses. Although 30% partial allografts regenerated well to achieve a volume nearly equal to that of recipient's native liver in 7 days, survival was significantly shorter than that of the recipients of whole grafts (8.8 +/- 0.4 vs 10.3 +/- 1.2 days, n = 6, P < 0.02). When compared on Day 4 after transplantation, histologic examination revealed a more vigorous cellular infiltration in the sinusoidal area in the partial liver transplant group. Phenotypic analysis of thymocytes showed a predominance of more mature phenotypes in the partial group, including more prominent decrease in the frequency of CD4, CD8-double-positive cells and increase in that of alpha beta TCRhigh cells. Proliferative activity of thymocytes in response to Con A was higher in the partial group than in the whole group. MLR of splenocytes against donor-type antigens was higher in the partial group, whereas reactivity against third party was the same as in other groups. These data suggest that host cellular responses to the allograft are enhanced in the regenerating, small-for-size liver graft. These findings have implications in the clinical management of liver recipients with damaged or small for size livers.

An end-to-end choledochocholedochostomy (CD) over a T tube or a Roux-en-Y choledochojejunostomy (CDJ) have been the standard method of biliary reconstruction following orthotopic liver transplantation (OLTx). The objective of this study was to assess whether or not use of the T tube leads to increased biliary tract complications. Biliary tract complications were categorized as bile leak, stenosis, or obstruction that required therapeutic intervention. OLTx was performed in 161 patients over an 18-month period. Fifty-one patients were excluded from the study leaving a total of 110 patients for evaluation. Fifty-nine had their bile duct reconstructed over a T tube (CD T tube, group I) while the remaining 51 patients underwent bile duct reconstruction without a T tube (CD, group II). No difference was noted between groups I and II in their survival rate, rate of conversion to Roux-en-Y CDJ, or biliary complication rates. Our results indicate that CD (i.e., without a T tube) is both a safe and effective technique to reconstruct the biliary tract following hepatic transplantation. Routine use of a T tube with a CD anastomosis is unnecessary in most liver transplant patients. In addition, the omission of a T tube has reduced the number of radiological procedures performed at our center.