Wojciech G. Polak

First Comparison of Hypothermic Oxygenated PErfusion Versus Static Cold Storage of Human Donation After Cardiac Death Liver Transplants: An International-matched Case Analysis.

BACKGROUNDnExposure of donor liver grafts to prolonged periods of warm ischemia before procurement causes injuries including intrahepatic cholangiopathy, which may lead to graft loss. Due to unavoidable prolonged ischemic time before procurement in donation after cardiac death (DCD) donation in 1 participating center, each liver graft of this center was pretreated with the new machine perfusion Hypothermic Oxygenated PErfusion (HOPE) in an attempt to improve graft quality before implantation.nnnMETHODSnHOPE-treated DCD livers (nu200a=u200a25) were matched and compared with normally preserved (static cold preservation) DCD liver grafts (nu200a=u200a50) from 2 well-established European programs. Criteria for matching included duration of warm ischemia and key confounders summarized in the balance of risk score. In a second step, perfused and unperfused DCD livers were compared with liver grafts from standard brain dead donors (nu200a=u200a50), also matched to the balance of risk score, serving as baseline controls.nnnRESULTSnHOPE treatment of DCD livers significantly decreased graft injury compared with matched cold-stored DCD livers regarding peak alanine-aminotransferase (1239 vs 2065u200aU/L, Pu200a=u200a0.02), intrahepatic cholangiopathy (0% vs 22%, Pu200a=u200a0.015), biliary complications (20% vs 46%, Pu200a=u200a0.042), and 1-year graft survival (90% vs 69%, Pu200a=u200a0.035). No graft failure due to intrahepatic cholangiopathy or nonfunction occurred in HOPE-treated livers, whereas 18% of unperfused DCD livers needed retransplantation. In addition, HOPE-perfused DCD livers achieved similar results as control donation after brain death livers in all investigated endpoints.nnnCONCLUSIONSnHOPE seems to offer important benefits in preserving higher-risk DCD liver grafts.

Liver transplantation with preservation of the inferior vena cava. A comparison of conventional and piggyback techniques in adults

Abstract:u2002 The aim of this study is to analyse a single centres experience with two techniques of liver transplantation (OLT), conventional (CON‐OLT) and piggyback (PB‐ES), and to compare outcome in terms of survival, morbidity, mortality and post‐operative liver function as well as operative characteristics. A consecutive series (1994–2000) of 167 adult primary OLT were analysed. Ninety‐six patients had CON‐OLT and 71 patients had PB‐ES. In PB‐ES group two revascularization protocols were used. In the first protocol reperfusion of the graft was performed first via the portal vein followed by the arterial anastomosis (PB‐seq). In the second protocol the graft was reperfused simultaneously via portal vein and hepatic artery (PB‐sim). One‐, 3‐ and 5‐yr patient survival in the CON‐OLT and PB‐ES groups were 90, 83 and 80%, and 83, 78 and 78%, respectively (pu2003=u2003ns). Graft survival at the same time points was 81, 73 and 69%, and 78, 69 and 65%, respectively (pu2003=u2003ns). Apart from the higher number of patients with cholangitis and sepsis in CON‐OLT group, morbidity, retransplantation rate and post‐operative liver and kidney function were not different between the two groups. The total operation time was not different between both groups (9.4u2003h in PB‐ES vs. 10.0u2003h in CON‐OLT), but in PB‐ES group cold and warm ischaemia time (CIT and WIT), revascularization time (REVT), functional and anatomic anhepatic phases (FAHP and AAHP) were significantly shorter (8.9u2003h vs. 10.7u2003h, 54u2003min vs. 63u2003min, 82u2003min vs. 114u2003min, 118u2003min vs. 160u2003min and 87u2003min vs. 114u2003min, respectively, pu2003<u20030.05). RBC use in the PB‐ES group was lower compared to the CON‐OLT group (4.0u2003min vs. 10.0 units, pu2003<u20030.05). Except for WIT and REVT there were no differences in operative characteristics between PB‐Sim and PB‐Seq groups. The WIT was significantly longer in PB‐Sim group compared with PB‐Seq group (64u2003min vs. 50u2003min, pu2003<u20030.05); however REVT was significantly shorter in PB‐Sim group (64u2003min vs. 97u2003min, pu2003<u20030.05). Results of this study show that both techniques are comparable in survival and morbidity; however PB‐ES results in shorter AAHP, FAHP, REVT and WIT as well as less RBC use. In the PB‐ES group there seems to be no adavantage for any of the revascularization protocols.

Sequential and simultaneous revascularization in adult orthotopic piggyback liver transplantation

The aim of the study was to assess whether there is a difference in outcome after sequential or simultaneous revascularization during orthotopic liver transplantation (OLT) in terms of patient and graft survival, mortality, morbidity, and liver function. The study population consisted of 102 adult patients with primary full‐size piggyback OLT transplanted between January 1998 and December 2001. In 71 patients (70%) the grafts were sequentially reperfused after completion of the portal vein anastomosis and subsequent arterial reconstruction was performed (sequential reperfusion [SeqR] group). In 31 patients (30%) the graft was reperfused simultaneously via the portal vein and hepatic artery (simultaneous reperfusion [SimR] group). Patient and graft survival at 1, 3, and 6 months and at 1 year did not differ between the SeqR group and the SimR group. The red blood cell (RBC) requirements were significantly higher in the SimR group (5.5 units; range 0‐20) in comparison to the SeqR group (2 units; range 0‐19) (P = 0.02). Apart from a higher number of biliary anastomotic complications and abdominal bleeding complications in the SimR group in comparison to the SeqR group (13% vs. 2% and 19% vs. 6%, respectively; P = 0.06), morbidity was not different between the groups. No differences between the groups were observed regarding the incidence of primary nonfunction (PNF), intensive care unit stay, and acute rejection. This was also true for the severity of rejections. Postoperative recuperation of liver function was not different between the groups. In conclusion, no advantage of either of the 2 reperfusion protocols could be observed in this analysis, especially with respect to the incidence of ischemic type biliary lesions (ITBL). (Liver Transpl 2005;11:934–940.)

Long-Term Results of Urgent Revascularization for Hepatic Artery Thrombosis After Pediatric Liver Transplantation

Hepatic artery thrombosis (HAT) after pediatric orthotopic liver transplantation (OLT) is a serious complication resulting in bile duct necrosis and often requiring retransplantation. Immediate surgical thrombectomy/thrombolysis has been reported to be a potentially successful treatment for restoring blood flow and avoiding urgent retransplantation. The long‐term results of this strategy remain to be determined. In 232 pediatric liver transplants, we analyzed long‐term outcomes after urgent revascularization for early HAT. HAT developed in 32 patients (13.7%). In 16 children (50%), immediate surgical thrombectomy was performed in an attempt to salvage the graft. Fourteen patients (44%) underwent urgent retransplantation, and 2 (6%) died before further intervention. Immediate thrombectomy resulted in long‐term restoration of the hepatic artery flow in 6 of 16 patients (38%) and in 1‐ and 5‐year graft and patient survival rates of 83% and 67%, respectively. In 10 patients, revascularization was unsuccessful, and retransplantation was inevitable. The 1‐ and 5‐year patient survival rates in this group decreased to 50% and 40%, respectively. After immediate retransplantation, the 5‐year patient survival rate was 71%. In conclusion, immediate surgical thrombectomy for HAT after pediatric OLT results in long‐term graft salvage in about one‐third of patients. However, when thrombectomy is unsuccessful, long‐term patient survival is lower than the survival of patients who underwent immediate retransplantation. Liver Transpl 16:847–855, 2010.

The sequence of revascularization in liver transplantation : It does make a difference

No consensus exists regarding the most optimal sequence of revascularization of the liver graft during liver transplantation. The current methods of revascularization of the liver graft can be divided into 2 main groups (Table 1). The first group is sequential revascularization, in which the graft is first reperfused via either the portal vein or the hepatic artery (anterograde reperfusion), or via the inferior vena cava (IVC) (retrograde reperfusion), with subsequent reconstruction of the remaining vessels. The second group is simultaneous revascularization, in which the graft is reperfused simultaneously via the portal vein and hepatic artery. Experimental as well as clinical studies comparing different methods of revascularization are still scarce, results are not always unequivocal, and endpoints differ largely between different studies. Nevertheless, some important messages can be extracted from the current literature.

Increased alpha-fetoprotein serum level is predictive for survival and recurrence of hepatocellular carcinoma in non-cirrhotic livers

Background: Hepatocellular carcinoma (HCC) may be diagnosed in the absence of cirrhosis. However, little is known about prognostic factors for the survival of HCC patients with a non-cirrhotic liver in the absence of well-established risk factors. Method: Survival rates and risk factors for survival and recurrence were analysed in all patients diagnosed between 2000 and 2010 with HCC in a non-cirrhotic liver and in the absence of well-established risk factors. Results: Ninety-four patients were analysed. Treatment with curative intent consisted of surgical resection in 43 patients (46%) and radiofrequency ablation in 4 patients (4%). In patients treated with curative intent and alive 30 days after treatment (n = 40), 1- and 5-year overall survival rates were 95 and 51%, respectively. Patients with a high preoperative α-fetoprotein (AFP) serum level, the presence of microvascular invasion in the resected specimen, a complicated postoperative course and a major resection, due to a greater tumour volume, had a significantly worse outcome and a higher recurrence rate. In multivariate analysis, a high AFP serum level at presentation was significantly associated with recurrence and a worse survival. Conclusion: HCC presenting in a non-cirrhotic liver in the absence of well-established risk factors has a poor prognosis. Increased AFP serum levels are significantly associated with clinical outcome.

Comparison of Postoperative Outcomes Between Donation After Circulatory Death and Donation After Brain Death Liver Transplantation Using the Comprehensive Complication Index

Objective: To test the total burden of complications in the early postoperative period after liver transplantation (LT) between donation after circulatory death (DCD) and donation after brain death (DBD) grafts with the novel Comprehensive Complication Index (CCI). Background: LT is complex surgery and the increasing use of high-risk grafts is pressuring current postoperative outcomes. DCD grafts in particular are associated with ischemic-type biliary lesions (ITBL) with subsequent impaired graft survival rates. Methods: Retrospective single-center study of all LT since the start of DCD program (2001–2015). CCI (at hospital discharge and after 6 months) was the result of all complications weighted by their Clavien-Dindo grade. A multiple logistic regression model was used to identify factors associated with a complex postoperative course (CCI at 6 months >60). Results: In total, 441 cases were included: 115 DCD and 326 DBD grafts. Median in-hospital CCI was comparable for both groups (DCD 38.2; DBD 36.7; P = 0.429). Six-month postoperative median CCI was significantly higher for DCD grafts (53.4 vs 47.2; P = 0.041). Moreover, more DCD recipients underwent retransplantation for ITBL in this period (4% vs 1%; P = 0.031). Logistic regression identified recipient BMI (P = 0.046), recipient warm ischemia time (odds ratio, OR, 1.032; 95% CI, 1.008–1.056; P = 0.008), and DCD graft (OR 3.913; 95% CI 1.200–12.767; P = 0.024) as risk factors for a CCI >60. Conclusions: This analysis shows a comparable complication rate during the index hospital stay for DCD and DBD LT, but the CCI increases significantly for DCD recipients in 6 months after transplantation. Reduction of biliary complications, especially ITBL, is needed to improve the outcomes for DCD grafts.

Liver grafts procured from donors after circulatory death have no increased risk of microthrombi formation.

Microthrombi formation provoked by warm ischemia and vascular stasis is thought to increase the risk of nonanastomotic strictures (NAS) in liver grafts obtained by donation after circulatory death (DCD). Therefore, potentially harmful intraoperative thrombolytic therapy has been suggested as a preventive strategy against NAS. Here, we investigated whether there is histological evidence of microthrombi formation during graft preservation or directly after reperfusion in DCD livers and the development of NAS. Liver biopsies collected at different time points during graft preservation and after reperfusion were triple‐stained with hematoxylin‐eosin (H & E), von Willebrand factor VIII (VWF), and Fibrin Lendrum (FL) to evaluate the presence of microthrombi. In a first series of 282 sections obtained from multiple liver segments of discarded DCD grafts, microthrombi were only present in 1%‐3% of the VWF stainings, without evidence of thrombus formation in paired H & E and FL stainings. Additionally, analysis of 132 sections obtained from matched, transplanted donation after brain death and DCD grafts showed no difference in microthrombi formation (11.3% versus 3.3% respectively; Pu2009=u20090.082), and no relation to the development of NAS (Pu2009=u20090.73). Furthermore, no microthrombi were present in perioperative biopsies in recipients who developed early hepatic artery thrombosis. Finally, the presence of microthrombi did not differ before or after additional flushing of the graft with preservation solution. In conclusion, the results of our study derogate from the hypothesis that DCD livers have an increased tendency to form microthrombi. It weakens the explanation that microthrombi formation is a main causal factor in the development of NAS in DCD and that recipients could benefit from intraoperative thrombolytic therapy to prevent NAS following liver transplantation. Liver Transplantation 22 1676–1687 2016 AASLD.

The outcome of primary liver transplantation from deceased donors in children with body weight ≤ 10 kg

Abstract:u2002 Between November 1982 and March 2006, 67 children with body weight ≤10u2003kg had a primary liver transplantation from deceased donors in our unit. The aim of this study was to analyze the outcome in terms of patient and graft survival and to search for factors affecting this outcome. Overall, one‐, three‐, five‐, and 10‐yr primary patient and graft survival rates were 73%, 71%, 66%, 63% and 59%, 56%, 53%, 48%, respectively. Twenty‐four of 67 (36%) children died and in the remaining 22 (33%), the first grafts failed and they were retransplanted. Cox regression analysis revealed that a need for retransplantation and urgent transplantation were important predictors for patient survival (pu2003=u20030.04 and pu2003=u20030.001, respectively). To assess whether the need for retransplantation can be influenced, all study variables were compared between surviving grafts and failed grafts. Cox regression analysis showed that only donor/recipient (D/R) weight ratio proved to be independent predictor for graft survival (pu2003=u20030.004). After comparison of graft survival with the long rank test according to different D/R weight ratios (3.0–7.0), the cut‐off point for significantly different graft survival approached 4.0. The one‐, three‐, five‐, and 10‐yr graft survival for technical variant grafts with a D/R weight ratio <4.0 was 85%, 68%, 68%, and 68% compared with a D/R weight ratio >4.0 was 44%, 38%, 38%, and 30%, respectively (pu2003=u20030.02). In summary, patient survival in children with body weight ≤10u2003kg is determined by urgent transplantation and the need for retransplantation. Graft loss and retransplantation in small children can be prevented by adequate size matching of donor and recipient whereby a D/R weight ratio <4.0 seems to offer the favorable outcome.

The impact of infections on delisting patients from the liver transplantation waiting list

Approximately 20% of the patients listed for liver transplantation die before transplantation can be accomplished. Understanding risk factors for waiting list mortality may help to improve survival and organ allocation. Infections are very common in patients with cirrhosis and are associated with significant morbidity and mortality. This study analysed the frequency and characteristics of infections in patients awaiting liver transplantation, identified risk factors for withdrawal from the waiting list and evaluated the impact of infections on the clinical outcome. A retrospective analysis of consecutive patients listed for liver transplantation in Rotterdam, the Netherlands from 2007 to 2014 was conducted. Infections occurred in 144 of 327 studied patients (44%). In this cohort, 23.4% of the patients on the liver transplantation waiting list were delisted or died before transplantation. Patients with an infection were 5.2 times more likely to become delisted than noninfected patients. In the 30 days after the first infection, patients were 33.8 times more likely to become delisted compared to noninfected patients. High age, high MELD score, refractory ascites and inappropriate antibiotic therapy were independent predictors for delisting due to infection. Infections occur frequently in patients on the liver transplantation waiting list. Emphasis on appropriate and timely antimicrobial therapy is required.