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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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Liver transplantation and liver resection as alternative treatments for primary hepatobiliary and secondary liver tumors: Competitors or allies?

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 111-116页

作者： jan lerut Institute for Experimental and Clinical Research(IREC) Universitécatholique Louvain(UCL)Avenue Hippocrate 561200 Woluwe Saint PierreBrusselsBelgium

Although Starzl designed in the 1960’s liver transplantation(LT)to treat unresectable primary and also secondary liver tumors,transplantation still occupies a(too)small place in the respective therapeutic algorithms[1].Due to the lack of(any)selection criteria,the concept of transplantation became rapidly challenged because of the prohibitively high incidence of tumor recurrence[1–3].

关键词： liver tumors Liver

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Living donor liver transplantation:A complex but worthwhile undertaking

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Hepatobiliary & Pancreatic Diseases International 2020年第4期19卷 305-306页

作者： jan lerut Institute for Experimental and Clinical Research(IREC) Universitécatholique Louvain(UCL)Avenue Hippocrate 551200 BrusselsBelgium

Since its’first applications in clinical pediatric and adult liver transplantation practice by Strong et *** Makuuchi in 1989[1,2],living donor liver transplantation(LDLT)has been an ever increasing part of the today’s practice of liver *** on different donor demographics(living donation *** donation)and on much larger experiences with partial liver resection(aggressive resection in cirrhotic patients versus non-surgical,locoregional treatments),LDLT merely developped in Asian *** nowadays,this technique accounts for more than 90%of the transplantation activity in the Eastern hemisphere,whereas it accounts only for 5%of activities in the Western one[3,4].

关键词： donor Eastern Strong

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Modern technology,liver surgery and transplantation

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Hepatobiliary & Pancreatic Diseases International 2022年第4期21卷 307-309页

作者： jan lerut Institut de Recherche Expérimentale et Clinique Universitécatholique de LouvainAvenue Hippocrate 551200BrusselsBelgium

Since the first right hepatectomy performed by Jean-Louis Lortat-Jacob on October 16,1951 and the first liver transplantation by Thomas Earl Starzl on March 1,1963,hepatobiliary surgery and liver transplantation had a spectacular development[1,2].After the hesitating beginning in the 1950’s and 1960’s,their evolution really took off in the 1980’,reaching high-speed velocity in the 21st century.

关键词： surgery liver really

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Morphology does not tell us the entire story: biological behavior improves our ability to select patients with hepatocellular carcinoma waiting for liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2015年第6期14卷 570-571页

作者： jan lerut Quirino Lai Starzl Unit of Abdominal Transplantation Université catholique Louvain (UCL)

The Milan criteria （solitary lesion 〈5 cm or twothree lesions 〈3 cm）, published in 1996 in relation to the selection of patients harboring hepatocel-lular carcinoma （HCC） in a diseased liver are still dominating the allocation of liver allografts in all international organ allocation organisms, this despite the fact that excellent results have been reported after liver transplantation （LT） done for patients presenting HCC outside these criteria,

关键词： HCC AFP Morphology does not tell us the entire story

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Composite hepatocellular and hemangiosarcomatous tumor: The prognosis is determined by the sarcomatous component

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Hepatobiliary & Pancreatic Diseases International 2020年第2期19卷 184-186页

作者： Giuseppe Orlando Quirino Lai jan lerut Department of General Surgery Wake Forest University School of MedicineWinston-SalemNCUSA Wake Forest Institute for Regenerative Medicine Wake Forest University School of MedicineWinston-SalemNCUSA Universitecatholique de LouvainBrusselsBelgium Department of General Surgery and Organ Transplantation Sapienza University of RomeRomeItaly

Nowadays, mixed liver tumors are more frequently diagnosed due to better imaging, advanced immunohistochemistry (IHC) staining techniques and better knowledge of hepatic tumorigene- sis [1–3] . Such tumors represent a mosaic of components with dis- tinct histogenesis and carcinogenic pathways. As their occurrence in the liver is very rare, their behavior and natural history are difficult to determine, and their management remains empirical. An uncommon case of a composite tumor harboring hepatocellular carcinoma (HCC) and hepatic hemangiosarcoma (HHS) components in a liver transplant (LT) recipient is reported herein.

关键词： sarcoma hepatocellular hepatic

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Bilateral proficiency over time leads to reduced donor morbidity in living donor hepatectomy

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Hepatobiliary Surgery and Nutrition 2020年第3期9卷 339-341页

作者： jan P.lerut Institut de Recherche Expérimentale et Clinique(IREC) Universitécatholique Louvain(UCL)BrusselsBelgium

In this issue of HSN,the very reputed Kaohsiung Liver Transplantation Center in Taiwan led by ***-Long Chen reports about its extensive experience in the field of adult living donor liver transplantation(aLDLT).

关键词： donor Liver morbidity

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Total hepatectomy and modified temporary porto-caval shunt as a useful bridge to urgent retransplantation

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Hepatobiliary & Pancreatic Diseases International 2018年第4期17卷 376-377页

作者： Samuele Iesari Maxime Foguenne jan lerut Starzl Abdominal Transplant Unit University Hospitals Saint-LucUniversité catholique de Louvain Department of Biotechnological and Applied Clinical Sciences University of L'Aquila

To the Editor:The original technique of liver transplantation(LT)described by Starzl in 1963 included the removal of the recipient inferior vena cava(IVC)with use of extracorporeal veno-venous bypass(VVB).Since then,the majority of transplant centres evolved towards an IVC sparing hepatectomy with or without temporary porto-caval shunting(PCSh)[1].

关键词： LIVER-TRANSPLANTATION

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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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Complex hepatic outflow reconstruction in domino liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2014年第1期13卷 98-100页

作者： Rafael S Pinheiro Quirino Lai Carola Dahrenmoller jan lerut Starzl Unit of Abdominal Transplantation University Hospitals Saint Luc Université Catholique Louvain UCL Brussels Belgium Department of Gastroenterology So Paulo University School of Medicine So Paulo Brazil

Domino liver transplantation has been accepted as a safe procedure to further expand the organ donor pool. The most important technical challenge of the procedure resides in restoring a proper hepatic venous allograft outflow in the familial amyloidotic polyneuropathy-liver recipient. To overcome this issue, combined techniques were used to perform an innovative outflow reconstruction. A domino liver transplantation was successfully performed with reconstruction of complex venous outflow. The inferior vena cava sparing hepatectomy technique in the familial amyloidotic polyneuropathy-donor was used to cut the hepatic vein to the liver parenchyma. To overcome this issue the venous outflow tract was reconstructed using a longitudinally opened iliac vein graft from a post-mortem donor to create a new outflow tract using a diamond patch between the right and middle/left hepatic veins.

关键词： liver transplantation intraoperative anatomy hepatic vein

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