The 27th Annual Congress of the International Liver Transplantation Society (ILTS) was held between May 4 and 7, 2022, in a hybrid format in Istanbul, Turkey.
In this report, we aim to present the most stimulating, enriching, and relevant topics discussed during the meeting. Topics covered oral (O) abstracts, including late breaking (LB) abstracts, symposia, and other forums. The selection of content was not based on the level of evidence of the studies but rather on the fact that they received much attention and were discussed elaborately. Evolution of the number and frequency of abstracts on clinical topics over time is presented in Table 1. Machine preservation in the deceased donor liver transplantation (LT) setting, including donation after circulatory death abstracts, has not been included in this summary because this section has been covered by the Basic Science Committee of the ILTS.1 Gender representation of moderators and speakers is depicted in Figure 1A and 1B. The abstract identifier is included in the text, and the invited lectures are referenced by the name of the presenter. All presentations can be reviewed on the ILTS website learning platform (https://ilts.org/education/).
TABLE 1. -
Absolute number and frequencies of clinical abstracts, per topic, presented at the Joint-ILTS LICAGE meetings 2017–2022
|Acute liver failure/anesthesia/critical care medicine
|Viral hepatitis/alcoholic liver diseases/NASH/NAFLD
|Patient selection/organ allocation/organ recovery
|Donation after circulatory death/machine perfusion
COVID-19, coronavirus disease 2019; ILTS, International Liver Transplant Society; LICAGE, Liver Intensive Care Group of Europe; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis.
SURGICAL TECHNIQUE/LIVING DONOR LT
Strategies to optimize patients for right lobe hepatectomy were discussed. The first publication in 2012 (25 cases) showed that associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was a robust operation for patients who require optimization of a functional liver remnant (Dr Petrowsky).2 Further data from the Zurich-ALPPS registry suggest that with accumulating experience (over 1000 cases in the registry), there has been a dramatic reduction in morbidity and 90-d mortality from 20% to 40% and 16% to 10% and 4%, respectively.3,4 Purported reasons for this remarkable improvement in outcomes included a better selection of patients along with modifications to the operation and a better understanding of liver regeneration. It was also noted that improved outcomes were observed when the timing for the second stage was flexible and based on anatomical and functional liver testing rather than on dogmatic timelines. Partial ALPPS showed equal volumetric growth as total ALPSS when at least 50% of liver partition was performed and may be a less invasive alternative to ALPPS (Dr Di Benedetto).4
Another technique to achieve adequate functional liver remnant hypertrophy and to avoid posthepatectomy liver failure is liver venous deprivation (LVD) obtained with preoperative transjugular embolization of the right hepatic vein and ipsilateral portal vein. This combined venous embolization achieves higher regeneration and better recovery of liver function than just portal vein embolization (Dr Nadalin).5 Mechanism of action includes an increased pressure in the nonembolized liver and formation of intrahepatic collaterals with augmented damage of the embolized liver, all of which result in amplified regeneration. Despite an increased risk of enlarging venovenous collateral, LVD has been shown to result in shorter operation times and less bleeding. LVD has often been compared with ALPPS; however, the mechanisms of action are different in the 2 procedures. In contrast to LVD, ALPPS results in a portal flow redistribution, which promotes a release of proliferative factors. The parenchymal transection further interrupts intrahepatic collaterals and activates an inflammatory response. The only large study that compared the 2 techniques showed that hypertrophy was faster for ALPPS. Successful resection rates were 72.6% for LVD versus 90.6% for ALPPS (P < 0.001).6 Operative duration, blood loss, and length of stay were lower for LVD, whereas 90-d major complications and mortality were comparable.
In pediatric LT recipients weighing <5 kg, it is not uncommon to have a large liver graft with a graft-to-recipient weight ratio of >4. The merits of minimally invasive surgery especially for standard LLS resection have been unequivocally demonstrated by meta-analyses, consensus guidelines, and recommendations.7,8 However, challenging technical aspects of anatomical graft reduction, like dissection of the segment II or III portal pedicle, may have a steep learning curve with a conventional laparoscopic approach. Robotic surgery allows this barrier to be broken. It replicates and sometimes surpasses the view and surgical precision achieved in open surgery. An added advantage is the presence of the image-guided surgery (inbuilt indocyanine green camera) that enables an accurate anatomical delineation of perfused liver segments. The report by Rela et al highlights the relative ease of hilar dissection with the robotic platform, especially for transplant surgeons who may not be experts at advanced laparoscopic surgery. In the report, in situ reduction was performed with an aim to accurately demarcate the revascularized segments, to reduce cold ischemia time, and, most importantly, to reduce the risk of bleed, which in very small children may be relatively massive.9
Robotic hepatectomy outcomes were evaluated in 2 studies. In the first, they reported 115 right, 7 left, and 8 left lateral segment robotic donor hepatectomy procedures. The operative time was shorter with experience, and no cases were converted to an open approach. The most common complications were bile leak (4.3%) and bleeding requiring transfusion (2.6%). The rate of serious complications was 7.0%, with zero mortality (LB-O-06). In the second, 118 open left lateral segment hepatectomies (LLSHs) versus 40 robotic-LLSH for living donor LT (LDLT) were reported; the duration of surgery was longer in the robotic-LLSH, whereas intraoperative blood loss was lower. Morphine consumption was also significantly lower in the robotic-LLSH group. There was no difference in the length of hospital or intensive care unit stay (O-021).
Regarding coronavirus disease 2019 infection in the LT setting, immunosuppression (IS) discontinuation is not recommended, whereas for moderate to severe disease, mycophenolate mofetil may be reduced or discontinued because this has been associated with more favorable outcomes.10 Remdesivir is safe and effective in LT recipients. There is a risk of late secondary infections (fungal, mucormycosis, etc) in LT patients who have received dexamethasone or immunomodulatory therapies. Antibody/cellular responses seem more vigorous with pre-LT vaccination than post-LT.
A multisociety survey showed that coronavirus disease 2019 vaccination was almost universal in LT recipients, mostly with mRNA vaccines. However, only 33% of centers reported specific monitoring policies to assess postvaccination efficacy and safety. Sixty-six percent of centers reported cases of severe acute respiratory syndrome coronavirus 2 infection postvaccination and 33% severe (O-068).
Dr Stock focused on HIV patients and concluded that in the direct-acting antivirals era, HIV-infected and -uninfected patients displayed comparable outcomes.11,12
DONOR AND PATIENT SELECTION/ORGAN ALLOCATION/OUTCOMES
Dr Van Rosmalen revised the policy for donors with previous nonhepatic malignancies in terms of balancing the risk of malignancy transmission and waitlist mortality.13 The use of older donors was discussed (Dr Heimbach), including a higher risk of unanticipated malignancy, the presence of vascular calcifications, and the fact that donor graft size and rate of regeneration are reduced.14 Organs with moderate steatosis from younger donors with shorter cold ischemia time can be safely used in LT recipients with a low-medium Model for End-stage Liver Disease (MELD) (Dr Hernandez-Alejandro). Furthermore, machine perfusion and the manipulation of lipid metabolism during machine perfusion are promising tools to increase the utilization of steatotic organs.15,16
Organ allocation is a continuing conundrum in 2022 (Dr Segev). Using computational tools to create a composite allocation score will balance medical urgency, posttransplant survival, candidate biology, patient access, and patient efficiency. MELD allocation models fail to take into account most of these characteristics.17
Several presentations highlighted the use of advanced machine learning or “artificial intelligence” approaches. A deep learning model to predict trajectories of waitlisted nonalcoholic steatohepatitis cirrhotic patients was presented.18 Compared with the Cox model, DeepHit was superior in predicting short-term outcomes at 1 mo (C-index 0.924 versus 0.823 for death, and 0.896 versus 0.832 for LT), but DeepHit did not retain this advantage for 1-y outcomes (C-index 0.788 versus 0.778 for death, and 0.788 versus 0.802 for LT) (LB-O-09). Another artificial intelligence model to predict rejection and infection in patients after LT (LB-O-03) was presented. The Early Liver Retransplantation Score underscores the importance of matching donors to recipients to maximize graft longevity (LB-O-10).
Across the world, there is lack of equity of access to LT for patients with acute-on-chronic liver failure (ACLF).19 The CHANCE study is a prospective, observational, multicenter study aiming to compare graft and patient survival rates post-LT in patients with ACLF grade 2 (ACLF-2) and ACLF-3 at LT with patients with decompensated cirrhosis without ACLF, and transplant-free survival of patients with ACLF-2 and ACLF-3 not listed for LT (Dr Jalan). There are important unanswered questions (lack of intention-to-treat results from the time of waitlisting, detailed information about waiting list outcomes, or characteristics of donor organ to ensure good outcomes among others), and it is expected that this ongoing study would help to clarify and improve access and outcomes.
Frailty was the topic of the well-attended Vanguard Featured Symposium. Frailty can be measured with tools that assess constructs of physical strength/function, aerobic capacity, or physical disability (Dr Tandon); can be used to stratify prehabilitation; and help in decision-making.20 Frailty in patients with ACLF is mainly driven by the sarcopenia component and has a deleterious impact on outcomes.21 It is usually assessed by muscle computed tomography measurements. Thigh ultrasound, bioimpedanciometry, and liver frailty index may be helpful (Dr Campos-Varela). The definition of frailty in pediatric LT is even more challenging because the measure of physical activity is difficult (Dr Kasahara).
One oral abstract showed the persistence of sarcopenia post-LT, with risk factors being male gender, advanced age, and need for rehabilitation in the first 6 mo posttransplant (O-046).
There were a few abstracts regarding less prevalent diseases that warrant mention. Two abstracts were related to Budd-Chiari syndrome. A study from the European Liver Transplant Registry showed the highest survival in the most recent 5-y era while recipient age, MELD, and donor age were associated with worse outcome, with anticoagulation improving outcomes (O-047). From the US United Network for Organ Sharing registry, there was no survival difference in patients with transjugular intrahepatic portosystemic shunts pre-LT versus no transjugular intrahepatic portosystemic shunt. Risk of mortality increased with history of diabetes, higher donor risk index, and African American race (O-049).22 For patients with Fontan disease and induced liver disease, combined heart-liver transplant is a potential therapy; however, the outcomes can be poor when compared with non-Fontan patients (O-051).
ANESTHESIOLOGY/CRITICAL CARE/ACUTE LIVER FAILURE
Dr Wendon reviewed the past 30 y of LT in acute liver failure (ALF). The talk focused on appropriate selection, which prevents false-positives, unnecessary transplantation, and false-negatives that would miss the opportunity to benefit from LT and result in death. In summary, the criteria are robust for hyperacute and “acute” liver failure, but their application remains variable. Regarding ALF management, it was shown that the 13-C-methacetin breath test could be effective in predicting hepatic recovery (Dr Carvellas).23 The ILTS-ALF survey (267 participants) showed that although 85% of centers agree on LT with the presence of hepatic encephalopathy, only 34% proceed with LT in the presence of liver injury without hepatic encephalopathy (Dr Gurkar).
It was debated that enhanced recovery after surgery is a noble goal in high acuity LT but should be aspirational rather than expected (Dr Orloff and Dr Brown). Compliance with the pathway should not be used as a measure of success as in other more planned enhanced recovery after surgeries.
The application of extracorporeal membrane oxygenation for adult LT recipients with cardiopulmonary failure was presented. Septic shock as an indication, learning curve, and pretransplant total bilirubin ≥5 mg/dL predicted in-hospital mortality (O-030).24
Treating asymptomatic high-risk coronary artery disease is beneficial as compared with medical therapy, with a low risk of procedural complications (Dr Crespo).25,26
The pediatric LT sessions focused on the multidisciplinary approach to decrease waitlist mortality and increase access to LT for pediatric recipients, as well as on how to improve short- and long-term outcomes. The role of portal vein pressure (PVP) measurement in pediatric LDLT and its impact on posttransplant outcomes was discussed (LB-O-14). Patient (100% versus 94.8%) and graft (100% versus 93%) survival were significantly better in patients with PVP measurement. Patients with PVP >25 mm Hg before implantation had higher portal vein flow. However, high PVP before abdominal closure did not influence clinical outcomes.
Bridging or downstaging therapies for hepatocellular carcinoma (HCC) before LT included sorafenib, with important limitations in terms of side effects, immune checkpoint inhibitors with the concern about T-cell activation and rejection,27 transarterial chemoembolization (TACE), and radioembolization (TARE). The median time to response for TARE is 4.2 versus 10.9 mo for TACE, suggesting that TARE may be helpful in reducing time to LT.28 Although time to progression is longer with TARE, it does not result in survival difference.29
A multicenter, retrospective study including 259 patients showed that upfront-LDLT and a downstaging approach both offered acceptable outcomes for HCC beyond University of California, San Francisco criteria. Upfront-LDLT patients had better intention-to-treat overall survival with a lower risk of dropout. With downstaging, 33% of patients had no viable tumor and 33% had tumors within Milan criteria; these reduced the risk of long-term recurrence (O-087). Data from European Liver Transplant Registry reported the outcomes of LT for combined HCC-cholangiocarcinoma tumors in 115 patients. Five-year overall survival was low (37%) and tumor recurrence high (42%); however, 5-y survival rate was 69% in patients within Milan criteria with AFP ≤20 ng/mL (O-093).
The Radiology Workshop focused on the role of interventional radiological techniques for the management of posttransplant complications. The usage of biodegradable stents and the creation of intrahepatic biliary connections using a microwave for drainage of disconnected ductal systems following post-LT biliary strictures were demonstrated (Dr Kutlu).
From the pathologist’s perspective, the challenges encountered in diagnosing antibody-mediated rejection in a liver biopsy were well highlighted. Antibody-mediated rejection is a small but significant contributor to graft loss, and the Pathology Working Group Committee unanimously agreed that the Achilles heel lies in its early identification with protocol biopsies and specialized donor-specific HLA antibodies and C4d staining.30
Seventy percent of long-term deaths are because of comorbidities, mainly related to side effects of IS. Reducing the dose of tacrolimus is safe in the presence of a second drug, such as mammalian target of rapamycin inhibitors or mycophenolate mofetil. Interestingly, protocol liver biopsy in adult LT recipients with completely normal liver tests has shown that 20% of the patients had fibroinflammatory changes with a molecular profile (similar to clinical T cell–mediated rejection) (Dr Aluvihare).
In a study evaluating liver allograft fibrosis (LAF) in 139 pediatric LT recipients (174 liver biopsies), 91% of patients demonstrated LAF (9% severe). The independent risk factors associated with LAF were episodes of acute cellular rejection and biliary problems, among others. Additionally, low tacrolimus levels and LAF were associated, and under IS may contribute to fibrosis development (O-070). The overall success rate of tolerance is 12% at 10.5 y and 9.3% at 8 y after LT for adults and pediatrics, respectively.31 However, because most of the adverse effects of IS occur early, the benefit of complete withdrawal of IS at 8 to 10 y post-LT remains debatable (Dr Shaked). Rejection can be detected and even predicted using cell-free DNA, micro-RNA, and a particular combination of genes. Other noninvasive markers that can identify subclinical T cell–mediated rejection are the combination of liver tests, elastography, and donor-specific antibodies.32,33
The merits and limitations of big data were discussed in the Vanguard Debate session (Dr Mulligan and Dr Liu). Although it was agreed that small sample sizes have long been an inevitable Achilles heel in transplantation research and that large collaborative data registries can be a potential solution, it was underscored that big, collaborative databases often lose granularity.
The equality, diversity, and inclusion ILTS committee presented results from a survey including 38 countries (199 responses, 15.2% response rate). Thirty-five percent of responders experienced some form of discrimination during training/practice related to gender (21%), race (14%), or country of origin (12%), and 43.7% did not have support from a mentor. Female transplant professionals experienced significantly more discrimination (P < 0.001). Among the responders, women occupied only 22% of the leadership positions, with surgical specialties being the least favorable (P < 0.001). Based on these results, the equality, diversity, and inclusion ILTS committee proposed the promotion of underrepresented groups, creation of mentorship programs, and creation of maternity/paternity leave policies (O-018).34
The authors thank Marina Berenguer, Mohamed Rela, and Mark Ghobrial for their contributions and critical appraisal of the article.
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