Steroid pretreatment of deceased donors and liver allograft function - Ten years follow-up of a blinded randomized placebo controlled trial.

BACKGROUND: Within the last decade numerous attempts have been reported in order to expand the donor pool and alleviate organ shortage in the setting of liver transplantation. Aim of this blinded randomized controlled trial was to evaluate the effect of donor steroid pretreatment on outcomes after liver transplantation. METHODS: We performed an international, multi-center double-blinded randomized placebo controlled trial. Donors received 1000 mg methylprednisone or placebo before organ procurement. Primary endpoint were patient and graft survival. Secondary end points were rate of BPAR and liver functions trajectories after transplantation. Follow up was 10 years. RESULTS: There was no effect of steroid pretreatment vs. placebo on overall patient survival (50% vs. 46%, p = n.s.) as well as graft survival (47% vs. 51%, p= n.s.). Further donor steroid pretreatment did not alter the rate of biopsy proven acute rejections (34% steroid group vs. 36% placebo, p = n.s.). Evaluating short term and long term graft function, steroid pretreatment had minor effect on immediate liver function trajectories within the first 2 weeks after transplantation. This was not seen in long-term follow up. CONCLUSION: In conclusion we found no evidence that donor steroid pretreatment translates in improved outcomes after liver transplantation.

The von Willebrand Factor Facilitates Model for End-Stage Liver Disease-Independent Risk Stratification on the Waiting List for Liver Transplantation.

BACKGROUND AND AIMS: The Model for End-Stage Liver Disease (MELD) is used for clinical decision-making and organ allocation for orthotopic liver transplantation (OLT) and was previously upgraded through inclusion of serum sodium (Na) concentrations (MELD-Na). However, MELD-Na may underestimate complications arising from portal hypertension or infection. The von Willebrand factor (vWF) antigen (vWF-Ag) correlates with portal pressure and seems capable of predicting complications in patients with cirrhosis. Accordingly, this study aimed to evaluate vWF-Ag as an adjunct surrogate marker for risk stratification on the waiting list for OLT. APPROACH AND RESULTS: Hence, WF-Ag at time of listing was assessed in patients listed for OLT. Clinical characteristics, MELD-Na, and mortality on the waiting list were recorded. Prediction of 3-month waiting-list survival was assessed by receiver operating characteristics and net reclassification improvement. Interestingly, patients dying within 3 months on the waiting list displayed elevated levels of vWF-Ag (P < 0.001). MELD-Na and vWF-Ag were comparable and independent in their predictive potential for 3-month mortality on the waiting list (area under the curve [AUC], vWF-Ag = 0.739; MELD-Na = 0.764). Importantly, a vWF-Ag cutoff at 413% identified patients at risk for death within 3 months of listing with a higher odds ratio (OR) than the previously published cutoff at a MELD-Na of 20 points (vWF-Ag, OR = 10.873, 95% confidence interval [CI], 3.160, 36.084; MELD-Na, OR = 7.594, 95% CI, 2.578, 22.372; P < 0.001, respectively). Ultimately, inclusion of vWF-Ag into the MELD-Na equation significantly improved prediction of 3-month waiting-list mortality (AUC, MELD-Na-vWF = 0.804). CONCLUSIONS: A single measurement of vWF-Ag at listing for OLT predicts early mortality. Combining vWF-Ag levels with MELD-Na improves risk stratification and may help to prioritize organ allocation to decrease waiting-list mortality.

Preoperative ultrasound improves patency and cost effectiveness in arteriovenous fistula surgery.

OBJECTIVE: We aimed to compare routine preoperative color-coded duplex ultrasound (DUS) to clinical examination (CE) alone in surgery for arteriovenous fistula (AVF) with special emphasis on long-term outcomes and cost effectiveness. METHODS: All patients undergoing an AVF formation or revision between January 1, 2011, and December 31, 2016, at our tertiary referral center were subject to analysis. Routine DUS was performed in 114 patients and CE alone in 217 patients. Primary and secondary patency, the need for revision or reintervention to obtain patency, and individual as well as overall costs were analyzed. RESULTS: Primary patency rate was higher in AVF after DUS compared with CE alone at 62% vs 26% (P < .05), respectively. Patients receiving DUS had significantly lower rates of revision and revisions per patient when compared with CE (25.4% vs 59.4% [P < .0001]; 0.36 ± 0.71 vs 1.06 ± 1.55 [P < .0001], respectively). Costs per patient were significantly lower in the DUS group compared with CE at 4074€ vs 6078€ (P < .0001). CONCLUSIONS: We were able to show that patients receiving preoperative DUS showed higher patency rates and needed fewer revisions. Standard preoperative ultrasound examination is an easy tool to improve outcomes and cost effectiveness in AVF surgery.

A systematic review and meta-analysis of rescue revascularization with arterial conduits in liver transplantation.

Although aortohepatic conduits (AHCs) provide an effective technique for arterialization in liver transplantation (LT) when the native recipient artery is unusable, various publications report higher occlusion rates and impaired outcome compared to conventional anastomoses. This systematic review and meta-analysis investigates the published evidence of outcome and risk of AHCs in LT using bibliographic databases and following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Primary and secondary outcome were artery occlusion as well as graft and patient survival. Twenty-three retrospective studies were identified with a total of 22 113 patients with LT, of whom 1900 patients (9%) received an AHC. An AHC was used in 33% of retransplantations. Early artery occlusion occurred in 7% (3%-16%) of patients with AHCs, compared to 2% (1%-3%) without conduit (OR 3.70; 1.63-8.38; P = .001). The retransplantation rate after occlusion was not significantly different in both groups (OR 1.46; 0.67-3.18; P = .35). Graft (HR 1.38; 1.17-1.63; P < .001) and patient (HR 1.57; 1.12-2.20; P = .009) survival was significantly lower in the AHC compared to the nonconduit group. In contrast, graft survival in retransplantations was comparable (HR 1.00; 0.82-1.22; P = .986). Although AHCs provide an important rescue option, when regular revascularization is not feasible during LT, transplant surgeons should be alert of the potential risk of inferior outcome.

Outcome after liver transplantation in elderly recipients (>65 years) - A single-center retrospective analysis.

BACKGROUND: Liver transplantation (LT) in elderly recipients is controversially discussed in the literature with only little data on long-term outcome available. We aimed to evaluate the safety and efficiency of LT in elderly recipients (>65 years). METHODS: Between 1989-2016, 139 patients >65 years-old were listed for liver transplantation, and 76 (55%) were transplanted. Patient outcome and characteristics were evaluated separately for the time period before (1989-2004) and after (2005-2016) MELD-implementation. Post-transplant outcome was compared between the elderly cohort and LT-recipients aged 18-65 years (n = 1395). RESULTS: Overall survival of patients >65 years was better in the MELD-era compared to the earlier period (1- and 5-year-survival: 73%, 60% vs. 69%, 37%, respectively; p = 0.055). The main differences between the two groups included higher recipient age (p = 0.001) and BMI (p = 0.001), higher donor age (p < 0.001), less need of intraoperative red blood cells (p = 0.008) and a lower number of postoperative rejections (p = 0.03) after 2004. Comparing the overall survival of patients transplanted in the MELD-era aged 18-65 years vs. >65 years displayed comparable 1- and 5 year-survival rates (81%, 68% vs. 73% and 60%, respectively, p = 0.558). CONCLUSION: In the modern era, outcome of patients receiving LT with >65 years is comparable to <65 year-old patients. After careful evaluation, patients >65 years old should be considered for LT.

Multimodality locoregional treatment strategies for bridging HCC patients before liver transplantation.

BACKGROUND: It is current practice that patients with hepatocellular carcinoma (HCC) listed for liver transplantation should receive locoregional treatment if the suspected waiting time for transplantation is longer than 6 months, even in the absence of prospective randomized data. Aim of this study was the comparison of single versus multimodality locoregional treatment strategies on outcomes after liver transplantation. METHODS: This is a retrospective analysis of 150 HCC patients listed for liver transplantation at our center between 2004 and 2011. Outcomes were analyzed according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) in relation to intention-to-treat and overall survival after liver transplantation. RESULTS: Overall, 92 patients (63%) were transplanted in this cohort. The intention-to-treat 1­, 3­, 5­year waiting list survival was 80, 59, and 50% respectively. In RFA-(radiofrequency ablative) and TACE-(transarterial chemoembolisation)-based regimens, rates of transplanted patients were comparable (69 vs. 58%, p = ns). No difference was seen in overall survival after liver transplantation when comparing TACE- and RFA-based regimens. Patients receiving multimodality locoregional therapy had lower overall survival after transplantation (p = 0.05). CONCLUSION: TACE- and RFA-based regimens showed equal outcomes in terms of transplantation rate, tumor response, and post-transplant survival. Patients in need of more than one treatment modality might identify a cohort with poorer post-transplant survival. POINTS OF NOVELTY: Direct comparison of TACE and RFA in a multimodality setting, analysis according to mRECIST.

Endoscopic versus surgical management of biliary complications - Outcome analysis after 1188 orthotopic liver transplantations.

BACKGROUND AND AIM: After liver transplantation, the endoscopic approach has become the standard treatment modality for biliary complications. Aim of this study was to compare primary endoscopic with primary surgical management. PATIENTS AND METHODS: A retrospective review on 1188 consecutive liver transplant patients between 1989 and 2009 was performed. Management strategies (endoscopic, surgical or combined approach) were evaluated for treatment success as well as patient survival. RESULTS: Biliary complications after liver transplantation were diagnosed in 211 (18%) patients. Initial endoscopic approach (N=162, 77%) was successful in 97 of 162 (60%) patients. In 80% of patients, success was achieved within a median of four ERCPs. Sixty-one patients (38%) were referred to surgery after non-successful ERCP. Initial surgical approach was performed in 49/211 patients (23%) with successful management in 38/49 (78%) of patients. Patients presenting with intraluminal objects needed a significantly higher number of ERCPs to reach treatment success (median 3 versus 2 interventions, p=0.001) but had an equal endoscopic success rate (p=0.427). Patients with successful endoscopic treatment showed lower mortality compared to patients with primary surgical treatment (p=0.029). CONCLUSIONS: Endoscopic management should be considered as the primary approach for biliary complications after liver transplantation.

Impact of dynamic changes in MELD score on survival after liver transplantation - a Eurotransplant registry analysis.

BACKGROUND & AIMS: With restricted numbers of available organs, futility in liver transplantation has to be avoided. The concept of dynamic changes in MELD score (DeltaMELD) has previously been shown to be a simple tool to identify patients with the greatest risk of death after transplantation. Aim was to validate this concept with the Eurotransplant (ET) database. METHODS: A retrospective registry analysis was performed on all patients listed for liver transplantation within ET between 2006 and 2011. Patients <18 years of age, acute liver failure, malignancy and patients listed for retransplantation were excluded. Influence of MELD at listing (MELDon), MELD at transplantation (MELDoff), DeltaMELD, age, sex, underlying disease and time on the waiting list on overall survival after liver transplantation were evaluated. RESULTS: A total of 16 821 patients were listed for liver transplantation, 8096 met the inclusion criteria. Age, MELD on and DeltaMELD showed significant influence on survival on the waiting list. Age and DeltaMELD showed influence on survival after liver transplantation, with DeltaMELD>10 showing a 1.6-fold increased risk of death. CONCLUSION: The concept of DeltaMELD was validated in a large, prospective data set. It provides a simple tool to identify patients with increased risk of death after liver transplantation and might help improve long-term results.

Dynamic changes in MELD score not only predict survival on the waiting list but also overall survival after liver transplantation.

The predictive value of MELD score for post-transplant survival has been under constant debate since its implementation in 2001. Aim of this study was to assess the impact of alterations in MELD score throughout waiting time (WT) on post-transplant survival. A single-centre retrospective analysis of 1125 consecutive patients listed for liver transplantation between 1997 and 2009 was performed. The impact of MELD score and dynamic changes in MELD score (DeltaMELD), as well as age, sex, year of listing and WT were evaluated on waiting list mortality and post-transplant survival. In this cohort, 539 (60%) patients were transplanted, 223 (25%) died on list and 142 (15%) were removed from the waiting list during WT. One-, three- and five-year survival after liver transplantation were 83%, 78% and 76% respectively. DeltaMELD as a continuous variable proved to be the only significant risk factor for overall survival after liver transplantation (hazard ratio (HR): 1.06, 95% confidence interval (CI) 1.02-1.1, P = 0.013). The highest risk of post-transplant death could be defined for patients with a DeltaMELD > 10 (HR: 4.87, 95% CI 2.09-11.35, P < 0.0001). In addition, DeltaMELD as well as MELD at listing showed a significant impact on waiting list mortality. DeltaMELD may provide an easy evaluation tool to identify patients on the liver transplant waiting list with a high mortality risk after transplantation in the current setting. Temporarily withholding and re-evaluating these patients might improve overall outcome after liver transplantation.