Vanguard Reports: highlights of the Joint Congress of ILTS, ELITA & LICAGE, Lisbon 2018, edited by Prashant Bhangui (click above or below...)
ILTS/LICAGE/ELITA Prague 24-27 May 2017: Congress commentaries by Deniz Balci and Christian Toso
Presentations reviewed by Deniz Balci:
State of the Art lecture: Liver inflammation and immunology: from basic science to liver transplantation
Speaker: Frank Tacke
- Dr Tacke, started with defining new concepts and roles of monocytes and macrophages which could be summarized as: impact homeostasis and inflammation, hepatocyte injury, hepatic stellate cell activation and angiogenesis.
- In liver, macrophage heterogeneity results with difficult immunological functions in disease progression as well as regression.
- Targeting macrophages could be via different methods namely microbubble, liposome or polymer in decreasing order of size of their respective particules.
- A proof-of-concept paper was published by Bartnect et al, showed decreased liver fibrosis using dexamethasone loaded liposomes. (Bartneck M, Warzecha KT, Tacke F. Therapeutic targeting of liver inflammation and fibrosis by nanomedicine. Hepatobiliary Surgery and Nutrition. 2014;3(6):364-376. doi:10.3978/j.issn.2304-3881.2014.11.02.)
- In another model of therapeutic targeting of monocytes in liver disease; LY6C high inflamatory macrophage becomes a fibrogenic macrophage that results with Hepatic stellate cell activation and extracellular matrix increase, while Ly6C low macrophage induces activated hepatic stellate cell apoptosis which may have a potential in reversal of fibrosis, showing potential benefit of therapeutic targeting of LY6C.
- The other cell line with various functions are Kupffer cells. Kupffer cell-mediated immunological tolerance to particulate antigens is abrogated in liver injury and fibrosis. They may assist in restoring antimicrobial surveillance in the early period after LT and promote tolerogenic actions in the long term.
- In liver transplantation, donor Kupffer cells may block activation before I/R injury occurs.
- Macrophages also take part in resolution of ischemia reperfusion injury in mice and man. There are various clinical implications.
- Monocyte-derived macrophages of the recipient are helpful in blocking infiltration after I/R injury
- After the transplantation, they could potentially be blocked to prevent graft fibrosis hence prevent disease recurrence.
- And, they may also counterbalance over-immunosuppression which may be helpful for HCC recurrence.
- Dr. Tacke concluded that, targeting monocyte/ macrophages can be therapeutic in liver diseases (e.g. CCR2/5 inhibitor in Nash fibrosis) which could be an interesting approach to novel interventions not only in chronic liver disease but also during and after liver transplantation.
Concurrent Oral Video Abstract Session:
Moderators: O Martin, KS Suh
Living Donor Liver Transplantation Using a Right Anterior Section of the Liver
Kyung-Suk Suh, Seoul, Republic of Korea
Dr Suh described a novel donor hepatectomy technique using right anterior section for the graft in LDLT for a recipient of 49-year-old male with BMI of 25. Donor volumetry was 0.57 for both the right posterior section and left hemiliver which were insufficient. The right anterior section was 710 ml with GRWR 0.96, with favorable portal and arterial anatomy hence selected as the graft. The total operation time was 292 minutes without transfusion and intra-operative complications. The middle hepatic vein of the right anterior section graft was anastomosed to the recipient's right hepatic vein and the rest were in standard fashion.
Dr. Suh concluded that despite being a complex donor operation with 2 parenchymal transection lines, this novel concept may expand the cadaveric donor pool and indication of LDLT.
A New Technique for Living Donor Liver Transplantation: Backtable Outflow Reconstruction and Bicaval Anastomosis with Veno-venous Bypass: Back to Basics
Deniz Balci, Ankara, Turkey
Dr Balci reported a new LDLT technique which simplifies outflow reconstruction and, at the same time aiming to increase safety for the recipient considered to be sensitive to hemodynamic instability due to systemic comorbidities.
The operation was divided into 3 steps: Hepatectomy without caval preservation and simultaneous veno-venous bypass (VVB) was set up using percutaneous femoral, internal jugular vein and portal vein cannulation. Back-table harvest of the recipient IVC from the diseased liver and new living donor graft outflow reconstruction. Finally, bi-caval anastomosis in the recipient before withdrawing VVB.
Dr Balci concluded that the technique may enable to simplify complex hepatic vein and caval anastomoses in LDLT using the VVB system under safe and hemodynamically stable conditions.
Pure Laparoscopic Living Donor Right Hepatectomy for Adult Liver Transplantation (4K, UHD)
Ki-Hun Kim, Seoul, Republic of Korea
Dr Kim presented a case of totally laparoscopic living donor right Hepatectomy. The donor was a 27 y.o woman with total liver volume of 1100 cm3 and right lobe was 630 cm3. Graft to recipient weight ratio was 0.82. The operation started with right hepatic artery and portal vein dissection. Parenchymal transection was completed using intermittent Pringle maneuver. The MHV was identified with intraoperative USG and tributaries from segments V and VIII were identified and divided. Finally, right bile duct was found and divided after performing intraoperative cholangiography with a mobile C-arm. The operation time was 300mins, and the estimated blood loss was less than 125ml. Graft weights were 610g Perioperative period was uneventful.
Dr. Kim suggested that the laparoscopic donor right hepatectomy is safe and feasible for liver transplantation, but should be performed in selected cases with a favorable anatomy in experienced centers .
Pure Right Lobe Donor Hepatectomy Using 3-D Laparoscopy for Adult-to-Adult Living Donor Liver Transplantation
Hye Ryeon Choi, Daegu, Republic of Korea
Laparoscopic-assisted Living Donor Right Hepatectomy
Adel Bozorgzadeh, Worcester, United States
Two more presentations were also reporting on a case of Laparoscopic Right Hepatectomy, Dr Choi from S.Korea presented pure laparoscopic right graft harvest using a Three-dimensional(3-D) imaging which they claim to enhance depth perception and facilitate operation. In Another presentation from the US by Dr Bozorgzadeh’s group, Hand-assisted laparoscopic right graft harvest technique was shown using a hand gelport placed on the right subcostal incision and three laparoscopic ports. The estimated blood loss was 500ml. The early postoperative course was uneventful for both the donor and recipient and they were discharged after 7 and 12 days, respectively. The authors concluded that hand-assisted laparoscopic living donor right hepatectomy is reproducible and can be safely performed.
Introduction of extrahepatic Glissonean approach for living donor hepatectomy
Taizo Hibi, Tokyo, Japan
Dr Hibi presented their extrahepatic Glissonean approach for living donor hepatectomy. The rational was to decrease bile duct injuries after living donor hepatectomy by both preserving blood supply of the hilar plate in the remnant liver by minimizing dissection and obtaining maximum margin of hilar structures for bile duct division. They defined 3 steps, Step 1. Isolation of the The right or the left Glissonean pedicle with an umbilical tape Step 2. Identification of hilar structures using Intraoperative cholangiography to find the point of bile duct division. Step 3 was Parenchymal division with modified liver hanging maneuver followed by division of hilar structures and graft retrieval. Dr Hibi concluded that extrahepatic Glissonean approach for living donor hepatectomy is safe and rational.
Laparoscopic Approach for Living Donor to Paediatric Liver Transplant
Javier Briceño, Cordoba, Spain
Dr Briceno reported their experience with 5 consecutive purely laparoscopic left lateral sectionectomy for adult-to-paediatric living liver donation, concluding that in specialized units, minimally invasive approach to living donor can be safely performed.
Patient Selection and Organ Recovery: Oral Abstracts
Moderators: John O’Grady and Jaroslav Chiupac
Increasing Liver Transplant Waitlist Dropout for Hepatocellular
Carcinoma with Widening Geographical Disparities: Implications for
Neil Mehta, San Francisco, United States
This study, based on UNOS data, suggests that the risk of drop-out for HCC patients has increased greatly in the US in the recent years, and especially so in long wait-time regions. This data promotes creating regions with more homogeneous waiting times throughout the country, or tailoring exception MELD points according to wait time.
Liver Transplantation for HCC Patients with High AFP Level – How to Select?
WC Dai, Pokfulam, Hong Kong
This retrospective study of 330 patients transplanted for HCC demonstrated that AFP (< vs. >400) can predict post-transplant overall and disease-free survival.
Outcome of Liver Transplant Recipients after the First Episode of Bacterial Infection
Alberto Ferrarese, Padua, Italy
Single-center retrospective cohort study of 114 patients experiencing a bacterial infection on the waiting list, and match to 762 patients without infection (using propensity). SBP was the most common infection. Infection is associated with an increased short-term risk of death. Once having recovered, patients with infection did not show an increased risk factor of death on multivariate analysis.
The Objective Liver Frailty Index Significantly Improves the Clinician “Eyeball Test” to Predict Mortality in Liver Transplant Candidates
Jennifer Lai, San Francisco, United States
The Liver Frailty Index (grip strength, chair standing strength, balance testing) helps predicting the risk of death on the waiting list independently of MELD. Compared to the subjective assessment by hepatologists (1 to 5), the risk of death on the waiting list was better predicted using the Frailty index in 529 patients (and even more so when combining both with a c-statistics of 0.74).
Association of Cardiac Structural Abnormalities to the Frail Phenotype in Liver Transplant Candidates: From the Functional Assessment in Liver
Transplantation (FrAILT) Study
Lorena Puchades, Valencia, Spain
Frailty index correlates with the cardiac structural and functional impairments on TTE (including left chamber measurement, ejection fraction) in a cohort of 374 patients.
Normothermic Regional Perfusion (NRP) Improves Outcomes after Liver Transplantation from cDCD Donors
Gabriel Oniscu, Edinburgh, United Kingdom
In Scotland, livers of DCD donors are not used as often as in other part of the country. In order to improve this issue, a team has been flying with a machine in 45 donors in order to perform regional perfusion (similar to ECMO). Comparing a subgroup of 14 patients with NRP and 45 standard DCD, NRP was associated with lower post-transplant ALT, no cholangiopathy (vs24% in the standard DCD group), no primary non-function (vs. 4 in the standard DCD group), and better graft survival (p<0.05). In the audience, a member from the Bilbao team confirms similarly good results at his institution.
Human Liver Transplantation after Normothermic Machine Perfusion (NMP), the First Report in the United States
Qiang Liu, Cleveland, United States
Phase 1 trial of liver graft NMP of 2 to 18 hours prior to transplantation, with perfusion of both the artery and the vein. After 10 transplantations, including 2 DCD, only one patient demonstrated early allograft dysfunction (one of the two transplants from DCD).
The Impact of Hypothermic Oxygenated Perfusion on Liver Viability Tested during Normothermic Machine Perfusion
Yuri Boteon, Birmingham, United Kingdom
Study of 10 discarded livers on HOPE (6 h) followed by NMP (2h, n=5) vs. on NMP (6h, n=5). HOPE effectively recharged cell energy, and increased the number of viable cells. The author suggests that both strategies could be combined in the future.
Repair on the Pump: Effective Delivery of Mesenchymal Stromal Cells (MSCs) to Liver Grafts during Isolated Machine Perfusion
Monique M.A. Verstegen, Rotterdam, Netherlands
The study infused GFP-expressing human MSCs into six pig livers on HOPE. The engraftment was similar with injection into the portal vein vs. the artery (yet a bit better through the artery). After one hour of HOPE, the engraftment appeared stable (as assessed by qPCR). Answering to a question, the author proposes to infuse donor MSCs into the liver graft prior to transplant.
ILTS Consensus Conference on Immunosuppression in Liver Transplantation
Park City, Utah February 7-8, 2017
A distinguished international faculty led by Michael Charlton and Josh Levitsky provided a state-of-the-art overview of current issues and progress in this field, soon to be summarized in an ILTS Consensus Statement and published in the official ILTS journal Transplantation.
Lectures and podcasts now available to ILTS members under Lectures...
ILTS 22nd Annual International Congress
Seoul, Korea May 5-7 2016
This was the largest multidisciplinary liver transplant meeting in Asia since 2010. It was attended by 1100 regional and international clinicians and scientists, representing all disciplines involved in the field. Over 600 abstracts were presented, along with 60 invited lectures and a live demonstration of laparoscopic right lobe donor hepatectomy. Its focus on innovation and safety in living liver donation was unprecedented.
Congratulations to congress co-chairs Professor S G Lee and Dr Michael Charlton on a superb program and another landmark ILTS meeting.
Ashish Singhal, Alessandro Vitale and Taizo Hibi report on ILTS Seoul highlights in Surgery
Thursday May 5, 2016
State-of-the-Art Lecture by Ashish Singhal
Professor CM Lo discussed reducing the risk for living donation through various mechanisms. LDLT activity varies considerably between western and eastern (20% vs 65-90%) parts of the world. In contrast to the west, LDLT has shown better or comparable results compared to DDLT. In Asia, LDLT has been successfully used in patients with FHF, high MELD score, early HCC and have shown clear survival benefit. Although there is variation in surgical risk to living donors between countries and centers, the main focus of LDLT has always been to minimize the donor risk through proper selection of donors (age, steatosis, FRLV), expertise of transplant surgeons, innovation, and mitigation.
Rising Star Symposium by Alessandro Vitale
The best classified studies of this congress have been presented by young invesitgators (<=42 yrs old) and their mentors. There were 3 basic science and 3 clinical studies.
Dr. Zhao presented on the key role of nuclear receptor farnesoid-X-receptor (FXR) axis in sustained regulating autophagy in liver ischemia-reperfusion, which provide a valuable clinical method to ameliorate liver ischemia reperfusion injury during liver transplantation. Dr. Li showed in an experimental model that IP10/CXCR3 signaling upregulated by liver graft injury directly induced the mobilization and intragraft recruitment of regulatory T cells, which further promoted HCC recurrence after transplantation. Dr. Ling presented on the role of donor graft microRNAs in the developmen of new-onset diabetes after transplantation.
Dr. Kalisvaart reported on the influence of donor warm ischemia time (DWIT ) in donation after circulatory death (n=70 cases) on development of acute kidney injury (AKI). In particular, he showed that not absolute DWIT, but length of donor agonal phase, has an important influence on development and severity of AKI. Dr. Rajanayagam presented on the role of autoantibodies (AuAbs) and immunoglobulins (Ig) in the etiology of chronic allograft hepatitis (CH) and fibrosis after pediatric liver transplantation.
Finally, Dr. Sapisochin reported the results of a multicenter retrospective study enrolling 48 patients with intra-hepatic cholangiocarcinoma (ICC) undergoing liver transplantation. Within this group, patients with very early ICC had a significantly better survival providing the rationale to design prospective studies on this field.
Surgical Techniques / Complications by Taizo Hibi
Various techniques utilized in living donor liver transplant (LDLT) was discussed. Dr. Yang presented 659 consecutive adult cases in which hepatic arterial reconstruction was performed by continuous suture with the parachute technique under surgical loupes. HAT was encountered in only 6 (0.9%) patients. Dr. Gopalakrishnan described the results of an RCT on placing a biliary stent (intraductal, transpapillary) vs. no stent for duct-to-duct anastomosis in LDLT. Bile leak was significantly higher in stented patients (45% vs. non-stented, 15%, p=0.01). On the contrary, an RCT comparing biliary stent (external drainage through the hilar plate) vs. no stent presented by Dr. Akamatsu revealed significantly increased incidence of biliary stricture at 5 years after LDLT in the non-stented patients (37% vs. stented, 19%, p=0.04). Dr. Soin presented the stepwise evolution of surgical techniques in 1245 consecutive cases since 2010. The incidence of hepatic vein thrombosis, biliary complications, etc. showed improvement over time and so was the 1-year survival rate. Dr. Jeng demonstrated excellent outcomes (2-month patency rate, 100%) of difficult venous outflow reconstruction (MHV tributaries, IRHVs, or both) using ePTFE vascular grafts in 262 cases. Dr. Kokudo compared the outcomes of right posterior sector vs. right liver grafts. They proposed that patients requiring separate arterial anastomosis (segments 6 and 7) or with supraportal right posterior are absolute contraindications for right posterior graft procurement. Dr. Lin presented outstanding results of microsurgical anastomosis of multiple biliary ducts in 964 cases with post-transplant biliary complications observed only in 8.5% of patients.
Featured Symposium # 4 - Surgical Techniques # 1: Cutting Edge of Minimal Invasive Living Donor Hepatectomy by Ashish Singhal
Dr You (Professor of Surgery,, The Catholic University of Korea, Seoul St. Mary's Hospital) presented his experience and data for feasibility of single port laparoscopic liver surgery in right donor hepatectomy between 2008-2015. From his experience, he concluded that single port laparoscopy assisted right hepatectomy is feasible for adult LDLT and minimizes donor incision- related morbidity. Dr Eguchi (Nagasaki University) presented his work on Hand Assisted Laparoscopic Donor Hepatectomy. Safety of living donor is of prime importance in LDLT. With this thought, their program has moved from right lobe living donor liver donation to left lobe program. For left lobe donation, they have used laparoscopy for dissecting the ligamentous attachments and for parenchymal transection used upper midline incision (HYBRID technique). They found that duration of surgery, blood loss, patient survival were not different between open and hybrid technique. Long term wound related complications were much less after upper midline incision. Dr Oliver Soubrane (Professor of Surgery, Beaujon Hospital) reported their experience and evolution of Totally Laparoscopic Donor Hepatectomy – Left Lateral & Left Liver, Right Liver at their center. In their experience, laparoscopic liver resection is not inferior to open resection. In 2002, the authors performed their first laparoscopic living donor hepatectomy. With this thought, they started with left lateral segmentectomy and finally reached to right hepatectomy. Complications rates are lower after laparoscopic liver donor hepatectomy compared to laparoscopic donor nephrectomy. There is huge difference between field of view between open and laparoscopic approach (anterior/posterior vs. caudal approach). Full laparoscopic donor hepatectomy resulted in faster recovery in donors, with short hospital stays and early return to work. This procedure has a steep learning curve. Dr Gary Levy (Professor of Medicine, University of Toronto) presented their experience and transition from open to Minimally Invasive Surgery at Toronto. Dr Ki-Hun Kim (Professor of Surgery, Asan Medical Center / Ulsan University) reported that pure laparoscopic living donor hepatectomy is feasible and safe in experienced centers. It requires an adequate experience in both LDLT and laparoscopic liver surgery. In experienced hands, pure laparoscopic right donor anterior sectorectomy is feasible.
Among all the presentations, it has been repeatedly stressed that safety of the living donor is of prime importance in LDLT.
ILTS Patient Selection / Organ Allocation / Organ Recovery Abstract Session by Alessandro Vitale
Dr. Vitale presented two studies on organ allocation for transplanting patients with hepatocellular carcinoma. In one monocentric study he reported on a strategy to spare organ donors based on the use of laparoscopic ablation followed by salvage liver transplantation in cases of tumor recurrence or liver failure. In the second study, he showed the external validation (in more than 80,000 US patients) of the HCC-MELD formula (based on 5-year transplant benefit calculation) as a potential strategy to establish allocation equity for patients with and without HCC in a common waiting list.
Dr. Narasimhan reported a very important project on developing a deceased organ donor network in the state of Tamilnadu, India and reproduced in other states of the country. Dr. Selzner presented on the first successful clinical Normothermic Ex Vivo Liver Perfusion (NEVLP) experience with Steen solution, a human-based albumin-based perfusate. Dr Pomfret compared the results of liver transplantation with “imported grafts” to locally procured livers in a single Centre in USA showing similar outcome after an appropriate donor-recipient matching policy. Dr. Bortacen presented an interesting study on the great discrepancy between true costs and reimbursements for high MELD patients in a single US centre suggesting a broader sharing in the US to equalize costs with regions transplanting patients with lower MELD score. Dr. Rammohan reported on interventions to prevent small for size dysfunction (SFSD) after living donor liver transplantation in a single Indian centre. Interventions to modulate post-reperfusion portal pressure and other technical skills may decrease SFSD rates and SFSD related mortality. Finally, Dr. Ershoff showed the first study to examine the effect of left atrial volume index as a predictor of post liver transplant mortality using a multivariable model.
Friday May 6, 2016
Featured Symposium #6-HCC#1-Hot Debate in LT for HCC by Taizo Hibi
The first topic was the selection criteria for HCC. Dr. Lake showed the excellent results of UCSF downstaging protocol and used them as an example to claim that size and number remain to be the gold standard for patient selection because they are easy to assess without using invasive measures. On the other hand, Dr. Man underscored that "Biology is king" through an extensive literature review. A wide variety of biological markers such as AFP, Capn4, miRNA-155, CXCL5, HOTAIR, GPx3 were demonstrated to be independent predictor of tumor recurrence, with some of them being therapeutic targets of treatment as well. At the end of the discussion, most of the audience agreed that a combination of morphological criteria and biomarkers is needed to further refine selection criteria.
The second topic was resection vs. liver transplantation upfront for patients with HCC within Milan criteria. Dr. Clavien depicted recent advancements in the surgical treatment of HCC (laparoscopic resection and ALPPS) and stated that limits for resection should be pushed further. He concluded that by deliberate patient selection, the outcomes of resection-first approach followed by either bridge or salvage LT should provide comparable results to primary LT. Meanwhile, Dr. Adam showed that resection provides similar overall survival with LT only for single HCC <3 cm with lower disease-free survival. He emphasized that the transplantability rate after initial resection is much lower in clinical practice than theoretically expected and that salvage LT will put patients at risk for losing the opportunity for cure (as high as >50% of patients). Finally, the majority of the audience were up to primary LT for resectable HCC within Milan criteria.
Featured Symposium # 8 - Pediatrics by Ashish Singhal
Dr Taner (Assistant Professor of Surgery, Mayo Clinic Rochester) reported strategies for Combined Liver-Kidney Transplantation in Hyperoxaluria. Primary Hyperoxaluria is a rare genetic disease with heterogeneous phenotypic presentation. Mostly diagnosed during childhood, and most of them presented with nephrocalcinosis and/or urolithiasis. Combined liver-kidney transplant provides the best outcomes. Simultaneous liver-kidney transplant provides additional immunological benefits to the kidney allograft, if grafts are received from the same donor. Dr Egawa (Professor of Surgery, Tokyo Women's Medical University) reported the effect of rituximab on ABO Incompatible Pediatric Liver Transplantation (Japanese Multicenter Study). There has been increase in ABOi LT in Japan, but results demonstrated an acute drop in survival within 3 months. The incidence of AMR was approximately 10% with other complications including hepatic necrosis and intrahepatic biliary complications. Dr Jean De Ville de Goyet (Professor of Pediatric Surgery, Bambino Gesù Childrens Hospital, Italy) presented the technical management of the attenuated portal vein. Hypoplastic PV is defined as PV < 5mm in size. Patients with biliary atresia often have hypoplastic PV. Other conditions include polysplenia syndrome, abernathy malformation, etc. Hypoplastic PV leads to potential problems: low flow reperfusion, graft dysfunction, early thrombosis, graft loss, death, late thrombosis, and chronic portal hypertension. Possible technical solutions are: interposition graft, lateral portal venoplasty. In their series of 139 pediatric LTs (2008-2015), 14 patients develop portal vein thromboses (early 8, late 6). Twelve of these 14 patients were of biliary atresia. Dr Chen (Professor of Surgery, Chang Gung Mem Hospital, Taiwan) presented various surgical techniques and their modifications to prevent and manage vascular complications in pediatric LDLT. Dr Mazariegos (Chief, Pediatric Transplantation Children's Hospital of Pittsburgh of UPMC) presented data on extending donor limits in pediatric OLT. The balance between ideal allografts and donor limitations such as donor age, steatosis (pediatric vs. adult), hypernatremia, and DCD was emphasized. The main objectives are rapid recovery of the graft, avoidance of warm ischemia, minimization of cold ischemia time, and rapid reperfusion. Donor characteristics for “split-able” liver at UPMC are: donor age < 40 years, single vasopressor, serum transaminases < 3 X upper limit of normal, and BMI < 28. Ultimately, decision making in graft selection depends on the degree of portal hypertension, patient acuity, and graft volume in context with donor availability and risk factors.
Featured Symposium # 11 - Transplantation in Future: Novel Technology to Substitute Human Liver by Ashish Singhal
Dr Ekser (Assistant Professor of Surgery Transplant Division, Department of Surgery, Indiana University School of Medicine) presented ‘Clinical Xenotransplantation: Will Dream Come True?’ He defined and reported the history of xenotransplantation (Starzl/Hardy/Barnard) including transplant of kidney/heart from baboon/pigs. Per immunological clock, gorilla is very close to human being. But we continue to use pig organs in xenotransplantation despite the fact that pigs are immunologically very different than human beings. Advances in genetic engineering (single knock-out, double knock out, zinc finger nuclease, CRISPR/CAS9 system) have played a major role in accomplishing this. Recent literature and media suggest that clinical xenotransplantation is the next medical revolution. Dr Strom (Professor, Cell Transplantation and Regenerative Medicine Karolinska Institute) reported the current status of hepatocyte transplantation. Hepatocyte transplantation is an upcoming field of regenerative medicine and may help in bridging patients to “whole” organ transplantation. Hepatocyte transplantation may allow repopulation of liver in patients with ALF and correction of metabolic effects without whole organ transplantation. This requires a donor liver for isolation. He discussed two techniques: Pittsburgh (Radiation) and Karolinska (surgical resection). He described the problems encountered with hepatocyte transplantation including engraftment, viability, and assessment of donor cell function. Finally, he reported the upcoming role of human amnion epithelial cells. Dr Nyberg (Professor of Surgery and Biomedical Engineering Mayo Clinic Rochester Minnesota) reported the recent advances in Artificial and Bio-artificial Liver Support System. First, he discussed the economics, role, and type of current liver support devices (artificial vs bioartificial). Recent Phase 3 trial of study using ELAD showed no benefit in patients > 50 yrs and/or with high MELD score. In another, another study (RALF study) has showed improved outcome with SRBAL. He was optimistic of the advancement and utilization in clinical practice over the next 5 years.
Concurrent Oral Abstract Sessions Extended Criteria Donor / Disease Transmission by Taizo Hibi
In this session, DCD grafts, elderly donors, and monitoring of Chagas disease were discussed. Dr. Chen demonstrated that DCD donor age >60 years were associated with similar graft and survival rates and biliary complication rates with <60 years despite having an increased incidence of initial poor function and CNI toxicity. Dr. Khorsandi developed a DCD risk stratification index (DCD-RI) by combining liver etiology, MELD score, retransplant, WIT, CIT, donor hepatectomy time, and donor team. DCD-RI score independently predicted graft loss and graft survival. Dr. Ghinolfi performed a paired-match analysis between donor age groups 18-69 and >=70. The use of elderly donors was not associated with an increased risk of arterial and biliary complications. While donor age was an independent predictor of decreased survival in HCV+ patients, donor anoxia and history of diabetes were poor prognostic factors in HCV- patients. Dr. Balderramo described the routine use of quantitative PCR for early detection of Trypanosoma cruzi (T. cruzi), the parasite causing Chagas disease, after LT. Eight/106 (7.5%) high-risk patients for Chagas disease were identified prior to LT. Of these, early replication of T. cruzi was observed in 3 seropositive recipients. All underwent anti parasitic therapy, which resulted in rapid decrease in parasite load, and none died of CD. Dr. Paugam demonstrated in a prospective study that donor's alpha-glutathione S-transferase level significantly correlated with the occurrence of primary non-function (4% of 54 LT recipients for cirrhosis) but not with early allograft dysfunction. Dr. Scalera conducted a retrospective analysis comparing the intraoperative hemodynamic profile between 30 recipients each for DBD and DCD grafts. The post reperfusion syndrome rates were similar between groups and recipients of DCD grafts showed higher mean arterial pressure after hepatic arterial anastomosis and better pH at the end of transplant, implying that the recipient selection criteria for DCD grafts can be carefully expanded.
Plenary Abstract Session by Alessandro Vitale
Dr. Teperman presented the results of a RCT comparing extracorporeal therapy of alcoholic hepatitis (AH) with C3A cell therapy versus standard of care. This trial showed a significant survival benefit in a subgroup of patients (MELD <28, age<47 years, preserved renal function, not severe coagulopathy). Dr. Charlton presented the results of a RCT evaluating the efficacy and safety of sofosbuvir/velpatasvir for the treatment of HCV patients with decompensated liver disease (ASTRAL-4 study). The association of SOF/VEL+RBV for 12-weeks resulted in high SVR rates across all HCV genotypes in decompensated patients with early improvements in liver function. In the third RCT, Dr. Duvoux reported the results of the SIMCER study comparing withdrawal of tacrolimus combined with Everolimus and EC-MPS vs standard treatment in de novo Liver Transplant recipients. They found a significant benefit in terms of renal function in the study group, with efficacy of immunosuppression comparable to the standard treatment despite a higher incidence of SAEs.
Dr. Krishnasamy presented a new interesting molecular mechanism (epigenetic regulation of mitochondrial function by a lysine specific demethylase-1) able to inhibit oxidative stress and prevent mitochondrial dysfunction during hepatic ischemia reperfusion. Dr. Coffey reported an international multicentre experience enrolling 250 controlled cardiac death donors and he showed that functional warm ischemia did not predict early post transplant outcome. Dr. Kawamura presented the Sapporo-Japan experience of LDLT using small for size grafts (GV/SV less than 35%) and their strategies to optimize post transplant outcome (donor recipient matching, portal flow modulation, early enteral feeding, and prevention of rejection with higher immunosuppression,). Dr. Narayanan presented a retrospective study in Mayo Clinic Rochester showing that recurrent or de novo allograft steatosis predicts cardiovascular events but not survival post-liver transplant. Finally, Dr. Gyoeri described an analysis of the Eurotransplant Registry on the impact of delta MELD on post transplant outcome.
ILTS Malignancies Abstract Session by Alessandro Vitale
Dr. Zanetto presented the impact of circulating microparticles on the risk of portal vein thrombosis in patients with liver cirrhosis and hepatocellular carcinoma. Dr. Aravinthan discussed the intention-to-treat outcome of HCC patients within the Extended-Toronto criteria but beyond the UCSF criteria listed for liver transplantation. The main predictors of survival in this study were response to bridging therapy and AFP<400 ng/ml. Dr. Costentin reported on the external validation (Italian 4 centers database) of two scores predicting post transplant risk of HCC recurrence. Dr. Mathur presented an interesting study showing that visceral obesity is associated, in patients within Milan criteria, with poorer tumor grade on explant pathology and an increased recurrence following transplantation. Moreover, he showed that this effect is mechanistically caused by elevated pro-tumorgenic leptin and attenuated adiponectin production in obesity. Dr. Kim presented a translational study showing that high-concentration of Nuceloside Analogue induced apoptosis of HBV-expressing liver tumor cells. Dr. Hwang reported on a study about clinical features of late HCC recurrences after liver transplantation. Dr. Yang analyzed the outcome of 266 HBV-associated HCC patients undergoing LT and proposed a new score based on neutrophil and platelet-to-lymphocyte ratios plus alpha-fetoprotein values to predict post transplant outcome. Dr. Wang presented a pilot safety study of allogeneic natural killer cells used as adoptive immunotherapy to treat the recurrence of hepatocellular carcinoma after liver transplantation. Finally, Dr. Akamatsu reported on a Japanese nation-wide survey focusing on de novo malignancies after living-donor-liver transplantation. He found that the profile of de novo malignancies in Japanese recipients, in which leukemia and tumors in central nervous system are leading in SIR, was different from that of Western countries.
ILTS Malignancies Video Session by Alessandro Vitale
Several surgeons presented interesting videos on surgical techniques. These include:
1. Living Donor Related re-transplantation with resection of stenotic vena cava with stent and removal of the stent. Vena cava was reconstructed directly to the cardiac right atrium creating a new triangle orifice for anastomosis with the graft.
2. Auxiliary orthotopic liver transplantation in a 2 years old girl with acute liver failure.
3. Anterior hepatic parenchymal transection for Isolated Caudate Lobectomy
4. Living Donor Left Lateral Segment Liver Transplant in pediatric patients with a particular focus on Portal Vein Anastomosis Technique
5. Anterior approach right hepatemtomy combined with Inferior Vena Cava Thrombectomy using Transdiaphragmatic Intrapericardium IVC Occlusion
6. Successful Living Donor Domino Liver Transplantation for Biliary Artresia from a Maple Syrup Urine Disease Patient
7. Pure Laparoscopic Extended Right Hemihepatectomy in a Living Donor
8. Pure 3D Laparoscopic Right Hemihepatectomy in a Living Donor
9. Various Types of Donor Incision in Living Donor Liver Transplantation
Saturday May 7, 2016
Featured Symposium #15: HCC #2-Update in LT for HCC by Taizo Hibi
Dr. Suh introduced previous attempts to expand the Milan criteria and the results of a recent multicenter, prospective trial in Korea. In this study, LT for far advanced HCC (>10 nodules, >10 cm, major vessel invasion; n=169) provided acceptable 5-year overall survival (OS) of 53% if the AFP+DCP level was <300. If the level was >300, the recipients were associated with a dismal prognosis (5-year OS, 11%). He also showed the no-touch isolation technique at the time of total hepatectomy by clamping supra and infra hepatic IVC before the mobilization of the right liver.
Dr. Lerut presented an extensive literature review on the importance of patient selection based on tumor size and number (morphology), static and dynamic tumor markers (AFP and DCP), mRECIST criteria, inflammatory biomarkers (neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio), and waiting time. He also described a novel "TRAIN" score (Ann Surg, in press), a combination of mRECIST criteria after locoregional treatment, AFP slope, NLR, and waiting time. TRAIN score was predictive of patient death and tumor recurrence depending on the waiting time.
Dr. Roberts showed the results of downstaging protocol in UCSF, Bologna, and U.S. multicenter trial and discussed the rationale for patient eligibility and exclusion criteria. The long-term outcomes of patients who were successfully downstaged (60%-70% of patients) were comparable to those within the Milan criteria. He proposed inclusion criteria for downstaging of HCC (single lesion <= 8 cm or 2-3 lesions each <= 5 cm with sum diameter <= 8 cm as upper limits of tumor burden) and exclusion criteria for LT (progression of tumors, major vessel invasion, lymph node metastasis, extrahepatic disease, infiltrative tumor growth, and high AFP levels).
Dr. Berenguer presented an in-depth review on immunosuppression and HCC. High CNI exposure revealed to be an independent risk factor of HCC recurrence. Single center studies, registry analysis, a metaanalysis, and a systematic review showed that the use of mTOR inhibitor was associated with lower HCC recurrence rate. There is only 1 prospective, randomized trial that looked at the impact of mTOR inhibitor (sirolimus) use from 4-6 weeks after LT on HCC recurrence. Although there was no significant difference in recurrence-free survival (RFS) and overall survival (OS) between the sirolimus and no-sirolimus groups, there was an RFS and OS benefit in the first 3-5 years in low-risk patients. At the moment, avoidance of high CNI exposure is recommended but whether antineoplastic immunosuppression is worthwhile warrants further investigation.
ILTS International Directory of Liver Transplant Centers
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Mastering Viral Infections in Liver Transplantation: Clinical case presentation: “De novo autoimmune hepatitis recurrence after IFN-free antiviral therapy for hepatitis C after liver transplantation”
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