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Ruiz R, Jennings LW, Kim P, Tomiyama K, Chinnakotla S, Fischbach BV, Goldstein RM, Levy MF, McKenna GJ, Melton LB, Onaca N, Randall HB, Sanchez EQ, Susskind BM, Klintmalm GB. Indications for combined liver and kidney transplantation: propositions after a 23-yr experience. Clin Transplant 2010: 24: 807-811. © 2009 John Wiley & Sons A/S. 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. [ABSTRACT FROM AUTHOR]

Angiotensin II type-1 receptor (AT 1 R) and endothelin-1 type A receptor (ET A R) autoantibodies, in addition to allograft injury, can bind native endothelial cells and cause vascular vasoconstriction and fibrosis progression in nontransplanted organs. Therefore, we investigated long-term native renal function in liver transplant (LT) recipients with and without anti-AT 1 R-Abs and/or anti-ET A R-Abs present in serum. Primary LT recipients at our single center from January 2000 to April 2009 had their prospectively collected pre-LT (1269 patients) and year 1 post-LT (795 patients) serum tested retrospectively for anti-AT 1 R-Abs and/or anti-ET A R-Abs. Anti-AT 1 R-Abs and anti-ET A R-Abs testing was accomplished with a standardized solid phase assay in which >10 U was considered positive. Pretransplant anti-AT 1 R-Abs and/or anti-ET A R-Abs did not change the median delta creatinine from pretransplant to 1 year post-transplant. In multivariable analysis controlling for diabetes (DM) and calcineurin inhibitor (CNI) use, anti-AT 1 R-Abs and/or anti-ET A R-Abs at 1-year remained statistically significantly associated with a decline in GFR (measured by Modification of Diet in Renal Disease-6) from years 1-5 post-LT (P =.04). In diabetic patients the association with a decline in renal function was more pronounced with (-9.29 mL/min) vs without (-2.28 mL/min) anti-AT 1 R-Abs and/or anti-ET A R-Abs at year 1, respectively (P =.004). At 1-year post-LT, the autoantibodies anti-AT 1 R-Abs and/or anti-ET A R-Abs are associated in multivariable analysis with an increased risk of native renal function decline especially in diabetic patients. [ABSTRACT FROM AUTHOR]

Liver transplantation is the optimal treatment for patients with hepatocellular carcinoma ( HCC) and cirrhosis. This study was conducted to determine the impact of pre-transplant locoregional therapy ( LRT) on HCC and our institution's experience with expansion to United Network of Organ Sharing Region 4 T3 ( R4 T3) criteria. Two hundred and twenty-five patients with HCC (176 meeting Milan and 49 meeting R4 T3 criteria) underwent liver transplantation from 2002 to 2008. Compared with the Milan criteria, HCCs in R4 T3 criteria displayed less favorable biological features such as higher median alpha-fetoprotein level (21.9 vs. 8.5 ng/mL, p = 0.01), larger tumor size, larger tumor number, and higher incidence of microvascular invasion (22% vs. 5%, p = 0.002). As a result, patients meeting Milan criteria had better five-yr survival (79% vs. 69%, p = 0.03) and a trend toward lower HCC recurrence rates (5% vs. 13%, p = 0.05). Pre-transplant LRT did not affect post-transplant outcomes in patients meeting Milan criteria but did result in lower three-yr HCC recurrence (7% vs. 75%, p < 0.001) and better three-yr survival (p = 0.02) in patients meeting R4 T3 criteria. Tumor biology and pre-transplant LRT are important factors that determine the post-transplant outcomes in patients with HCC who meet R4 T3 criteria. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Context.—Establishing adequate interobserver agreement is crucial not only for standardization of patient care but also to ensure validity of findings in multi-institutional trials. Objective.—To evaluate interobserver agreement in assessing chronic hepatitis C (HCV) and acute cellular rejection (ACR) among 17 hepatopathologists involved in the ''Hepatitis C 3'' trial. Design.—The trial is a randomized multicenter (17 institutions) study involving 312 patients undergoing transplantation for HCV. Patients are randomized to 3 treatment arms. For final data analysis, all biopsy specimens are reviewed by a central pathologist (G.J.N.). Recurrence of HCV is evaluated according to the Batts and Ludwig schema. The 1997 Banff schema is used to evaluate ACR. To assess interobserver agreement, hematoxylin-eosin-stained sections from 11 liver biopsy specimens (6 HCV and 5 ACR) were sent by the central pathologist to 16 local pathologists from 13 institutions. Statistical analysis was performed on raw ACR/HCV data as well as data grouped according to clinically significant primary endpoint cutoffs. Results.—Statistically significant agreement was found among all participating pathologists (P < .001). On κ analysis, the degree of agreement was rated ''moderate'' for HCV grade and stage and ACR global grading (κ = 0.30, 0.33, and 0.37, respectively). Interobserver agreement was weaker for rejection activity index scoring of ACR (κ = 0.15). A stronger degree of agreement was found when scores were grouped based on endpoint cutoffs (κ = 0.76 ''almost perfect'' for HCV and 0.62 ''substantial'' for ACR). Conclusions.—An overall statistically significant interobserver agreement was found among 17 pathologists using the 1997 Banff schema and the Batts and Ludwig schema. [ABSTRACT FROM AUTHOR]