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Advancing immunosuppression in liver transplantation: A narrative review

Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 441-448页

作者： Samuele Iesari Francesca Laura Nava Ilaria Elena Zais laurent coubeau Mariano Ferraresso Evaldo Favi Jan Lerut General Surgery and Kidney Transplantation Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico15 Via della Commenda20122 MilanItaly Institut de Recherche Expérimentale et Clinique Universitécatholique de Louvain10 Avenue Hippocrate1200 BrusselsBelgium Service de Chirurgie et Transplantation Abdominale Cliniques Universitaires Saint-Luc55 Avenue Hippocrate1200 BrusselsBelgium Department of Clinical Sciences and Community Health Universitàdegli Studi di Milano19 Via della Commenda20122 MilanItaly

Immunosuppression is essential to ensure recipient and graft survivals after liver transplantation(LT). However, our understanding and management of the immune system remain suboptimal. Current immunosuppressive therapy cannot selectively inhibit the graft-specific immune response and entails a significant risk of serious side effects, i.e., among others, de novo cancers, infections, cardiovascular events, renal failure, metabolic syndrome, and late graft fibrosis, with progressive loss of graft function. Pharmacological research, aimed to develop alternative immunosuppressive agents in LT, is behind other solidorgan transplantation subspecialties, and, therefore, the development of new compounds and strategies should get priority in LT. The research trajectories cover mechanisms to induce T-cell exhaustion, to inhibit co-stimulation, to mitigate non-antigen-specific inflammatory response, and, lastly, to minimize the development and action of donor-specific antibodies. Moreover, while cellular modulation techniques are complex, active research is underway to foster the action of T-regulatory cells, to induce tolerogenic dendritic cells, and to promote the function of B-regulatory cells. We herein discuss current lines of research in clinical immunosuppression, particularly focusing on possible applications in the LT setting.

关键词： Liver transplantation Immunosuppression Drug development Long-term results Clinical operational tolerance

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Meso-Rex bypass for the management of extrahepatic portal vein obstruction in adults(with video)

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Hepatobiliary & Pancreatic Diseases International 2022年第1期21卷 25-32页

作者： Martin Brichard Samuele Iesari Jan Lerut Raymond Reding Pierre Goffette laurent coubeau Service de Chirurgie et Transplantation Abdominale Cliniques Universitaires Saint-LucUniversitéCatholique de Louvain10 Avenue HippocrateBrussels 1200Belgium Pôle de Chirurgie Expérimentale et Transplantation Institut de Recherche Expérimentale et CliniqueUniversitéCatholique de LouvainBrusselsBelgium Department of Clinical Sciences and Applied Biotechnology University of L’AquilaL’AquilaItaly Department of General Surgery and Kidney Transplantation Fondazione IRCCS Ca’Granda Ospedale Maggiore PoliclinicoMilanItaly Service de Radiologie et Imagerie médicale Cliniques Universitaires Saint-LucUniversitéCatholique de LouvainBrusselsBelgium

Background:Extrahepatic portal vein obstruction(EHPVO)results in severe portal hypertension(PHT)leading to severely compromised quality of ***,pharmacological and endoscopic management is unable to solve this *** hepatic portal flow using meso-Rex bypass(MRB)may solve *** procedure,uncommon in adult patients,is considered the treatment of choice for EHPVO in ***:From 1997 to 2018,8 male and 6 female adults,with a median age of 51 years(range 22-66)underwent MRB procedure for EHPVO at the University Hospitals Saint-Luc in Brussels,***-toms of PHT were life altering in all but one patient and consisted of repetitive gastro-intestinal bleedings,sepsis due to portal biliopathy,and/or severe abdominal *** surgical technique consisted in interposition of a free venous graft or of a prosthetic graft between the superior mesenteric vein and the Rex recess of the left portal ***:Median operative time was 500 min(range 300-730).Median follow-up duration was 22 months(range 2-169).One patient died due to hemorrhagic shock following percutaneous transluminal interven-tion for early graft *** morbidity,defined as Clavien-Dindo score≥III,was 35.7%(5/14).Shunt patency at last follow-up was 64.3%(9/14):85.7%(6/7)of pure venous grafts and only 42.9%(3/7)of prosthetic *** relief was achieved in 85.7%(12/14)who became asymptomatic after ***:Adult EHPVO represents a difficult clinical condition that leads to severely compromised quality of life and possible life-threatening *** such patients,MRB represents the only and last resort to restore physiological portal vein *** successful in a majority of patients,this procedure is associated with major morbidity and mortality and should be done in tertiary centers expe-rienced with vascular liver surgery to get the best results.

关键词： Meso-Rex bypass Extrahepatic portal vein obstruction Extrahepatic portal hypertension Portal vein thrombosis Surgical procedure

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Indocyanine green fluoroscopy and liver transplantation:a new technique for the intraoperative assessment of bile duct vascularization

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Hepatobiliary & Pancreatic Diseases International 2017年第4期16卷 440-442页

作者： laurent coubeau Julie Frezin Romain Dehon Jan Lerut Raymond Reding Starzl Unit Abdominal Transplantation Department of Abdominal and Transplantation SurgeryCliniques Universitaires Saint LucUniversitécatholique Louvain(UCL)BrusselsBelgium Pathology Unit Cliniques Universitaires Saint LucUniversitécatholique Louvain(UCL)BrusselsBelgium

To the Editor:Biliary tract complications remain the Achilles’heel of liver transplantation（LT）;and the transplant commu nity is exploring ways of tackling this problem.A well vascularized bile duct is a prerequisi... 详细信息

关键词： ICG by is it from of for

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Insights in living-donor liver transplantation associated with two-stage total hepatectomy:First case in neuroendocrine tumor metastases and functional assessment techniques

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Hepatobiliary & Pancreatic Diseases International 2022年第4期21卷 392-395页

作者： laurent coubeau Samuele Iesari Paulina Henry Philippe D’Abadie Aude Vanbuggenhout Raymond Reding aTransplantation Abdominale Cliniques Universitaires Saint-LucUniversite catholique de LouvainBrusselsBelgium Pole de Chirurgie Experimentale et Transplantation Institut de Recherche Experimentale et CliniqueUniversite catholique de LouvainBrusselsBelgium Department of Biotechnological and Applied Clinical Sciences University of L’AquilaL’AquilaItaly Service d’anatomo-pathologie Cliniques Universitaires Saint-LucUniversite catholique de LouvainBrusselsBelgium Service de medecine nucleaire Cliniques Universitaires Saint-LucUniversite catholique de LouvainBrusselsBelgium

To the Editor:While organ shortage commonly dooms patients on waiting list,alternative options as living-donor liver transplantation(LDLT)are assiduously *** principles of liver surgery rule LDLT:there must be suffici... 详细信息

关键词： donor liver surgery

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Secondary non-resectable liver tumors:A single-center living-donor and deceased-donor liver transplantation case series

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Hepatobiliary & Pancreatic Diseases International 2019年第5期18卷 412-422页

作者： Jan Lerut Samuele Iesari Gaetan Vandeplas Tiziana Fabbrizio Kevin Ackenine Milton Eduardo Inostroza Nunez Mina Komuta laurent coubeau Olga Ciccarelli Eliano Bonaccorsi-Riani BrusselsBelgium Department of Biotechnological and Applied Clinical Sciences University of L’AquilaL’AquilaItaly Starzl Abdominal Transplant Unit University Hospitals Saint-LucUniversité catholique de LouvainBrusselsBelgium Hepatobilio-pancreatic Unit Las Higueras HospitalTalcahuanoChile Department of Pathology University Hospitals Saint-LucUniversite catholique de LouvainBrusselsBelgium

Background: During the last decades, deceased-donor liver transplantation (DDLT) has gained a place in the therapeutic algorithm of well-selected patients harbouring non-resectable secondary liver tumors. Living-donor LT (LDLT) might represent a valuable means to further expand this indication for LT. Methods: Between 1985 and 2016, twenty-two adults were transplanted because of neuroendocrine ( n = 18, 82%) and colorectal metastases ( n = 4, 18%);50% received DDLT and 50% LDLT. In LDLT, 4 (36%) right and 7 (64%) left grafts were used;the median graft-to-recipient-weight ratios (GRWR) were 1.03%(IQR 0.86%- 1.30%) and 0.59%(IQR 0.51%- 0.91%), respectively. Median post-LT follow-up was 64 months (IQR 17–107) in the DDLT group and 40 months (IQR 35–116) in the LDLT group. DDLT and LDLT recipients were compared in terms of overall survival, graft survival, postoperative complications and recurrence. Results: The 1- and 5-year actuarial patient survivals were 82% and 55% after DDLT, 100% and 100% after LDLT, respectively ( P < 0.01). One- and 5-year actuarial graft survivals were 73% and 36% after DDLT, 91% and 91% after LDLT ( P < 0.01). The outcomes of right or left LDLT were comparable. Donor hepatectomy proved safe, and one donor experienced a Clavien IIIb complication. Bilirubin peak was significantly lower after left hepatectomy compared with that after right hepatectomy [1.3 (IQR 1.2–2.2) vs. 3.3 (IQR 2.3–5.2) mg/dL;P = 0.02]. Conclusions: The more recent LDLT series compared favorably to our DDLT series in the treatment of secondary liver malignancies. The absence of portal hypertension and the use of smaller left grafts make recipient and donor surgeries safe. The safety of the procedures and lack of interference with the scarce allograft pool are expected to lead to a more frequent use of LDLT in the field of transplant oncology.

关键词： Colorectal cancer Living-donor liver transplantation Liver metastasis Neuroendocrine tumor Secondary liver tumors

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Adult-to-adult living-donor liver transplantation: The experience of the Université catholique de Louvain

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Hepatobiliary & Pancreatic Diseases International 2019年第2期18卷 132-142页

作者： Samuele Iesari Milton Eduardo Inostroza Nú?ez Juan Manuel Rico Juri Olga Ciccarelli Eliano Bonaccorsi-Riani laurent coubeau Pierre-Fran?ois Laterre Pierre Goffette Chantal De Reyck Beno?t Lengelé Pierre Gianello Jan Lerut Starzl Abdominal Transplant Unit Cliniques Universitaires Saint-Luc Institut de Recherche Expérimentale et Clinique Université catholique de Louvain Department of Biotechnological and Applied Clinical Sciences University of L’Aquila Hepatobiliopancreatic Unit Las Higueras Hospital Cirugía de Trasplantes Centro Médico Imbanaco Department of Intensive Care Cliniques Universitaires Saint-Luc Université catholique de Louvain Department of Radiology Cliniques Universitaires Saint-Luc Université catholique de Louvain Department of Plastic and Reconstructive Surgery Cliniques Universitaires Saint-Luc Université catholique de Louvain P?le de Chirurgie Expérimentale et Transplantation Institut de Recherche Expérimentale et Clinique Université catholique de Louvain

Background: Liver transplantation is the treatment for end-stage liver diseases and well-selected malignancies. The allograft shortage may be alleviated with living donation. The initial UCLouvain experience of adult living-donor liver transplantation(LDLT) is presented. Methods: A retrospective analysis of 64 adult-to-adult LDLTs performed at our institution between 1998 and 2016 was conducted. The median age of 29(45.3%) females and 35(54.7%) males was 50.2 years(interquartile range, IQR 32.9–57.5). Twenty-two(34.4%) recipients had no portal hypertension. Three(4.7%) patients had a benign and 33(51.6%) a malignant tumor [19(29.7%) hepatocellular cancer, 11(17.2%) secondary cancer and one(1.6%) each hemangioendothelioma, hepatoblastoma and embryonal liver sarcoma]. Median donor and recipient follow-ups were 93 months(IQR 41–159) and 39 months(22–91), respectively. Results: Right and left hemi-livers were implanted in 39(60.9%) and 25(39.1%) cases, respectively. Median weights of right-and left-liver were 810 g(IQR 730–940) and 454 g(IQR 394–534), respectively. Graft-to-recipient weight ratios(GRWRs) were 1.17%(right, IQR 0.98%-1.4%) and 0.77%(left, 0.59%-0.95%). One-and five-year patient survivals were 85% and 71%(right) vs. 84% and 58%(left), respectively. Oneand five-year graft survivals were 74% and 61%(right) vs. 76% and 53%(left), respectively. The patient and graft survival of right and left grafts and of very small( < 0.6%), small(0.6%–0.79%) and large( ≥0.8%) GRWR were similar. Survival of very small grafts was 86% and 86% at 3-and 12-month. No donor died while five(7.8%) developed a Clavien–Dindo complication IIIa, IIIb or IV. Recipient morbidity consisted mainly of biliary and vascular complications; three(4.7%) recipients developed a small-for-size syndrome according to the Kyushu criteria. Conclusions: Adult-to-adult LDLT is a demanding procedure that widens therapeutic possibilities of many hepatobiliary diseases. The donor procedure can be done safely

关键词： Liver transplantation Living-donor Hepatocellular cancer Secondary liver tumor Small-for-size syndrome Small-for-size graft

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Successful emergency resection of a massive intra-abdominal hemophilic pseudotumor

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World Journal of Gastrointestinal Surgery 2015年第3期7卷 43-46页

作者： Julie Frezin Lancelot Marique laurent coubeau Catherine Hubert Catherine Lambert Cédric Hermans Nicolas Jabbour Department of Abdominal Surgery and Transplantation Cliniques Universitaires Saint-Luc Department of Hematology Cliniques Universitaires Saint-Luc

An intra-abdominal pseudotumor is a rare complication of hemophilia. Surgical treatment is associated with high morbidity and mortality rates and reported cases are scarce. We present a 66-year-old Caucasian male suffering from severe hemophilia type A treated for 10 years with Factor Ⅷ. Major complications from the disease were chronic hepatitis B and C, cerebral hemorrhage and disabling arthropathy. Twenty-three years ago, retro-peritoneal bleeding led to the development of a large intra-abdominal pseudotumor, which was followed-up clinically due to the high surgical risk and the lack of clinical indication. The patient presented to the emergency department with severe sepsis and umbilical discharge that had appeared over the past two days. Abdominal computed tomography images were highly suggestive of a bowel fistula. The patient was taken to the operating room under continuous infusion of factor Ⅷ. Surgical exploration revealed a large infected pseudotumor with severe intra-abdominal adhesions and a left colonic fistula. The pseudotumor was partially resected en bloc with the left colon leaving the posterior wall intact. The postoperative period was complicated by septic shock and a small bowel fistula that required reoperation. He was discharged on the 73 rd hospital day and is well 8 mo after surgery. No bleeding complications were encountered and we consider surgery safe under factor Ⅷ replacement therapy.

关键词： Hemophilia A Hemophilic pseudotumor Colonic fistula Factor Ⅷ replacement therapy Surgeryin hemophilic patient

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