Defining Benchmarks in Liver Transplantation: A Multicenter Outcome Analysis Determining Best Achievable Results.

: This multicentric study of 17 high-volume centers presents 12 benchmark values for liver transplantation. Those values, mostly targeting markers of morbidity, were gathered from 2024 "low risk" cases, and may serve as reference to assess outcome of single or any groups of patients. OBJECTIVE: To propose benchmark outcome values in liver transplantation, serving as reference for assessing individual patients or any other patient groups. BACKGROUND: Best achievable results in liver transplantation, that is, benchmarks, are unknown. Consequently, outcome comparisons within or across centers over time remain speculative. METHODS: Out of 7492 liver transplantation performed in 17 international centers from 3 continents, we identified 2024 low risk adult cases with a laboratory model for end-stage liver disease score ≤20 points, a balance of risk score ≤9, and receiving a primary graft by donation after brain death. We chose clinically relevant endpoints covering intra- and postoperative course, with a focus on complications graded by severity including the complication comprehensive index (CCI). Respective benchmarks were derived from the median value in each center, and the 75 percentile was considered the benchmark cutoff. RESULTS: Benchmark cases represented 8% to 49% of cases per center. One-year patient-survival was 91.6% with 3.5% retransplantations. Eighty-two percent of patients developed at least 1 complication during 1-year follow-up. Biliary complications occurred in one-fifth of the patients up to 6 months after surgery. Benchmark cutoffs were ≤4 days for ICU stay, ≤18 days for hospital stay, ≤59% for patients with severe complications (≥ Grade III) and ≤42.1 for 1-year CCI. Comparisons with the next higher risk group (model for end stage liver disease 21-30) disclosed an increase in morbidity but within benchmark cutoffs for most, but not all indicators, while in patients receiving a second graft from 1 center (n = 50) outcome values were all outside of benchmark values. CONCLUSIONS: Despite excellent 1-year survival, morbidity in benchmark cases remains high with half of patients developing severe complications during 1-year follow-up. Benchmark cutoffs targeting morbidity parameters offer a valid tool to assess higher risk groups.

The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: A prospective validation study.

The selection of liver transplant candidates with hepatocellular carcinoma (HCC) relies mostly on tumor size and number. Instead of relying on these factors, we used poor tumor differentiation and cancer-related symptoms to exclude patients likely to have advanced HCC with aggressive biology. We initially reported similar 5-year survival for patients whose tumors exceeded (M+ group) and were within (M group) the Milan criteria. Herein, we validate our original data with a new prospective cohort and report the long-term follow-up (10-years) using an intention-to-treat analysis. The previously published study (cohort 1) included 362 listed (294 transplanted) patients from January 1996 to August 2008. The validation cohort (cohort 2) includes 243 listed (105 M+ group, 76 beyond University of California San Francisco criteria; 210 transplanted) patients from September 2008 to December 2012. Median follow-up from listing was 59.7 (26.8-103) months. For the validation cohort 2, the actuarial survival from transplant for the M+ group was similar to that of the M group at 1 year, 3 years, and 5 years: 94%, 76%, and 69% versus 95%, 82%, and 78% (P = 0.3). For the combined cohorts 1 and 2, there were no significant differences in the 10-year actuarial survival from transplant between groups. On an intention-to-treat basis, the dropout rate was higher in the M+ group and the 5-year and 10-year survival rates from listing were decreased in the M+ group. An alpha-fetoprotein level >500 ng/mL predicted poorer outcomes for both the M and M+ groups. CONCLUSION: Tumor differentiation and cancer-related symptoms of HCC can be used to select patients with advanced HCC who are appropriate candidates for liver transplantation; alpha-fetoprotein level limitations should be incorporated in the listing criteria for patients within or beyond the Milan criteria. (Hepatology 2016;64:2077-2088).

The influence of functional warm ischemia time on DCD liver transplant recipients' outcomes.

BACKGROUND: Duration of functional warm ischemia (f-WIT) is thought to have a causal effect on outcomes in controlled donation after circulatory death (DCD) liver transplantation (LT). METHODS: A retrospective cohort study was conducted at five centers. Data were extracted on donor and recipient characteristics, with attention to parameters recorded during withdrawal of life support to in situ cold perfusion. F-WIT was the time elapsed from any of the hemodynamic and oxygenation parameters to the start of in situ cold perfusion. Parameters were as follows: MAP ≤ 50 mm Hg; SBP ≤ 50 mm Hg; and SPO2 ≤ 60%. The primary endpoint was a composite of disseminated ischemic cholangiopathy (IC), primary non-function (PNF), and early graft failure. RESULTS: 35 patients (14%) developed one or more of the primary outcomes. On univariate analysis, older donors and longer WITs were associated with greater likelihood of complications. Of the f-WIT variations analyzed, only f-WIT with SpO2 ≤ 60% was longer among patients with complications. On multivariate analysis, only donor age was a significant predictor of complications. CONCLUSION: This study demonstrates that, of the f-WITs, f-WIT with SpO2 ≤ 60% is most predictive of post-DCD complications. However, results suggest that there may be an alternate etiology for poor outcomes, and that donor age plays a key role.

Normothermic ex vivo liver perfusion using steen solution as perfusate for human liver transplantation: First North American results.

The European trial investigating normothermic ex vivo liver perfusion (NEVLP) as a preservation technique for liver transplantation (LT) uses gelofusine, a non-US Food and Drug Administration-approved, bovine-derived, gelatin-based perfusion solution. We report a safety and feasibility clinical NEVLP trial with human albumin-based Steen solution. Transplant outcomes of 10 human liver grafts that were perfused on the Metra device at 37 °C with Steen solution, plus 3 units of erythrocytes were compared with a matched historical control group of 30 grafts using cold storage (CS) as the preservation technique. Ten liver grafts were perfused for 480 minutes (340-580 minutes). All livers cleared lactate (final lactate 1.46 mmol/L; 0.56-1.74 mmol/L) and produced bile (61 mL; 14-146 mL) during perfusion. No technical problems occurred during perfusion, and all NEVLP-preserved grafts functioned well after LT. NEVLP versus CS had lower aspartate aminotransferase and alanine aminotransferase values on postoperative days 1-3 without reaching significance. No difference in postoperative graft function between NEVLP and CS grafts was detected as measured by day 7 international normalized ratio (1.1 [1-1.56] versus 1.1 [1-1.3]; P = 0.5) and bilirubin (1.5; 1-7.7 mg/dL versus 2.78; 0.4-15 mg/dL; P = 0.5). No difference was found in the duration of intensive care unit stay (median, 1 versus 2 days; range, 0-8 versus 0-23 days; P = 0.5) and posttransplant hospital stay (median, 11 versus 13 days; range, 8-17 versus 7-89 days; P = 0.23). Major complications (Dindo-Clavien ≥ 3b) occurred in 1 patient in the NEVLP group (10%) compared with 7 (23%) patients in the CS group (P = 0.5). No graft loss or patient death was observed in either group. Liver preservation with normothermic ex vivo perfusion with the Metra device using Steen solution is safe and results in comparable outcomes to CS after LT. Using US Food and Drug Administration-approved Steen solution will avoid a potential regulatory barrier in North America. Liver Transplantation 22 1501-1508 2016 AASLD.

The significance of pre-operative coronary interventions on outcome after pancreas transplantation.

Pancreas transplant candidates are at very high risk of coronary vascular disease. We hypothesized that the requirement for pre-operative coronary intervention (PCI) may be associated with an adverse impact on short- and long-term outcomes. Retrospective analysis of 366 consecutive primary pancreas transplants was undertaken. Outcomes were compared between recipients who had undergone PCI (n = 48) and those who had not (n = 318). In 48% (23/48) of instances, the PCI was initiated by the transplant cardiology evaluation. The recipients undergoing PCI were older than those not undergoing PCI (47.6 yr vs. 41.9 yr, respectively, p < 0.0001). Although not statistically significant, there was a higher rate of post-operative major cardiovascular events (MCVE) in the PCI group (10.4%) compared with those not undergoing PCI (4.7%) (RR [95% CI]: 2.0 [0.90-4.5]; p = 0.17). In the long term, there were no differences in the rate of death with graft function (p = 0.77) or rejection (p = 0.17). There were no statistically significant differences between the groups with respect to patient (p = 0.54), kidney (p = 0.76), or pancreas (p = 0.63) graft survival. PCI is not a risk factor for short-term perioperative events, and long-term transplant outcomes are equivalent to patients not requiring PCI. PCI, by itself, should not be considered a contraindication for pancreas transplantation, but should raise awareness of perioperative risk.

Infiltrative (sinusoidal) and hepatitic patterns of injury in acute cellular rejection in liver allograft with clinical implications.

Acute cellular rejection post liver transplant occurs most commonly but not exclusively in the first year. In this study, we report two patterns: sinusoidal infiltrative and hepatitic, which are not considered in the Banff system. We describe their presentation, response to Solu-Medrol, and compare these to the typical moderate-severe acute cellular rejection. Patients transplanted from 2007 to 2012 at University Health Network, who had biopsy-proven rejection in the first year, were studied. Baseline transaminases and bilirubin, time of acute cellular rejection, follow-up, and treatment responses were analyzed. A total of 407 biopsies were received, of which 77 had diagnosis of acute cellular rejection with rejection activity index 5 or above; 49 from viral hepatitis patients were excluded. Twenty-eight were included; 15/28 (54%) had typical acute cellular rejection (tACR) using Banff criteria. Six (21%) had hepatitic acute cellular rejection overlapping with typical features of acute cellular rejection; seven (25%) had infiltrative acute cellular rejection (iACR) overlapping with typical features. The iACR occurred later than the tACR (124 versus 50 days; P = 0.032) and had a higher rise in baseline aspartate aminotransferase (ΔAST) compared with tACR (289 U/l versus 109 U/l; P=0.046). Only one out of seven patients with iACR (14 versus 40% in tACR) failed Solu-Medrol boluses and required thymoglobulin. Patients with hepatitic acute cellular rejection (hACR) had similar ΔAST (P = 0.12) but higher bilirubinemia than typical acute cellular rejection (tACR) (160 µmol/l versus 35 mol/l; P = 0.039) and required thymoglobulin in four out of six (67% versus 40%) instances. Patients with iACR had higher ΔAST than tACR but better Solu-Medrol response compared with both tACR and hACR. hACR is different from plasma cell-rich late-occurring cellular rejection in its pattern but similar in its poor Solu-Medrol response.

Outcomes of patients with cirrhosis and hepatorenal syndrome type 1 treated with liver transplantation.

Hepatorenal syndrome type 1 (HRS1) is acute renal failure in the setting of advanced cirrhosis, and it results from hemodynamic derangements, which should be fully reversible after liver transplantation. However, the rate of hepatorenal syndrome (HRS) reversal and factors predicting renal outcomes after transplantation have not been fully elucidated. The aim of this study was to assess outcomes of HRS1 patients after liver transplantation and factors predicting HRS reversal. A chart review of all liver transplant patients with HRS1 (according to International Ascites Club criteria) at Toronto General Hospital from 2001 to 2010 was conducted. Patient demographic data, pretransplant and posttransplant laboratory data, and the presence of and time to posttransplant HRS reversal (serum creatinine < 1.5 mg/dL) were extracted from the center's transplant electronic database. Patients were followed until death or the end of the 2011 calendar year. Sixty-two patients (mean age, 54.7 ± 1.2 years; mean Model for End-Stage Liver Disease score, 35 ± 1) with HRS1 (serum creatinine, 3.37 ± 0.13 mg/dL) at liver transplant were enrolled. Thirty-eight patients received midodrine, octreotide, and albumin without success and subsequently received renal dialysis. One further patient received dialysis without pharmacotherapy. After liver transplantation, HRS1 resolved in 47 of 62 patients (75.8%) at a mean time of 13 ± 2 days. Patients without HRS reversal had significantly higher pretransplant serum creatinine levels (3.81 ± 0.34 versus 3.23 ± 0.14 mg/dL, P = 0.06), a longer duration of HRS1 {25 days [95% confidence interval (CI), 16-42 days] versus 10 days (95% CI, 10-18 days), P = 0.02}, a longer duration of pretransplant dialysis [27 days (95% CI, 13-41 days) versus 10 days (95% CI, 6-14 days), P = 0.01], and increased posttransplant mortality (P = 0.0045) in comparison with those whose renal function recovered. The only predictor of HRS1 nonreversal was the duration of pretransplant dialysis with a 6% increased risk of nonreversal with each additional day of dialysis. In conclusion, our study suggests that patients with HRS1 should receive a timely liver transplant to improve their outcome.

Biliary complications in pediatric liver transplantation: Incidence and management over a decade.

This study analyzed how features of a liver graft and the technique of biliary reconstruction interact to affect biliary complications in pediatric liver transplantation. A retrospective analysis was performed of data collected from 2001 to 2011 in a single high-volume North American pediatric transplant center. The study cohort comprised 173 pediatric recipients, 75 living donor (LD) and 98 deceased donor (DD) recipients. The median follow-up was 70 months. Twenty-nine (16.7%) patients suffered a biliary complication. The majority of leaks (9/12, 75.0%) and the majority of strictures (18/22, 81.8%) were anastomotic. There was no difference in the rate of biliary complications associated with DD (18.4%) and LD (14.7%) grafts (P = 0.55). Roux-en-Y (RY) reconstruction was associated with a significantly lower rate of biliary complications compared to duct-to-duct reconstruction (13.3% versus 28.2%, respectively; P = 0.048). RY anastomosis was the only significant factor protecting from biliary complications in our population (hazard ratio, 0.30; 95% confidence interval, 0.1-0.85). The leaks were managed primarily by relaparotomy (10/12, 83.3%), and the majority of strictures were managed by percutaneous biliary intervention (14/22, 63.6%). Patients suffering biliary complications had inferior graft survival (P = 0.04) at 1, 5, and 10 years compared to patients without biliary complications. Our analysis demonstrates a lower incidence of biliary complications with RY biliary reconstruction, and patients with biliary complications have decreased graft survival.

Long-term follow-up of biliary complications after adult right-lobe living donor liver transplantation.

INTRODUCTION: Long-term biliary complications after living donor liver transplantation (LDLT) are not well described in the literature. This study was undertaken to determine the long-term impact of biliary complications after adult right-lobe LDLT. METHODS: This retrospective review analyzed an 11-yr experience of 344 consecutive right-lobe LDLTs with at least two yr of follow-up. RESULTS: Biliary leaks occurred in 50 patients (14.5%), and strictures occurred in 67 patients (19.5%). Cumulative biliary complication rates at 1, 2, 5, and 10 yr were 29%, 32%, 36%, and 37%, respectively. Most early biliary leaks were treated with surgical drainage (N = 29, 62%). Most biliary strictures were treated first with endoscopic retrograde cholangiography (42%). There was no association between biliary strictures and the number of ducts (hazard ratio [HR] 1.017 [0.65-1.592], p = 0.94), but freedom from biliary stricture was associated with a more recent era (2006-2010) (HR 0.457 [0.247-0.845], p = 0.01). Long-term graft survival did not differ between those who had or did not have biliary complications (66% vs. 67% at 10 yr). CONCLUSIONS: Biliary strictures are common after LDLT but may decline with a center's experience. With careful follow-up, they can be successfully treated, with excellent long-term graft survival rates.

Duodenal leaks after pancreas transplantation with enteric drainage - characteristics and risk factors.

Pancreas-kidney transplantation with enteric drainage has become a standard treatment in diabetic patients with renal failure. Leaks of the graft duodenum (DL) remain a significant complication after transplantation. We studied incidence and predisposing factors of DLs in both simultaneous pancreas-kidney (SPK) and pancreas after kidney (PAK) transplantation. Between January 2002 and April 2013, 284 pancreas transplantations were performed including 191 SPK (67.3%) and 93 PAK (32.7%). Patient data were analyzed for occurrence of DLs, risk factors, leak etiology, and graft survival. Of 18 DLs (incidence 6.3%), 12 (67%) occurred within the first 100 days after transplantation. Six grafts (33%) were rescued by duodenal segment resection. Risk factors for a DL were PAK transplantation sequence (odds ratio 3.526, P = 0.008) and preoperative immunosuppression (odds ratio 3.328, P = 0.012). In the SPK subgroup, postoperative peak amylase as marker of preservation/reperfusion injury and recipient pretransplantation cardiovascular interventions as marker of atherosclerosis severity were associated with an increased incidence of DLs. CMV-mismatch constellations showed an increased incidence in the SPK subgroup, however without significance probability. Long-term immunosuppression in PAK transplantation is a major risk factor for DLs. Early surgical revision offers the chance of graft rescue.

High preoperative bilirubin values protect against reperfusion injury after live donor liver transplantation.

Heme Oxygenase-1 and its product biliverdin/bilirubin have been demonstrated to protect against ischemia/reperfusion injury (IRI). We investigated whether increased preoperative bilirubin values of transplant recipients decrease IRI. Preoperative bilirubin levels of live donor liver recipients were correlated to postoperative liver transaminase as a marker of IRI. Additionally, two recipient groups with pretransplant bilirubin levels >24 µmol/l (n = 348) and ≤24 µmol/l (n = 118) were compared. Post-transplant liver function, complications, length of hospital stay, and patient and graft survival were assessed. Preoperative bilirubin levels were negatively correlated to the postoperative increase in transaminases suggesting a protective effect against IRI. The maximal rise of ALT after transplantation in high versus low bilirubin patients was 288 (-210-2457) U/l vs. 375 (-11-2102) U/l, P = 0.006. Bilirubin remained a significant determining factor in a multivariate linear regression analysis. The MELD score and its individual components as a marker of severity of chronic liver disease were significantly higher in the high versus low bilirubin group (P < 0.001). Despite this, overall complication rate (21.0% vs. 21.2%, P = 0.88), hospital stay [13 (4-260) vs. 14 (6-313) days, P = 0.93), and 1-year graft survival (90.8% vs. 89.0%, P = 0.62) were similar in both groups. High bilirubin levels of liver recipients before live donor transplantation is associated with decreased postoperative IRI.

Cytomegalovirus infection post-pancreas-kidney transplantation--results of antiviral prophylaxis in high-risk patients.

BACKGROUND: Cytomegalovirus (CMV) is a major pathogen affecting solid organ transplant (SOT) recipients. Prophylactic strategies have decreased the rate of CMV infection/disease among SOT. However, data on the effect of current prophylactic strategies for simultaneous pancreas-kidney (SPK) or pancreas after kidney (PAK) transplant remain limited. We report our experience of CMV prophylaxis in SPK/PAK recipients. METHODS: A total of 130 post-SPK/PAK patients were analyzed retrospectively for the rate of CMV and the risk factors associated with the acquisition of CMV. All patients received antiviral prophylaxis. The follow-up period was one yr post-transplant or until death. RESULTS: The rate of CMV post-SPK/PAK transplant was 24%, 44%, and 8.2% among the whole cohort, the D+/R- and the R+ groups, respectively. Median time of prophylaxis was 49 (0-254) d. In the whole cohort, risk factors for CMV infection/diseases were D+/R- CMV status (odds ratio [OR] = 16.075), preceding non-CMV (infection caused by bacteria or fungi and other viruses) infection (OR = 6.362) and the duration of prophylaxis (OR = 0.984). Among the CMV D+/R- group, non-CMV infection was the only risk factor for CMV disease (OR = 10.7). CONCLUSIONS: Forty-four per cent (25/57) of the D+/R- recipients developed CMV infection/disease despite CMV prophylaxis. Current CMV prophylaxis failed to prevent CMV infection/disease in this group of patients.

Response Evaluation Criteria in Solid Tumors (RECIST) criteria are superior to European Association for Study of the Liver (EASL) criteria at 1 month follow-up for predicting long-term survival in patients treated with transarterial chemoembolization before liver transplantation for hepatocellular cancer.

PURPOSE: To determine whether response to transarterial chemoembolization can predict survival in patients with hepatocellular carcinoma (HCC) who are candidates for orthotopic liver transplantation (LT) and if either European Association for Study of the Liver (EASL) criteria or Response Evaluation Criteria in Solid Tumors (RECIST) criteria are more accurate for this purpose. MATERIALS AND METHODS: A retrospective review of all patients who underwent LT after transarterial chemoembolization between January 2005 and June 2011 was performed. Follow-up imaging with multiphasic computed tomography or magnetic resonance imaging was performed 1 month after transarterial chemoembolization and every 3 months thereafter until LT. Treatment response was evaluated at each imaging time point using RECIST criteria and EASL criteria. The relationship between survival and objective response (OR), time to response (TTR), time to progression (TTP), and time interval between transarterial chemoembolization and LT was assessed. RESULTS: A median of one transarterial chemoembolization procedure was performed before LT in 58 patients (52 men, 6 women; mean age, 57 y). OR was shown by 28 (48%) patients and 51 (88%) patients at 1 month by EASL criteria and RECIST criteria, respectively. OR at 1-month follow-up using RECIST criteria was associated with increased survival compared with patients with no response (NR) (P = .03). Using RECIST criteria, 5-year survival in the OR group was 66.7% versus 0% in the NR group (P = .015). There was no significant difference in survival in patients who showed OR at 1 month using EASL criteria. There was poor agreement between RECIST and EASL response assessments (κ = 0.23). There was no significant association between survival and TTR, TTP, or time interval between transarterial chemoembolization and LT. CONCLUSIONS: Patients with objective response to transarterial chemoembolization at 1 month using RECIST criteria showed improved survival over nonresponders. RECIST criteria demonstrated better accuracy compared with EASL criteria for predicting survival in patients after LT who had transarterial chemoembolization as a "bridge."

The long-term efficacy of nucleos(t)ide analog plus a year of low-dose HBIG to prevent HBV recurrence post-liver transplantation.

Hepatitis B immunoglobulin (HBIG), given in combination with nucleos(t)ide therapy, has reduced the rate of recurrent hepatitis B virus (HBV) following liver transplantation (LT), although the most effective protocol is unknown. We have retrospectively evaluated the use of long-term nucleos(t)ide analog in combination with one yr of low-dose HBIG. One hundred and fifty-two adults with HBV-related liver disease underwent LT in our center from January 1999 to August 2009; of these, 132 patients who received one yr of HBIG combined with long-term nucleos(t)ide analogs (largely on lamivudine [LAM] alone, n = 97) afterward were included for the purposes of this study. Median follow-up post-transplantation was 1752 d. Patient survival was 93.9%, 86.9% and 84.1% at 1, 5, and 10 yr, respectively; none of the 17 deceased patients had recurrent HBV. HBV recurrence was observed in nine patients (all received LAM+HBIG), yielding recurrence rates of 2.3%, 5.1%, and 8.6% at 1, 3, and 5/10 yr, respectively. All recurrences were successfully managed, usually with additional antiviral treatment. In conclusion, this study, with its long-term follow-up, demonstrates that short course of low-dose HBIG (without anti-HBs monitoring) combined with the use of long-term nucleos(t)ide analog is effective and less cumbersome than many protocols in current use.

Retrospective study of the incidence and outcomes from lung cancer in solid organ transplant recipients.

OBJECTIVE: Organ transplant recipients (OTR) have an increased risk of developing post-transplant malignancies with lung cancer being one of the most common. In this retrospective study, we investigated incidence, use of systemic therapy and outcomes from lung cancer in OTR. MATERIALS AND METHODS: Patients diagnosed with lung cancer following a solid organ transplant at the University Health Network, Toronto, ON, CA, from January 1, 1980 to June 30, 2016 were included. Data for the study population, patient characteristics, treatments and outcomes were abstracted from solid OTR databases, our cancer registry and patient charts. Univariate Kaplan-Meier curves estimated median overall survival (OS) by histology, stage and systemic therapy. RESULTS: Amongst 7944 OTR (heart [N = 765], lung [n = 1668], liver [n = 2238], kidney [n = 3273]), 101 (1.3 %) developed lung cancer which were included in our analyses. Of these, 81 % were non-small cell lung cancer (NSCLC), 11 % small cell lung cancer (SCLC) and 8% neuroendocrine tumor (NET). Median OS (months) was 25 in those that presented with Stage I/II NSCLC (44 %); 25 for Stage III NSCLC (7%); 3 for Stage IV NCLC (31 %); 10 for Limited stage SCLC (6%); 2 for Extensive stage (ES) SCLC (5%). NSCLC patients that received palliative chemotherapy had an OS of 8 months; ES-SCLC patients that received chemotherapy had an OS of 6 months. Of all patients who received platinum doublets (n = 16), 10 (62.5 %) required dose reductions at some point. Five patients experienced febrile neutropenia (31 %); two (12 %) had other toxicities leading to discontinuation. CONCLUSION: Patients with stage I/II NSCLC and NET had poorer survival compared to historical norms in non-transplant patients. Patients who had stage III NSCLC or received palliative systemic therapy had survivals at or slightly below historic norms, although numbers were small. Chemotherapy can be administered in selected OTR patients though dose reductions and febrile neutropenia were common.

Elevated Preoperative Serum Bilirubin Improves Reperfusion Injury and Survival Postliver Transplantation.

BACKGROUND: The cytoprotective effects of hemeoxygenase-1 and its product biliverdin/bilirubin are widely acknowledged in experimental transplant medicine. However, its potentially beneficial effect during organ reperfusion is not established. METHODS: In a matched study, we compared markers of reperfusion injury (alanine aminotransferase/aspartate aminotransferase) and transplantation outcome (complication rates, liver function, and survival) between recipient groups with "normal" versus "increased" preoperative bilirubin values. Groups were matched for donor and recipient age, liver disease, year of transplantation, and recipient's preoperative condition (modified model for end-stage liver disease score excluding bilirubin). RESULTS: The postoperative transaminase peak was significantly higher when comparing the "normal" to the "increased" bilirubin group (maximum aspartate aminotransferase "normal" 2013 [325-13 210] U/L vs "increased" 1360 [221-15 460] U/L, P = 0.006; maximum alanine aminotransferase "normal" 1151 [82-6595] U/L vs "increased" 820 [66-5382] U/L, P = 0.01). Grafts in the "increased" bilirubin group had faster recovery of graft function with faster decrease in international normalized ratio at days 3 and 7 posttransplantation in the "increased" vs "normal" bilirubin group. Although long-term functional parameters (international normalized ratio and bilirubin posttransplantation) as well as surgical and biliary complication rates were similar in both groups, 1-year survival rates were significantly higher in the group with increased preoperative bilirubin (graft survival, "normal" 86% vs "increased" 97%; P = 0.006). CONCLUSIONS: Increased bilirubin levels of liver graft recipients before transplantation are associated with reduced reperfusion injury and improved survival after transplantation.

Preserving the Pancreas Graft: Outcomes of Surgical Repair of Duodenal Leaks in Enterically Drained Pancreas Allografts.

BACKGROUND: Duodenal leak remains a major cause of morbidity and graft loss in pancreas transplant recipients. The role and efficacy of surgical and image-guided interventions to salvage enterically drained grafts with a duodenal leak has yet to be defined. METHODS: We investigated the incidence, treatment, and outcome of duodenal leak in 426 pancreas transplantation recipients from 2000 to 2015. RESULTS: Duodenal leak developed in 33 (7.8%) recipients after a median follow-up of 5.3 (range, 0.5-15.2) years. Most leaks occurred during the first year (n = 22; 67%), and most were located near the proximal and distal duodenal staple line. Graft pancreatectomy was performed in 8 patients as primary therapy because of unfavorable local and/or systemic conditions. Salvage was attempted in 25 patients using percutaneous drainage (n = 4), surgical drainage (n = 4), or surgical repair (n = 17). Percutaneous or surgical drainage failed to control the leak in 7 of these 8 patients, and all 7 ultimately required graft pancreatectomy for persistent leak and sepsis. Surgical repair salvaged 14 grafts, and 13 grafts continue to function after a median follow-up of 2.9 (range, 1.1-6.3) years after repair. CONCLUSIONS: Our study shows that in selected patients a duodenal leak can be repaired successfully and safely in enterically drained grafts.

Pretransplant Type 2 Hepatorenal Syndrome Is Associated With Persistently Impaired Renal Function After Liver Transplantation.

BACKGROUND: Type 2 hepatorenal syndrome (HRS2) is a functional renal impairment complicating end-stage liver disease. Although it is reversible after liver transplantation, long-term posttransplant outcomes in HRS2 patients remain ill-defined. METHODS: Retrospective, matched case-control (1:2) study of all adult HRS2 patients transplanted in our institution between 2000 and 2012. The HRS2 patients were identified from our electronic transplant database, and matched with controls for the following variables: age, sex, etiology, diabetes mellitus, and year of transplant. RESULTS: Forty-two HRS2 patients were compared to 83 controls. At the time of transplant, HRS2 patients had an estimated glomerular filtration rate of 41 ± 1 mL/min per 1.73 m. The HRS2 patients had greater intraoperative packed red blood cell transfusion (P = 0.002), and longer intensive care unit (P = 0.01) as well as total hospital length of stay (P = 0.03). Reversal of HRS2 occurred in 88.1% patients, 5.7 ± 0.5 days after transplantation. Although HRS2 patients had lower initial exposure to calcineurin inhibitors, a greater proportion of HRS2 patients had chronic kidney disease stage 3 (CKD3) at 3 (53.8% vs 28.4%; P = 0.007) and 12 months (59.5% vs 38.2%; P = 0.03) compared to controls. One-year survival was similar between the 2 groups (log-rank P = 0.82). On multivariate analysis, pretransplant HRS2 was associated with CKD3 at 3 (odds ratio, 3.73; 95% confidence interval, 1.54-9.03; P = 0.004) and 12 months (odds ratio, 3.23; 95% confidence interval, 1.37-7.64; P = 0.007) after transplantation. CONCLUSIONS: Liver transplantation reverses HRS2 in the majority of patients with survival outcomes comparable to matched controls, despite longer stays in intensive care unit and in hospital. Pretransplant HRS2 is associated with early posttransplant CKD3, despite calcineurin-inhibitor minimization.

Post-transplant lymphoproliferative disorder in liver recipients: Characteristics, management, and outcome from a single-centre experience with >1000 liver transplantations.

BACKGROUND: The literature regarding post-transplant lymphoproliferative disorder (PTLD) in liver transplant recipients (LTRs) is limited. OBJECTIVES: To study the incidence, predictors and outcomes of PTLD after liver transplantation in a single, large-volume centre. METHODS: The charts of all LTRs (n=1372) in the authors' centre between January 2000 and June 2012 were retrospectively reviewed and those who developed PTLD were identified. Demographic, clinical and treatment data were prospectively collected. Responses to treatment, including complete response, no response, relapse and survival, were recorded. RESULTS: The incidence of PTLD in LTRs was 32 in 1372 (2.3%). Overall, median survival was 37 months (range 0.5 to 195 months), with one-, three- and five-year survival rates of 81%, 74% and 60%, respectively. Epstein-Barr virus (EBV)-negative patients had a better mean (± SD) survival (95±79 months) than EBV-positive patients (41±42 months) (P=0.02). For stage I/II PTLD, one-, three- and five-year actuarial survival was 87%, 87% and 75%, compared with 50%, 30% and 0% for stage III/IV PTLD, respectively (P=0.001). In patients with complete response, median survival was 58 months (range 10 to 195 months); and one-, three- and five-year actuarial survival was 100%, 94% and 76%, respectively, after diagnosis of PTLD. Changing immunosuppression (IS) from calcineurin inhibitor to sirolimus at the time of diagnosis may have improved survival (seven of seven survivors) compared with only decreasing or stopping IS (14 of 25 survivors) (P=0.07). CONCLUSIONS: This series from a single large-volume centre showed excellent short and long-term survival after PTLD in adult LTRs who were EBV negative, had early disease and showed complete response. Consistent with the known in vitro antiproliferative effect of sirolimus, switching IS from calcineurin inhibitor to sirolimus may improve survival.

High sustained virological response to pegylated interferon and ribavirin for recurrent genotype 3 hepatitis C infection post-liver transplantation.

INTRODUCTION: Treatment outcomes of recurrent HCV genotype 3 (GT-3) after liver transplantation (LT) are ill-defined. AIMS: To determine efficacy, predictors, and long-term survival after treatment of recurrent HCV GT-3 infection, post-LT, with a combination of pegylated interferon (PEG) and ribavirin (RBV). METHODS: We studied all LT recipients (LTR) in our program treated with PEG and RBV for recurrent HCV GT-3 between Jan 1st 2002 and Dec 31st 2013. Antiviral therapy (AVT) was started if histology showed recurrent HCV with ≥ stage 2 fibrosis. Treatment was intended for 24 or 36 weeks, depending on early virologic response, and/or 24 weeks consolidation. Primary endpoint was sustained virological response (SVR). We also studied predictors of SVR and long-term patient survival. RESULTS: Among 492 LT for HCV-related cirrhosis and/or hepatocellular carcinoma performed during the study period, 110 (22%) had HCV GT-3 infection. Fifty-two (10.5%) HCV GT-3 patients had indications for AVT. Six were unable to complete the AVT, three because of clinical decompensation and one each because of metastatic disease involving the brain, lung cancer, and ductopenic rejection. Forty-seven (90%) patients achieved early virological response (EVR) and 37 (71%) achieved SVR. Predictors of SVR were EVR (p < 0.001), stage ≤ 3 fibrosis (p = 0.008), and 36 weeks treatment duration (p < 0.001). Less advanced fibrosis ≤ 3 was independent predictor of SVR (OR 0.18, 95% CI 0.05-0.67). SVR patients had actuarial (Kaplan-Meier) 1, 3, and 10 year post-treatment survival of 100, 100, and 95%, compared with 87, 78, and 20% for non-SVR patients (p < 0.001, log rank test). CONCLUSION: Efficacy of AVT for recurrent HCV GT-3 post-LT is high, and comparable with that for non-transplant patients. Less advanced fibrosis is an independent predictor of SVR. SVR improves long-term survival.