ILTS 16th Annual International Congress, Hong Kong
Full program details
ILTS Congress Daily Report: Olaf Guckelberger reports on the very successful recent meeting in Hong Kong. See also Josh Levitsky's reports in the Hepatology Section.
Saturday, June 19
Farewell
The final day of the congress started with a plenary session. SungGyu Lee from Seoul gave kind of an introductory lecture summarizing the development of living donor liver transplantation in his institution. They now perform more than 300 liver transplants per year and regard remnant liver volumes of 30 % as acceptably safe in donors without fatty changes of the liver. Thereafter, René Adam from Paris reported morbidity and mortality data of the European Liver Transplant Registry overseeing more than 3000 living liver donors. Overall the donor mortality equals 0.2 %. With increasing experience the rates of major (i. e. death) and minor complications decreased after the year 2000 compared to earlier time periods. The rate of intermediate complications (Clavien Grade III-IV), however, did not decrease over time.
The following presentations related to aspects of the recipient's surgery. After more than 400 LDLT, Balachandran Palat from New Delhi concluded that with proper inflow modification and venous outflow reconstruction the threshold of the GRWR can safely be lowered to 0.7, maybe even 0.6 in the perfect donor. Tsan-Shiun Lin et al. from Taiwan presented their experience with microsurgical biliary reconstruction in LDLT (i. e. use of microscope and 6/0 sutures). The overall complication rate was 9.2 % (2.8 % strictures, 6.4 % leaks), with significant improvements in the most recent series.
Results from the Italian Liver-Match Observational Study presented by Mario Angelico caution the use of HBcAb positive donor organs. The one year graft survival rates in HBcAb positive grafts and negative controls were 72 % and 83%, respectively. No graft loss occurred due to HBV infection. In a multivariate analysis only donor age (or donor risk index) and HBcAb positivity were identified as independent variables.
The final block of presentations in this session related to results in LT for viral hepatitis. Michael Charlton reported data from the PHOENIX trial comparing a prophylactic PEG/RBV regimen early after LT with the established observational strategy. The prophylactic treatment, however, demonstrated no beneficial effect. Also, due to the safety profile of this treatment nearly half of the screened patients had to be excluded and many patients discontinued the trial. Greg McKenna from Dallas reported on 16 patients with HCV that have been converted to sirolimus one year after LT. The progression of fibrosis at year two has been compared to HCV patients that never received SRL. While the SRL group demonstrated a fibrosis stage regression (-0.19), the control group presented a progression by 0.54 (p=0.04). Dennis Eurich from Berlin demonstrated that genetic variations of IL-28b have an impact on graft inflammation responses in HCV positive liver transplant recipients.
The closing session I attended was a featured symposium entitled Protecting the Donor. First Yukihiro Inomata from Kumamoto, Japan, presented an overview of strategies to assess and evaluate the living donor.
Elizabeth Pomfret from Burlington, USA, gave an update on donor mortality and morbidity based on a survey mailed to many transplant centers. The overall complication rate has been reported with 38 %, including 26 catastrophic events (21 deaths, 4 LT, 1 vegetative state). Also she urgently requested to report “near miss” events like the need for redo surgery or liver transplantation, significant hemorrhage, portal vein thrombosis or injuries to the donor vasculature.
See Ching Chan from Hong Kong emphasized that the donor's Quality of Life after donation is at high risk when the recipient demonstrates a risky behavior after transplantation or the donor suffers a psychiatric condition. An elaborate assessment is mandatory.
Kyung-Suk Suh from Seoul addressed the role for a laparoscopic donor hepatectomy. In his view it's a safe and beneficial procedure that, however, should rather be named “minimal incisional”.
Gary Levy's lecture on ethical controversies in living donation closed the session. For one he emphasized that anonymous donation redresses a significant problem in living donation. Recipients without a suitable living related donor are considerably disadvantaged. With respect to organ vendors, although it's banned in most countries, there are already many incentives in place (i. e. lifelong health insurance for living donors, burial cost coverage in deceased donors). Inevitably, a regulated reimbursement policy will be implemented.
Today's surgical summary:
We enjoyed a great congress in Hong Kong!
Many thanks and congratulations to the organizers!
Olaf Guckelberger.
Friday, June 18
Different Views
Following the Website Committee Meeting, the featured symposium “Around the World in 90 Minutes” caught my attention.
First Abhi Humar from Minneapolis reported the North American view on split liver transplantation for two adults. He specifically addressed issues with the current allocation system. Despite being successful in general, complications such as small-for-size syndrome are provoked.
Juan Carlos Valdecassas took the European standpoint and provided data regarding DCD donors. He emphasized the high incidence of biliary complications. However, clinical studies with category 2 DCD donors (i. e. unsuccessful resuscitation, uncontrolled) are underway [Comment: In some European countries DCD donors are banned. O.G.].
ABO-incompatible living donor liver transplantation has been addressed by Hiroto Egawa from Japan. He reported good results with pre-transplant plasmapheresis, rituximab administration, simultaneous splenectomy and post-transplant hepatic artery infusion therapy. However, protocols still have to be adopted.
Shin Hwang from Korea presented innovations in selecting living donors to facilitate liver transplantation when no suitable living related donor will be available and deceased donors are not an option. ABO-incompatible transplantation has been mentioned earlier, but also concepts like Good Samaritan donors, dual graft liver transplantation and organ exchange between couples have been applied with good success.
Finally, Joao Seda Neta from Brazil presented the Modified-PELD scoring system. To compete with adult recipients for liver grafts under the MELD allocation system, the PELD score will be multiplied by 3. Thus, the number of split liver transplants will increase and scarce donor organs will be better utilized.
The concurrent session on Radiology also provided interesting views. Three abstracts dealt with radiological interventions to treat surgical complication. Hsin-You Ou from Taiwan covered the rare event of portal venous stenosis. In the presence of clinical portal hypertension and a confirmed occlusion or stenosis above 50%, a trans-hepatic, trans-splenic or surgical guided portal stent placement has been performed. Depending on the time course, the technical success rate equaled 69% only. Therefore the authors cautioned an early diagnosis and early treatment. During a mean follow-up of 12 months the patency rate equaled 91%. Fatih Boyvant from Turkey reported the Ankara experience with the placement of arterial covered stent grafts in cases of hepatic artery complications. Endovascular procedures were performed as early as 8 days following LT and a technical success has been achieved in 94%. The primary and secondary patency rates were 73% and 85%, respectively. Mohamed Shaker from Cairo reported on 19 patients with biliary strictures after LDLT that were treated with percutaneous dilatation and stenting. A clinical success occurred in all but one patient (94%). Although still preliminary, he argued for replacing ERC in post-LDLT biliary strictures. All procedures were performed under general anesthesia, but subsequent interventions may easily be performed endoscopically.
Three more abstracts addressed imaging modalities to select live donors. Kyoung Won Kim from Korea presented an automated blood-free CT volumetry to estimate the weight of the right hepatic lobe. The mean deviation from the actual graft weight equaled 5% with the new algorithm, while the conventional estimate differed by pproximately 11%. Hsien-Wen Hsu et al. from Taiwan compared their magnetic resonance cholangiography imaging of the biliary tree with findings from intraoperative cholangiography. MRC achieved an accuracy of 91%. In the mismatch group, no transplantation had to be abandoned and no switch of graft was required. Finally, Andrea Schenk from Germany presented a new sequence for Gd-EOB-DTPA-enhanced MR imaging and 3D reconstruction. A promising glimpse into the future.
Another concurrent session covered Surgical Techniques/Complications. Again two abstracts addressed arterial complications. Nam-Joon Yi from Seoul favored an aggressive surgical intervention strategy in early hepatic artery thrombosis (< 2 months). Due to a tight ultrasound protocol, 65% of all detected HAT were without overt symptoms. Surgical revascularization has been achieved in all patients. David Boulate from France again presented results from transluminal interventions for HAT. Diagnosis had been achieved at a mean follow-up of 80 days after LT. A technical failure occurred in 4.5% (n=1), a residual stenosis also had been observed in one patient. Therefore, the success rate accounted for 91% and after a median follow-up of 24 months 76% of all patients are asymptomatic.
Biliary complications were addressed by Siu Ho Kenneth Chok from Hong Kong. The authors reviewed 265 right lobe LDLT. The biliary stricture rate equaled 20% in duct-to-duct as well as biliodigestive anastomoses. In a multivariate analysis cold ischemic time (HR 1.012) and acute rejection episodes (HR 3.08) had been identified as independent risk factors. The authors cautioned, however, possible biases in this retrospective study. Due to their abnormal liver tests, patients with a biliary stricture had more biopsies. Prolonged CIT may reflect surgical difficulties.
Tanveer Singh et al. from New Delhi reported on their center's results with the utilization of cryopreserved veins from explanted livers for portal or venous reconstruction in LDLT. In total, 42 of such grafts have been used with a 100% patency rate at 3 months. During a median follow-up of 17 months no overt complications occurred.
Finally, Ernest Hidalgo from Edinburgh, UK, presented a preliminary series of patients with spontaneous splenorenal shunts. To achieve a portal vein flow of at least 1200 ml/min., ligation of the right renal vein has been performed at the time of cadaveric LT (n=3) or in a subsequent procedure (n=2). So far no complications have been observed.
Today's surgical summary:
Keep your vision clear. There are rising stars around.
Olaf Guckelberger.
Thursday, June 17
Rising Stars
The day kicked off with the Vanguard Grand Rounds Case Presentations. Constantino Fondevila from Barcelona presented an 51 years old patient with hepatitis C induced liver cirrhosis, who achieved a sustained viral response after combined antiviral treatment. During follow up, two small HCC nodules have been detected and successfully treated with minimally invasive resection. Recurrence of HCC has been demonstrated after four months and the patient has been listed for liver transplantation. Nine months after resection liver transplantation has been performed. The specimen demonstrated multifocal HCC with numerous small lesions that have not been detected on CT scans. The educational objectives were: 1) Despite viral clearance, the continued risk for HCC requires close surveillance, 2) Bridging therapies for transplantation are discussed controversially and relate to the different allocation systems, 3) Multiple tumors in the initial findings indicate a high recurrence rate after treatment. Kyung-Suk Suh from Seoul lead the senior discussion and raised questions about the oncological view of laparoscopic resections for HCC (anatomic resection?, tumor spread?, need for transfusions?) as well as transplantation related questions (less adhesions?, staging?, biological selection?). The actively participating audience emphasized that TACE may be a beneficial bridging therapy in allocation systems with waiting times above six months. More educational cases have been discussed lively, but unfortunately can't be addressed in this short summary.
The Rising Star session, kindly supported by Novartis, made the day. First, Anil Dhawan from London mentioned the importance of extrahepatic threats, such as decreased renal function, to longevity after liver transplantation. With the notion that creatinine sometimes misinterprets GFR but other biomarkers could replace Cr-EDTA GFR in the future, he introduced his Young Investigator Prashant Bachina. His research demonstrated that Cystatin C serum concentrations significantly correlated with the measured GFR in post-transplant patients, with a level above 1.04 mg/l matching a GFR below 80 ml/min/1.73 m2. Furthermore, the cost of the Cystatin C assay equaled US$ 5, while determination of the Cr-EDTA GFR adds up to US$ 294.
Next, Jerzy Kupiec-Weglinkshi from Los Angeles introduced the role of CD4+-T-cells in ischemia-reperfusion induced liver damage as well as his Young Investigator Haofeng Ji. In a model of murine warm hepatic IRI, he studied the impact of PD-1/B7-H1 activated T-cells on the hepatic injury. Mice treated with B7-H1Ig were protected against hepatic IRI as demonstrated in decreased serum ALT levels, decreased neutrophil infiltration and reduced positive TUNEL staining. Treatment with anti-IL-10, however, fully “restored” the ischemia induced liver damage.
Kwan Man from Hong Kong presented the concept of Epithelial-Mesenchymal Transition (EMT) of biliary epithelial cells as a factor for post-transplant graft fibrosis. In a rat model of fatty small-for-size liver grafts, her Young Investigator XB Lui demonstrated an increased Aldose Reductase expression as well as oval cell activation, which has been significantly reduced in AR-knockouts. Also Notch2 and TGF-b1 expression has been increased and co-localization experiments refered to ductular cells.
According to Michael Heneghan from London, no aetiology for Budd Chiari Syndrome can be identified in 25% of all patients at the time of diagnosis. However, 80% of patients with a JAK2 mutation develop a myeloproliferative disorder during follow-up. His Young Investigator Rachel Westbrook took the task to evaluate the impact of this mutation on outcomes after liver transplantation. 61% of their BC patients demonstrated a JAK2 mutation and were associated with a significantly higher rate of post-LT thrombotic complications. Other conditions such as a TET2 mutation or a 46/1 haplotype had no impact on outcome measures.
Tor Tonnessen from Oslo introduced the concept of microdialysis to monitor metabolic parameters. Ischemic conditions may be identified by increased lactate measurements while pyruvate concentrations decrease. A hypermetabolic state, however, will demonstrate both increased lactate and pyruvate. His Young Investigator Haakon Haugaa performed microdialysis in 73 liver transplantations for a median of 9 days. Measurements had to be abandoned at that time due to catheter related problems in the majority of cases. In patients with proven ischemic complications, the lactate/pyruvate ratio doubled, while rejection episodes demonstrated an increase in both parameters with almost no change of their ratio.
Finally, Douglas Hanto from Boston demonstrated that inhaled CO protects livers of IRI in small animals. To identify the impact on liver regeneration has been the task of his Young Investigator Kaori Kuramitsu. In a murine model of 70% partial hepatectomy, mice were placed in a CO-chamber for one hour prior to surgery. Compared to controls the postoperative weight gain as a measure of overall health improved, Ki-67 positive cells were higher at 24 hours, liver function tests improved and the HGF peak expression demonstrated a time-shift to 12 hrs as compared to 24 hrs in controls.
The concurrent session on Outcomes bundled a number of interesting presentations. Unfortunately, I can highlight only a few. Two abstracts referred to the donor age as risk factor, although in different settings. Avolio et al. from Italy reported a multicenter study on D-MELD (donor age x labMELD) as a predictor for graft survival after LT. The 90th-percentile cut-off equaled 1538 for all patients, while HBV or HCV patients demonstrated cut-off points of 722 and 548, respectively. This means, a non-HBV, non-HCV patient at a MELD score of 28 can safely receive a donor organ up to 55 years, while at a MELD of 35 the safe donor age decreases to 44 years. You do the math for HBV and HCV patients. Kawachi et al. from Tokyo determined the impact of donor age on graft regeneration in LDLT. Older donor organs (> 50 years) demonstrated increased transaminases early after transplantation and decreased survival figures. Which has been more pronounced in the small-for-size subgroup with no survivor beyond three years.
Also from Italy derived a multicenter, case control study on the 10 year results of adult split liver transplantation, presented by Marco Spada. 144 SLT were performed utilizing 138 right lobes, 2 left lobes and 4 left lateral sections. In multivariate analysis, only the UNOS status, but not the use of extended right lobes, has been identified an independent risk factor for mortality.
Analysing UNOS data, Kayo Waki et al. determined the outcome of LT patients coinfected with HBV and HCV. Interestingly, they demonstrated that 10 year survival figures in patients with HBV/HCV did not differ from results in HCV/HBV-negative or HBV-positive/HCV-negative patients (54%, 57%, 63%). The worst outcome demonstrated patients with HCV infection only (46%, p<0.001).
Further abstracts demonstrated successful desensitization of T lymphocytes in cross-match positive adult LDLT or surgical opportunities in pre-transplant portal vein thrombosis.
Another concurrent session engaged with the Living Donor. Two abstracts presented results from laparoscopic donor left lateral sectionectomy. Ki Hun Kim presented data from Seoul comparing open with laparoscopic procedures. Postoperative AST levels were lower in the laparoscopic group (190 vs. 460 U/l, p=0.002) and the postoperative stay has also been reduced (7 vs. 10 days, p<0.001). Operating time, blood loss or costs did not differ in both groups. Fabien Stenard summarized experiences from France with the laparoscopic approach. Out of 53 procedures they reported 4 conversions to open surgery (BMI > 29 in 2, bleeding in 2) and 2 biliary leaks, that both had successfully been treated with redo laparoscopy.
Two more abstracts related to portal inflow modulation in LDLT. Mauricio Barriga et al. clarified that high portal flow is not the same as high portal pressure and decisions on inflow modulation should be based on both. 1/3 of patients with a high portal pressure demonstrated only a low portal flow. Accordingly, Masahiko Taniguchi form Sapporo reported that in their center a PVP above 20 mmHg or a PVF above 300ml/100g/min mandates measures for inflow modulation. In this setting, outcomes do not differ between groups requiring inflow modulation or not.
Kyung-Suk Suh from Seoul reported their results with the utilization of PTFE-grafts for venous drainage in right lobe LDLT in 129 patients. The 1 months and 2 years patency rates equaled 94 and 61%, respectively, with a complication rate below 1%.
The final presentation was given by Elizabeth Pomfret from Burlington, reporting Quality of Life data from live liver donors. In general, they exhibit mental and physical health scores above average, but donors with lower regenerated liver volumes also display reduced physical SF-36 scores.
Remember: It's all about the donor!
Olaf Guckelberger.
Wednesday, June 16
The Art of Medicine and Surgery in Liver Transplantation: Today and Tomorrow ... was the title of the Astellas sponsored satellite symposium that traditionally precedes the Annual Congress of the ILTS. There were two surgical sessions that opened and closed this symposium.
First Ronald Busuttil from Los Angeles reported long-term outcomes in survivors of liver transplantation beyond 20 years. Remarkably, the survival rate exceeded 50% of patients and Quality-of-Life measures demonstrated superior results compared to patients with chronic conditions, although the physical scores were lower than in the general population.
The following presentations addressed the challenge of organ shortage. Hasan Yersiz also from Los Angeles focused on splitting into extended right grafts and left lateral segments. In conclusion, the procedure is safe and beneficial, but its potential has not been fully realized yet. Many organs that could have been used for splitting are still transplanted as whole organs. Based on positive reports from Northern Italy, collaborations for sharing split livers have been advocated. Future allocation rules should support the split liver procedure. Dieter Broering from Kiel, Germany, reported results from the right and left lobe splitting procedure for two adult recipients and also emphasized the need for modification of the allocation rules. He cautioned the need for reconstruction of the middle hepatic vein and the high number of biliary complications. He proposed the following recipient criteria for this procedure: GRWR > 1%, MELD < 30, CIT < 10 hrs and recipient age < 60 years.
Based on the established feasibility of living donor liver transplantation, Kim Olthoff from Philadelphia raised the question, whether living donation in Western countries is an option for recipients with MELD scores above 30. Although long-term results in high MELD patients are comparable to low MELD recipients, the short-term results are clearly inferior and have to be weighed against the risk for the donor. The Eastern experience was presented by Yashuhiko Sugawara from Tokyo. He made a clear point that MELD scores don't accurately predict post liver transplantation mortality and therefore living donation is definitively an option in the absence of deceased donor organs.
Back to technical aspects, Michael Abecassis from Chicago clarified the terms of pure laparoscopic, hand-assisted laparoscopic and laparoscopic-assisted open (“hybrid”) procedures for the minimally invasive living donor hepatectomy. Based on his experience, he advocates the hybrid procedure, where the subcostal part of the incision can be avoided, but all safety components of the procedure are performed under direct view through an epigastric midline incision. In conclusion, operating room time, morbidity and total expenses were less than in conventional open surgery. Chung Mau Lo from Hong Kong, however, replied that independent of the surgical access living donor hepatectomy is still a maximally invasive procedure. Any increase in donor morbidity or mortality may jeopardize the concept of living donation.
In the closisng session, Charles Miller from Cleveland made the case for left lobe living donation. These grafts usually present with only one biliary duct, don't experience venous outflow complications, but sometimes demonstrate the need for arterial reconstruction or portal inflow modifications. The hepatic artery buffer response is a sequel of portal hyperperfusion in the “small-for-size syndrome”. The goal of inflow modification is to achieve a transhepatic pressure gradient of less than 10 mmHg and a portal flow of 1.5-2.5 cc/g/min. Possible measures include splenectomy or partial portal systemic shunting. Arterial vasodilatation (i.e. adenosine) may be a future treatment option. Referring to right lobe grafts, Koichi Tanaka from Kobe, Japan, payed close attention to the venous outflow congestion of the graft and advocated preoperative determination of the middle hepatic vein dominancy. Further he focused on biliary duct strictures as a common complication. The mean occurrence is at about 12 months post liver transplantation (2 to 36 months) and might be a sequel of the phagocytosis of absorbable suture material and subsequent cytokine release. Chao-Long Chen from Kaohsiung, Taiwan, also advocated the use of non-absorbable sutures to optimize the biliary reconstruction in microsurgical duct-to-duct anastomoses. The rate of biliary complications in living donor liver transplantation have markedly decreased to 9% with this technique.
Sheung Tat Fan from Hong Kong demonstrated several demanding procedures to optimize the venous outflow in living donor liver transplantation. In conclusion, the effort is well spent as the early patency rates are high.
The final debate related to the use of temporary portacaval shunting or application of a venovenous bypass. Nigel Heaton from London made a clear case for portacaval shunting, although published evidence is scarce. There were trends to shorter operative times, reduced requirements for blood products and stable mean arterial pressures during the anhepatic phase. Peter Neuhaus from Berlin, Germany, however, made the case for a caval replacement to prevent venous outflow congestion. The decision for conventional shunting should depend on circulatory parameters during the probative cross-clamping. In addition, he cautioned that most complications with conventional shunting may be avoided with an experienced team. Therefore, the use of a venovenous bypass should not be limited to the critically ill, high MELD patient.
To summarize the surgical sessions:
It's all about patient safety under today's and tomorrow's challenges.
Olaf Guckelberger.
Splenic artery reconstruction and pancreatic fistula: Mark Ghobrial comments on this challenging scenario. Go to Discussions to add your own views.
ILTS 15th Annual International Congress, New York
July 8 - 11, 2009
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All abstracts, as published in Liver Transplantation Annual Meeting Supplement
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