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Gadour E. Lesson learnt from 60 years of liver transplantation: Advancements, challenges, and future directions. World J Transplant 2025; 15:93253. [PMID: 40104199 PMCID: PMC11612893 DOI: 10.5500/wjt.v15.i1.93253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 09/06/2024] [Accepted: 09/14/2024] [Indexed: 11/26/2024] Open
Abstract
Over the past six decades, liver transplantation (LT) has evolved from an experimental procedure into a standardized and life-saving intervention, reshaping the landscape of organ transplantation. Driven by pioneering breakthroughs, technological advancements, and a deepened understanding of immunology, LT has seen remarkable progress. Some of the most notable breakthroughs in the field include advances in immunosuppression, a revised model for end-stage liver disease, and artificial intelligence (AI)-integrated imaging modalities serving diagnostic and therapeutic roles in LT, paired with ever-evolving technological advances. Additionally, the refinement of transplantation procedures, resulting in the introduction of alternative transplantation methods, such as living donor LT, split LT, and the use of marginal grafts, has addressed the challenge of organ shortage. Moreover, precision medicine, guiding personalized immunosuppressive strategies, has significantly improved patient and graft survival rates while addressing emergent issues, such as short-term complications and early allograft dysfunction, leading to a more refined strategy and enhanced post-operative recovery. Looking ahead, ongoing research explores regenerative medicine, diagnostic tools, and AI to optimize organ allocation and post-transplantation car. In summary, the past six decades have marked a transformative journey in LT with a commitment to advancing science, medicine, and patient-centered care, offering hope and extending life to individuals worldwide.
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Affiliation(s)
- Eyad Gadour
- Department of Gastroenterology and Hepatology, King Abdulaziz National Guard Hospital, Ahsa 36428, Saudi Arabia
- Internal Medicine, Zamzam University College, Khartoum 11113, Sudan
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2
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Terasawa M, Imamura H, Allard MA, Pietrasz D, Ciacio O, Pittau G, Salloum C, Sa Cunha A, Cherqui D, Adam R, Azoulay D, Saiura A, Vibert E, Golse N. Intraoperative indocyanine green fluorescence imaging to predict early hepatic arterial complications after liver transplantation. Liver Transpl 2024; 30:805-815. [PMID: 38466885 DOI: 10.1097/lvt.0000000000000355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 02/19/2024] [Indexed: 03/13/2024]
Abstract
The purpose of this study was to propose an innovative intraoperative criterion in a liver transplantation setting that would judge arterial flow abnormality that may lead to early hepatic arterial occlusion, that is, thrombosis or stenosis, when left untreated and to carry out reanastomosis. After liver graft implantation, and after ensuring that there is no abnormality on the Doppler ultrasound (qualitative and quantitative assessment), we intraoperatively injected indocyanine green dye (0.01 mg/Kg), and we quantified the fluorescence signal at the graft pedicle using ImageJ software. From the obtained images of 89 adult patients transplanted in our center between September 2017 and April 2019, we constructed fluorescence intensity curves of the hepatic arterial signal and examined their relationship with the occurrence of early hepatic arterial occlusion (thrombosis or stenosis). Early hepatic arterial occlusion occurred in 7 patients (7.8%), including 3 thrombosis and 4 stenosis. Among various parameters of the flow intensity curve analyzed, the ratio of peak to plateau fluorescence intensity and the jagged wave pattern at the plateau phase were closely associated with this dreaded event. By combining the ratio of peak to plateau at 0.275 and a jagged wave, we best predicted the occurrence of early hepatic arterial occlusion and thrombosis, with sensitivity/specificity of 0.86/0.98 and 1.00/0.94, respectively. Through a simple composite parameter, the indocyanine green fluorescence imaging system is an additional and promising intraoperative modality for identifying recipients of transplant at high risk of developing early hepatic arterial occlusion. This tool could assist the surgeon in the decision to redo the anastomosis despite normal Doppler ultrasonography.
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Affiliation(s)
- Muga Terasawa
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Hiroshi Imamura
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Marc Antoine Allard
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France
- Inserm, Université Paris-Saclay, Physiopathogénèse et traitement des maladies du foie, FHU Hepatinov, Villejuif, France
| | - Daniel Pietrasz
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France
- Inserm, Université Paris-Saclay, Physiopathogénèse et traitement des maladies du foie, FHU Hepatinov, Villejuif, France
| | - Oriana Ciacio
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France
| | - Gabriella Pittau
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France
| | - Chady Salloum
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France
| | - Antonio Sa Cunha
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France
- Inserm, Université Paris-Saclay, Physiopathogénèse et traitement des maladies du foie, FHU Hepatinov, Villejuif, France
| | - Daniel Cherqui
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France
- Inserm, Université Paris-Saclay, Physiopathogénèse et traitement des maladies du foie, FHU Hepatinov, Villejuif, France
| | - René Adam
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France
| | - Daniel Azoulay
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France
- Inserm, Université Paris-Saclay, Physiopathogénèse et traitement des maladies du foie, FHU Hepatinov, Villejuif, France
| | - Akio Saiura
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Eric Vibert
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France
- Inserm, Université Paris-Saclay, Physiopathogénèse et traitement des maladies du foie, FHU Hepatinov, Villejuif, France
| | - Nicolas Golse
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France
- Inserm, Université Paris-Saclay, Physiopathogénèse et traitement des maladies du foie, FHU Hepatinov, Villejuif, France
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Kumar V, Gautam V, Agarwal S, Pandey V, Goyal S, Nasa V, Singh SA, Al-Thihli K, Al-Murshedi F, Al Hashmi N, Al Rawahi Y, Al-Bahlani AQ, Al Said K, Gupta S. Domino liver transplantation for maple syrup urine disease in children: A single-center case series. Pediatr Transplant 2023; 27:e14603. [PMID: 37658594 DOI: 10.1111/petr.14603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 07/20/2023] [Accepted: 08/25/2023] [Indexed: 09/03/2023]
Abstract
BACKGROUND Domino liver transplant (DLT) represents another type of liver donor to expand the donor pool. Recent reports of successful DLT in children with maple syrup urine disease (MSUD) show promising long-term outcomes. METHODS It was a retrospective study. All children with MSUD were paired with either recipients with end-stage liver disease (ESLD) or non-MSUD metabolic disease. Each pair underwent simultaneous liver transplant (LT), where the MSUD recipient received the graft from a living-related donor and the liver explanted from the MSUD donor was transplanted to the respective paired domino recipient. We report our experience regarding the techniques and outcomes of DLT at our center. RESULTS Eleven children with MSUD and 12 respective DLT recipients were enrolled, one of which was domino split-liver transplantation. DLT recipients included seven ESLD, two propionic acidemia (PA), one glycogen storage disease(GSD) type-1, one GSD type-3, and one Citrullinemia. Post-LT ICU and hospital stays were comparable (p > .05). Patient and graft survival was 100% and 66.6% in the MSUD group and DLT recipients at a mean follow-up of 13.5 and 15 months. There was no death in the MSUD group as compared to four in the DLT group. The amino acid levels rapidly normalized after the LT in the children with MSUD and they tolerated the normal unrestricted diet. No vascular, biliary, or graft-related complications were seen in the post-transplant period. No occurrence of MSUD was noted in DLT recipients. CONCLUSION DLTs have excellent post-surgical outcomes. DLT should be strongly considered and adopted by transplant programs worldwide to circumvent organ shortage.
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Affiliation(s)
- Vikram Kumar
- Department of Pediatric Hepatology, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, New Delhi, India
| | - Vipul Gautam
- Department of Pediatric Hepatology, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, New Delhi, India
| | - Shaleen Agarwal
- Department of Liver Transplant Surgery, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, New Delhi, India
| | - Vijaykant Pandey
- Department of Anesthesiology, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, New Delhi, India
| | - Sumit Goyal
- Department of Anesthesiology, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, New Delhi, India
| | - Vaibhav Nasa
- Department of Anesthesiology, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, New Delhi, India
| | - Shweta A Singh
- Department of Anesthesiology, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, New Delhi, India
| | - Khalid Al-Thihli
- Genetic and Developmental Medicine Clinic, Department of Genetics, Sultan Qaboos University Hospital, Muscat, Oman
| | - Fathiya Al-Murshedi
- Genetic and Developmental Medicine Clinic, Department of Genetics, Sultan Qaboos University Hospital, Muscat, Oman
| | | | - Yusriya Al Rawahi
- Department of Child Health, Sultan Qaboos University Hospital, Muscat, Oman
| | | | - Khoula Al Said
- Department of Pediatrics, The Royal Hospital, Muscat, Oman
| | - Subhash Gupta
- Department of Liver Transplant Surgery, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, New Delhi, India
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Yamamoto H, Sambommatsu Y, Ishii M, Shimata K, Isono K, Honda M, Sugawara Y, Inomata Y, Hibi T. Surgical Outcomes of Domino Liver Transplantation Using Grafts From Living Donors With Familial Amyloid Polyneuropathy. Liver Transpl 2022; 28:603-614. [PMID: 34989109 DOI: 10.1002/lt.26401] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 11/29/2021] [Accepted: 12/19/2021] [Indexed: 01/13/2023]
Abstract
Domino liver transplantation (DLT) using grafts from donors with familial amyloid polyneuropathy is an acceptable procedure for expanding the donor pool. The vascular and biliary reconstructions in living donor DLT (LDDLT) are technically demanding, and data on the short-term and long-term surgical outcomes of domino donors and recipients in LDDLT are limited. In this study, we identified 25 domino recipients from our liver transplantation program (1999-2018), analyzed the vascular and biliary reconstructions performed, and evaluated the surgical outcomes, including graft survival. Piggyback technique was adopted in all 25 domino donors. The only surgical complication in domino donors was hepatic vein (HV) stenosis with an incidence rate of 4%. In 22 domino recipients, right HV and middle/left HV were reconstructed separately. A total of 10 recipients had 2 arteries anastomosed, and 18 underwent duct-to-duct biliary anastomosis. HV stenosis and biliary stricture had incidence rates of 8% and 24%, respectively, in the recipients, but none of them developed hepatic artery thrombosis. The 1-year and 5-year graft survival rates were 100% each in the domino donors, and 84.0% and 67.3% in the domino recipients, respectively. In conclusion, LDDLT has acceptable outcomes without increasing the operative risk in donors despite the demanding surgical technique involved.
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Affiliation(s)
- Hidekazu Yamamoto
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Yuzuru Sambommatsu
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Masatsugu Ishii
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Keita Shimata
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Kaori Isono
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Masaki Honda
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Yasuhiko Sugawara
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | | | - Taizo Hibi
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
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Raghu VK, Carr-Boyd PD, Squires JE, Vockley J, Goldaracena N, Mazariegos GV. Domino transplantation for pediatric liver recipients: Obstacles, challenges, and successes. Pediatr Transplant 2021; 25:e14114. [PMID: 34448327 PMCID: PMC9759994 DOI: 10.1111/petr.14114] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 06/23/2021] [Accepted: 07/27/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND Domino liver transplantation aims to address the need to increase the liver donor supply. In a domino liver transplant, the domino recipient receives the explanted liver from the recipient of a traditional liver transplant. The domino donor typically requires liver transplant to correct a metabolic disorder; the explanted liver thus has a single gene defect but otherwise normal structure and function. METHODS In this review, we detail the history of domino liver transplantation, appropriate domino donor indications, the technical advances to the surgical approach, current outcomes, and future opportunities. RESULTS Development of de novo disease in the domino recipient has relegated adult domino liver transplant to be considered a source of marginal donor livers. However, pediatric domino liver transplant has leveraged certain metabolic disorders, especially maple syrup urine disease, in which the liver enzyme deficiency can be compensated by the systemic presence of sufficient enzyme. Advances in the surgical aspects of assuring adequate length of vasculature have improved the safety of the procedure in both domino donors and recipients. CONCLUSIONS Pediatric domino liver transplant utilizing domino donors with specific metabolic liver diseases should be considered a viable live donor option for children awaiting liver transplant.
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Affiliation(s)
- Vikram K. Raghu
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, UPMC Children’s Hospital Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Peter D. Carr-Boyd
- Hillman Center for Pediatric Transplantation, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - James E. Squires
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, UPMC Children’s Hospital Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Jerry Vockley
- Division of Medical Genetics, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Nicolas Goldaracena
- Division of Transplant Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, Virginia, USA
| | - George V. Mazariegos
- Hillman Center for Pediatric Transplantation, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
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6
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Pluta KD, Ciezkowska M, Wisniewska M, Wencel A, Pijanowska DG. Cell-based clinical and experimental methods for assisting the function of impaired livers – Present and future of liver support systems. Biocybern Biomed Eng 2021. [DOI: 10.1016/j.bbe.2021.06.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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7
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Gad El-Hak HN, Abdelrazek HMA, Zeidan DW, Almallah AA, Khaled HE. Assessment of changes in the liver of pregnant female rats and their fetuses following monosodium glutamate administration. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2021; 28:44432-44441. [PMID: 33847887 DOI: 10.1007/s11356-021-13557-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 03/16/2021] [Indexed: 06/12/2023]
Abstract
Monosodium glutamate (MSG) is a common flavor enhancer and stabilizer for ready-made or packaged foods. This research investigated the impact of MSG on the maternal and fetal liver. The present study was carried out on sixteen mature female Albino rats and eight male rats of reproductive age. The control group was dissected on day 20 of gestation. MSG group was administrated MSG daily at a dosage of 1 g/5 mL/kg body weight from day 0 to day 20 of gestation. The liver function and lipid profile of the control and treated mothers were investigated in the blood sera. The levels of nitric oxide (NO), tumor necrosis factor (TNF-α), superoxide dismutase (SOD), and reduced glutathione (GSH) activities in the liver homogenate of maternal and fetal tissue were assayed, in addition to histopathological, histochemical and immunohistochemical studies were done to the liver tissue. The activities of liver functions and lipid profile significantly altered in the treated mothers with MSG. MSG significantly reduced the SOD and reduced GSH activities in addition to the elevated TNF-α and NO in liver tissue of pregnant mothers and their fetuses. Severe histopathological alterations were observed in both maternal and fetal liver tissues of MSG-treated groups. Moreover, histochemical observations showed a reduction of total polysaccharides in the liver of pregnant rats and fetuses. A significant increase in the percentage area of positive immunoreaction for caspase 3 was observed in the liver of treated rats with MSG compared to the liver of the control. The liver of fetuses treated with MSG revealed an alteration like their mother. This study showed that during the gestational period MSG exposure resulted in several biochemical, histological, and histochemical changes in the maternal and fetal liver tissues which emphasize the toxic effect of MSG.
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Affiliation(s)
- Heba N Gad El-Hak
- Zoology Department, Faculty of Sciences, Suez Canal University, Ismailia, Egypt.
| | - Heba M A Abdelrazek
- Department of Physiology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt
| | - Dalia W Zeidan
- Department of Home and Economics, Nutrition and Food Science Branch, Faculty of Education, Suez Canal University, Ismailia, Egypt
| | - Amani A Almallah
- Department of Anatomy and Embryology, Faculty of Medicine, Suez University, Ismailia, Egypt
| | - Howayda E Khaled
- Zoology Department, Faculty of Sciences, Suez University, Ismailia, Egypt
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Lerut J, Foguenne M, Lai Q, de Ville de Goyet J. Domino-liver transplantation: toward a safer and simpler technique in both donor and recipient. Updates Surg 2021; 73:223-232. [PMID: 32965591 PMCID: PMC7889565 DOI: 10.1007/s13304-020-00886-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 09/04/2020] [Indexed: 11/29/2022]
Abstract
Domino-liver transplantation represents a rare chance to expand the donor liver pool. Fear of putting both donor and recipient at disadvantage has meant that the procedure has not been applied universally. A modification of the original technique which allows both safe procurement of the graft as well as safe implantation of the reconstructed graft in the domino-graft recipient using a 180° rotated, adequately trimmed, free iliaco-caval venous graft is described in detail.
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Affiliation(s)
- Jan Lerut
- Institute for Experimental and Clinical Research (IREC), Université Catholique de Louvain (UCL), Avenue Hippocrate 55, 1200, Brussels, Belgium.
| | - Maxime Foguenne
- Institute for Experimental and Clinical Research (IREC), Université Catholique de Louvain (UCL), Avenue Hippocrate 55, 1200, Brussels, Belgium
| | - Quirino Lai
- Liver Transplant Program, Sapienza University of Rome, Rome, Italy.
| | - Jean de Ville de Goyet
- University Pittsburgh Medical Center (UPMC-Italy) at the ISMETT (Istituto Mediterraneo for Trapianto e Terapie ad Alta Specializzazione), IRCCS, Palermo, Italy
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9
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Dousse D, Vibert E, Nicolas Q, Terasawa M, Cano L, Allard MA, Salloum C, Ciacio O, Pittau G, Sa Cunha A, Cherqui D, Adam R, Samuel D, Vignon-Clementel I, Golse N. Indocyanine Green Fluorescence Imaging to Predict Graft Survival After Orthotopic Liver Transplantation: A Pilot Study. Liver Transpl 2020; 26:1263-1274. [PMID: 32402148 DOI: 10.1002/lt.25796] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 03/23/2020] [Accepted: 04/25/2020] [Indexed: 02/07/2023]
Abstract
The incidence of primary nonfunction (PNF) after liver transplantation (LT) remains a major concern with the increasing use of marginal grafts. Indocyanine green (ICG) fluorescence is an imaging technique used in hepatobiliary surgery and LT. Because few early predictors are available, we aimed to quantify in real time the fluorescence of grafts during LT to predict 3-month survival. After graft revascularization, ICG was intravenously injected, and then the fluorescence of the graft was captured with a near infrared camera and postoperatively quantified. A multiparametric modeling of the parenchymal fluorescence intensity (FI) curve was proposed, and a predictive model of graft survival was tested. Between July 2017 and May 2019, 76 LTs were performed, among which 6 recipients underwent retransplantation. No adverse effects of ICG injection were observed. The parameter a150 (temporal course of FI) was significantly higher in the re-LT group (0.022 seconds-1 (0.0011-0.059) versus 0.012 seconds-1 (0.0001-0.054); P = 0.01). This parameter was the only independent predictive factor of graft survival at 3 months (OR, 2.4; 95% CI, 1.05-5.50; P = 0.04). The best cutoff for the parameter a150 (0.0155 seconds-1 ) predicted the graft survival at 3 months with a sensitivity (Se) of 83.3% and a specificity (Spe) of 78.6% (area under the curve, 0.82; 95% CI, 0.67-0.98; P = 0.01). Quantitative assessment of intraoperative ICG fluorescence on the graft was feasible to predict graft survival at 3 months with a good Se and Spe. Further prospective studies should be undertaken to validate these results over larger cohorts and evaluate the clinical impact of this tool.
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Affiliation(s)
- Damien Dousse
- Department of Hepato-Biliary and Liver Transplant, AP-HP Paul Brousse Hospital, Centre Hépato-Biliaire, Villejuif, France
- Unit 1193, INSERM, Villejuif, France
- Department of Digestive Surgery, Rangueil University Hospital, Toulouse, France
| | - Eric Vibert
- Department of Hepato-Biliary and Liver Transplant, AP-HP Paul Brousse Hospital, Centre Hépato-Biliaire, Villejuif, France
- Unit 1193, INSERM, Villejuif, France
| | | | - Muga Terasawa
- Department of Hepato-Biliary and Liver Transplant, AP-HP Paul Brousse Hospital, Centre Hépato-Biliaire, Villejuif, France
| | | | - Marc-Antoine Allard
- Department of Hepato-Biliary and Liver Transplant, AP-HP Paul Brousse Hospital, Centre Hépato-Biliaire, Villejuif, France
- Unit 1193, INSERM, Villejuif, France
| | - Chady Salloum
- Department of Hepato-Biliary and Liver Transplant, AP-HP Paul Brousse Hospital, Centre Hépato-Biliaire, Villejuif, France
| | - Oriana Ciacio
- Department of Hepato-Biliary and Liver Transplant, AP-HP Paul Brousse Hospital, Centre Hépato-Biliaire, Villejuif, France
| | - Gabriella Pittau
- Department of Hepato-Biliary and Liver Transplant, AP-HP Paul Brousse Hospital, Centre Hépato-Biliaire, Villejuif, France
| | - Antonio Sa Cunha
- Department of Hepato-Biliary and Liver Transplant, AP-HP Paul Brousse Hospital, Centre Hépato-Biliaire, Villejuif, France
- Unit 1193, INSERM, Villejuif, France
| | - Daniel Cherqui
- Department of Hepato-Biliary and Liver Transplant, AP-HP Paul Brousse Hospital, Centre Hépato-Biliaire, Villejuif, France
- Unit 1193, INSERM, Villejuif, France
| | - René Adam
- Department of Hepato-Biliary and Liver Transplant, AP-HP Paul Brousse Hospital, Centre Hépato-Biliaire, Villejuif, France
- Unit 985, INSERM, Villejuif, France
| | - Didier Samuel
- Department of Hepato-Biliary and Liver Transplant, AP-HP Paul Brousse Hospital, Centre Hépato-Biliaire, Villejuif, France
- Unit 1193, INSERM, Villejuif, France
| | | | - Nicolas Golse
- Department of Hepato-Biliary and Liver Transplant, AP-HP Paul Brousse Hospital, Centre Hépato-Biliaire, Villejuif, France
- Unit 1193, INSERM, Villejuif, France
- Inria, Paris, France
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10
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Arterial Lactate Concentration at the End of Liver Transplantation Is an Early Predictor of Primary Graft Dysfunction. Ann Surg 2020; 270:131-138. [PMID: 29509585 DOI: 10.1097/sla.0000000000002726] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Although many prognostic factors of primary graft dysfunction after liver transplantation (LT) are available, it remains difficult to predict failure in a given recipient. OBJECTIVE We aimed to determine whether the intraoperative assay of arterial lactate concentration at the end of LT (LCEOT) might constitute a reliable biological test to predict early outcomes [primary nonfunction (PNF), early graft dysfunction (EAD)]. METHODS We reviewed data from a prospective database in a single center concerning patients transplanted between January 2015 and December 2016 (n = 296). RESULTS There was no statistical imbalance between the training (year 2015) and validation groups (year 2016) for epidemiological and perioperative feature. Ten patients (3.4%) presented with PNF, and EAD occurred in 62 patients (20.9%); 9 patients died before postoperative day (POD) 90. LCEOT ≥5 mmol/L was the best cut-off point to predict PNF (Se=83.3%, SP=74.3%, positive likelihood ratio (LR+)=3.65, negative likelihood ratio (LR-)=0.25, diagnostic odds ratio (DOR)=14.44) and was predictive of PNF (P = 0.02), EAD (P = 0.05), and death ≤ POD90 (P = 0.06). Added to the validated BAR-score, LCEOT improved its predictive value regarding POD 90 survival with a better AUC (0.87) than BAR score (0.74). The predictive value of LCEOT was confirmed in the validation cohort. CONCLUSION As a reflection of both hypoperfusion and tissue damage, the assay of arterial LCEOT ≥5 mmol/L appears to be a strong predictor of early graft outcomes and may be used as an endpoint in studies assessing the impact of perioperative management. Its accessibility and low cost could impose it as a reliable parameter to anticipate postoperative management and help clinicians for decision-making in the first PODs.
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11
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Celik N, Kelly B, Soltys K, Squires JE, Vockley J, Shellmer DA, Strauss K, McKiernan P, Ganoza A, Sindhi R, Bond G, Mazariegos G, Khanna A. Technique and outcome of domino liver transplantation from patients with maple syrup urine disease: Expanding the donor pool for live donor liver transplantation. Clin Transplant 2019; 33:e13721. [PMID: 31556146 DOI: 10.1111/ctr.13721] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 08/22/2019] [Accepted: 08/31/2019] [Indexed: 01/26/2023]
Abstract
AIM/BACKGROUND Domino liver transplantation (DLT) using liver allografts from patients with metabolic disorders enhances organ utilization. Short- and long-term course and outcome of these patients can impact the decision to offer this procedure to patients, especially those with diseases that can potentially be cured with liver transplant. We reviewed the outcomes of DLT from maple syrup urine disease (MSUD) patients in our large academic pediatric and adult transplant program. METHODS All patients receiving DLT were analyzed retrospectively with a minimum of one-year follow-up period for patient and donor characteristics, early and late postoperative complications and patient and graft survival with their MSUD donors in terms of age, weight, MELD/PELD scores, cold ischemia time, postoperative leucine levels, and peak ALT (alanine aminotransferase) levels during the first 48 postoperative hours. RESULTS Between 2006 and May 2019, 21 patients underwent domino liver transplantation with live donor allografts from MSUD patients. Four patients transplanted for different metabolic diseases are focus of a separate report. Seventeen patients with minimum one-year follow-up period are reported herein. The indications were primary sclerosing cholangitis (PSC, n = 4), congenital hepatic fibrosis (CHF, n = 2), alpha-1 antitrypsin deficiency (A-1 ATD, n = 2), progressive familial intrahepatic cholestasis (PFIC, n = 2), cystic fibrosis (n = 1), primary biliary cirrhosis (PBC, n = 1), neonatal hepatitis (n = 1), embryonal sarcoma (n = 1), Caroli disease (n = 1), hepatocellular carcinoma (HCC, n = 1), and chronic rejection after liver transplantations for PSC (n = 1). All patients and grafts survived at median follow-up of 6.4 years (range 1.2-12.9 years). Median domino recipient age was 16.2 years (range 0.6-64.6 years) and median MSUD recipient age was 17.6 years (range 4.8-32.1 years). There were no vascular complications during the early postoperative period, one patient had portal vein thrombosis 3 years after DLT and a meso-Rex bypass was successfully performed. Small for size syndrome (SFSS) occurred in reduced left lobe DLT recipient and was managed successfully with conservative management. Biliary stricture developed in 2 patients and was resolved by stenting. Comparison between DLT and MSUD recipients' peak postoperative ALT results and PELD/MELD scores showed lower levels in DLT group (P-value <.05). CONCLUSIONS Patient and graft survival in DLT from MSUD donors was excellent at short- and long-term follow-up. Metabolic functions have been normal in all recipients on a normal unrestricted protein diet. Ischemia preservation injury based on peak ALT was significantly decreased in DLT recipients. Domino transplantation from pediatric and adult recipients with selected metabolic diseases should be increasingly considered as an excellent option and alternative to deceased donor transplantation, thereby expanding the living donor pool. This, to date, is the largest world experience in DLT utilizing livers from patients with MSUD.
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Affiliation(s)
- Neslihan Celik
- Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC, Thomas E. Starzl Transplant Institute, Pittsburgh, PA, USA
| | - Beau Kelly
- DCI Donor Services Inc, Sacramento, CA, USA
| | - Kyle Soltys
- Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC, Thomas E. Starzl Transplant Institute, Pittsburgh, PA, USA
| | - James E Squires
- Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC, Thomas E. Starzl Transplant Institute, Pittsburgh, PA, USA
| | - Jerry Vockley
- Center for Rare Disease Therapy, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA
| | - Diana A Shellmer
- Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC, Thomas E. Starzl Transplant Institute, Pittsburgh, PA, USA
| | - Kevin Strauss
- Pediatric Hepatology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.,Clinic for Special Children, Strasburg, PA, USA
| | - Patrick McKiernan
- Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC, Thomas E. Starzl Transplant Institute, Pittsburgh, PA, USA
| | - Armando Ganoza
- Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC, Thomas E. Starzl Transplant Institute, Pittsburgh, PA, USA
| | - Rakesh Sindhi
- Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC, Thomas E. Starzl Transplant Institute, Pittsburgh, PA, USA
| | - Geoffrey Bond
- Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC, Thomas E. Starzl Transplant Institute, Pittsburgh, PA, USA
| | - George Mazariegos
- Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC, Thomas E. Starzl Transplant Institute, Pittsburgh, PA, USA
| | - Ajai Khanna
- Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC, Thomas E. Starzl Transplant Institute, Pittsburgh, PA, USA
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12
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Celik N, Squires JE, Soltys K, Vockley J, Shellmer DA, Chang W, Strauss K, McKiernan P, Ganoza A, Sindhi R, Bond G, Mazariegos G, Khanna A. Domino liver transplantation for select metabolic disorders: Expanding the living donor pool. JIMD Rep 2019; 48:83-89. [PMID: 31392117 PMCID: PMC6606984 DOI: 10.1002/jmd2.12053] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Revised: 05/17/2019] [Accepted: 05/21/2019] [Indexed: 01/20/2023] Open
Abstract
Domino liver transplantation (DLT) involves transplanting liver from a patient with metabolic disease into a patient with end-stage liver disease with the expectation that the recipient will not develop the metabolic syndrome or the recurrent syndrome will have minimal affect. The domino donor gets a deceased donor or a segment of live-donor liver through the deceased donor organ allocation system. Waitlist mortality for the domino recipient exceeds morbidity associated with getting the donor disease. Between 2015 and 2017, four patients with three metabolic disorders at UPMC Children's Hospital of Pittsburgh underwent DLT with domino allografts from maple syrup urine disease (MSUD) patients. These included patients with propionic acidemia (PA) (n = 1), Crigler-Najjar (CN) syndrome type-1 (n = 2), and carbamoyl phosphate synthetase deficiency (CPSD) (n = 1). Mean follow-up was 1.6 years (range 1.1-2.1 years). Total bilirubin levels normalized postoperatively in both CN patients and they maintain normal allograft function. The PA patient had normal to minimal elevations of isoleucine and leucine, and no other abnormalities on low protein diet supplemented with a low methionine and valine free formula. No metabolic crises have occurred. The patient with CPSD takes normal baby food. No elevation in ammonia levels have been observed in any of the patients. DLT for a select group of metabolic diseases alleviated the recipients of their metabolic defect with minimal evidence of transferrable-branched chain amino acid elevations or clinical MSUD despite increased protein intake. DLT using allografts with MSUD expands the live donor liver pool and should be considered for select metabolic diseases that may have a different enzymatic deficiency.
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Affiliation(s)
- Neslihan Celik
- Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMCThomas E. Starzl Transplantation Institute, University of Pittsburgh School of MedicinePittsburghPennsylvania
| | - James E. Squires
- Pediatric HepatologyChildren's Hospital of Pittsburgh of UPMCPittsburghPennsylvania
| | - Kyle Soltys
- Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMCThomas E. Starzl Transplantation Institute, University of Pittsburgh School of MedicinePittsburghPennsylvania
| | - Jerry Vockley
- Division of Medical GeneticsUniversity of Pittsburgh School of Medicine, Center for Rare Disease Therapy, Children's Hospital of Pittsburgh of UPMCPittsburghPennsylvania
| | - Diana A. Shellmer
- Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMCThomas E. Starzl Transplantation Institute, University of Pittsburgh School of MedicinePittsburghPennsylvania
| | - Wonbae Chang
- Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMCThomas E. Starzl Transplantation Institute, University of Pittsburgh School of MedicinePittsburghPennsylvania
| | - Kevin Strauss
- Division of Medical GeneticsUniversity of Pittsburgh School of Medicine, Center for Rare Disease Therapy, Children's Hospital of Pittsburgh of UPMCPittsburghPennsylvania
| | - Patrick McKiernan
- Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMCThomas E. Starzl Transplantation Institute, University of Pittsburgh School of MedicinePittsburghPennsylvania
| | - Armando Ganoza
- Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMCThomas E. Starzl Transplantation Institute, University of Pittsburgh School of MedicinePittsburghPennsylvania
| | - Rakesh Sindhi
- Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMCThomas E. Starzl Transplantation Institute, University of Pittsburgh School of MedicinePittsburghPennsylvania
| | - Geoffrey Bond
- Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMCThomas E. Starzl Transplantation Institute, University of Pittsburgh School of MedicinePittsburghPennsylvania
| | - George Mazariegos
- Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMCThomas E. Starzl Transplantation Institute, University of Pittsburgh School of MedicinePittsburghPennsylvania
| | - Ajai Khanna
- Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMCThomas E. Starzl Transplantation Institute, University of Pittsburgh School of MedicinePittsburghPennsylvania
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13
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Santopaolo F, Lenci I, Bosa A, Angelico M, Milana M, Baiocchi L. Domino Liver Transplantation: Where are we Now? Rev Recent Clin Trials 2019; 14:183-188. [PMID: 30894112 DOI: 10.2174/1574887114666190320123824] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Revised: 03/04/2019] [Accepted: 03/15/2019] [Indexed: 11/22/2022]
Abstract
BACKGROUND Domino transplant occurs when a recipient explanted graft is used for a second recipient. INTRODUCTION The first experience came from thoracic surgery by the observation that many patients during heart-lung transplantation actually showed a functional heart that could be employed in other subjects with a good result. RESULTS This concept was then extended to the field of liver transplantation. At present, some patients transplanted for an inborn metabolic disease may be considered as excellent domino liver donors. CONCLUSION The results, limitations, clinical challenges and the donor and recipient features of domino liver transplantation are discussed in this manuscript.
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Affiliation(s)
- Francesco Santopaolo
- Unita Operativa di Epatologia, Policlinico Universitario di "Tor Vergata"; Viale Oxford 81, 00133 Rome, Italy
| | - Ilaria Lenci
- Unita Operativa di Epatologia, Policlinico Universitario di "Tor Vergata"; Viale Oxford 81, 00133 Rome, Italy
| | - Alessandra Bosa
- Unita Operativa di Epatologia, Policlinico Universitario di "Tor Vergata"; Viale Oxford 81, 00133 Rome, Italy
| | - Mario Angelico
- Unita Operativa di Epatologia, Policlinico Universitario di "Tor Vergata"; Viale Oxford 81, 00133 Rome, Italy
| | - Martina Milana
- Unita Operativa di Epatologia, Policlinico Universitario di "Tor Vergata"; Viale Oxford 81, 00133 Rome, Italy
| | - Leonardo Baiocchi
- Unita Operativa di Epatologia, Policlinico Universitario di "Tor Vergata"; Viale Oxford 81, 00133 Rome, Italy
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14
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Is Routine Intraoperative Contrast-Enhanced Ultrasonography Useful During Whole Liver Transplantation? World J Surg 2017; 42:1523-1535. [DOI: 10.1007/s00268-017-4295-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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15
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Barroso FA, Judge DP, Ebede B, Li H, Stewart M, Amass L, Sultan MB. Long-term safety and efficacy of tafamidis for the treatment of hereditary transthyretin amyloid polyneuropathy: results up to 6 years. Amyloid 2017; 24:194-204. [PMID: 28758793 DOI: 10.1080/13506129.2017.1357545] [Citation(s) in RCA: 85] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
BACKGROUND The objective of the present study was to evaluate the long-term safety and efficacy of tafamidis in treating hereditary transthyretin amyloid polyneuropathy. METHODS A prospectively planned interim analysis was conducted on an on-going, phase III, open-label extension study following an 18-month, randomized, controlled study and 12-month, open-label extension study in ATTRV30M patients and a single-arm, open-label study in non-ATTRV30M patients. Thirty-seven ATTRV30M patients received placebo for 18 months, then switched to tafamidis and 38 ATTRV30M patients and 18 non-ATTRV30M patients continuously received tafamidis from day 1, up to 6 years. RESULTS Long-term tafamidis was associated with a favourable safety/tolerability profile, without any unexpected adverse events. Patients initiating tafamidis at the start of the randomized study had less polyneuropathy progression versus those switching to tafamidis following 18 months of placebo and were less likely to progress to the next ambulatory stage after up to 6 years follow-up. In the patients who switched from placebo to tafamidis, polyneuropathy progression and deterioration in quality of life slowed significantly during long-term tafamidis treatment as compared with the previous placebo treatment. In non-ATTRV30M patients, some polyneuropathy progression was observed across all efficacy measures. CONCLUSIONS These data provide evidence for the long-term (up to 6 years) safety and efficacy of tafamidis.ClinicalTrials.gov: NCT00925002.
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Affiliation(s)
- Fabio A Barroso
- a Department of Neurology , Institute for Neurological Research Raúl Carrea, FLENI , Buenos Aires , Argentina
| | - Daniel P Judge
- b Johns Hopkins University Center for Inherited Heart Disease , Baltimore , MD , USA
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16
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Golse N, Bucur PO, Ciacio O, Pittau G, Sa Cunha A, Adam R, Castaing D, Antonini T, Coilly A, Samuel D, Cherqui D, Vibert E. A new definition of sarcopenia in patients with cirrhosis undergoing liver transplantation. Liver Transpl 2017; 23:143-154. [PMID: 28061014 DOI: 10.1002/lt.24671] [Citation(s) in RCA: 126] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Revised: 09/13/2016] [Accepted: 10/18/2016] [Indexed: 02/07/2023]
Abstract
Although sarcopenia is a common complication of cirrhosis, its diagnosis remains nonconsensual: computed tomography (CT) scan determinations vary and no cutoff values have been established in cirrhotic populations undergoing liver transplantation (LT). Our aim was to compare the accuracy of the most widely used measurement techniques and to establish useful cutoffs in the setting of LT. From the 440 patients transplanted between January 2008 and May 2011 in our tertiary center, we selected 256 patients with cirrhosis for whom a recent CT scan was available during the 4 months prior to LT. We measured different muscle indexes: psoas muscle area (PMA), PMA normalized by height or body surface area (BSA), and the third lumbar vertebra skeletal muscle index (L3SMI). Receiver operating characteristic curves were evaluated and prognostic factors for post-LT 1-year survival were then analyzed. PMA offered better accuracy (area under the curve [AUC] = 0.753) than L3SMI (AUC = 0.707) and PMA/BSA (AUC = 0.732), and the same accuracy as PMA/squared height. So, for its accuracy and simplicity of use, the PMA index was used for the remainder of the analysis and to define sarcopenia. In men, the better cutoff value for PMA was 1561 mm2 (Se = 94%, Sp = 57%), whereas in women, it was 1464 mm2 (Se = 52%, Sp = 91%). A PMA lower than these values defined sarcopenia in patients with cirrhosis awaiting LT. One- and 5-year overall survival rates were significantly poorer in the sarcopenic group (n = 57) than in the nonsarcopenic group (n = 199), at 59% versus 94% and 54% versus 80%, respectively (P < 0.001). In conclusion, pre-LT PMA is a simple tool to assess sarcopenia. We established sex-specific cutoff values (1561 mm2 in men, 1464 mm2 in women) in a cirrhotic population and showed that 1-year survival was significantly poorer in sarcopenic patients. Liver Transplantation 23 143-154 2017 AASLD.
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Affiliation(s)
- Nicolas Golse
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France.,Université Paris-Sud, Villejuif, France
| | - Petru Octav Bucur
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France
| | - Oriana Ciacio
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France
| | - Gabriella Pittau
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France
| | - Antonio Sa Cunha
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France.,Université Paris-Sud, Villejuif, France.,Unit 1193
| | - René Adam
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France.,Université Paris-Sud, Villejuif, France.,Unit 776, INSERM, Villejuif, France
| | - Denis Castaing
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France.,Université Paris-Sud, Villejuif, France.,Unit 1193
| | - Teresa Antonini
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France
| | - Audrey Coilly
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France
| | - Didier Samuel
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France.,Université Paris-Sud, Villejuif, France.,Unit 1193
| | - Daniel Cherqui
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France.,Université Paris-Sud, Villejuif, France.,Unit 1193
| | - Eric Vibert
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France.,Université Paris-Sud, Villejuif, France.,Unit 1193
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17
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Rajakannu M, Awad S, Ciacio O, Pittau G, Adam R, Cunha AS, Castaing D, Samuel D, Lewin M, Cherqui D, Vibert E. Intention-to-treat analysis of percutaneous endovascular treatment of hepatic artery stenosis after orthotopic liver transplantation. Liver Transpl 2016; 22:923-33. [PMID: 27097277 DOI: 10.1002/lt.24468] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2015] [Accepted: 03/16/2016] [Indexed: 02/06/2023]
Abstract
Hepatic artery stenosis (HAS) is a rare complication of orthotopic liver transplantation (LT). HAS could evolve into complete thrombosis and lead to graft loss, incurring significant morbidity and mortality. Even though endovascular management by percutaneous transluminal angioplasty ± stenting (PTA) is the primary treatment of HAS, its longterm impact on hepatic artery (HA) patency and graft survival remains unclear. This study aimed to evaluate longterm outcomes of PTA and to define the risk factors of treatment failure. From 2006 to 2012, 30 patients with critical HAS (>50% stenosis of HA) and treated by PTA were identified from 870 adult patients undergoing LT. Seventeen patients were diagnosed by post-LT screening, and 13 patients were symptomatic due to HAS. PTA was completed successfully in 27 (90%) patients with angioplasty plus stenting in 23 and angioplasty alone in 4. The immediate technical success rate was 90%. A major complication that was observed was arterial dissection (1 patient) which eventually necessitated retransplantation. Restenosis was observed in 10 (33%) patients. One-year, 3-year, and 5-year HA patency rates were 68%, 62.8%, and 62.8%, respectively. Overall patient survival was 93.3% at 3 years and 85.3% at 5 years. The 3-year and 5-year liver graft survival rates were 84.7% and 64.5%, respectively. No significant difference was observed in patient and graft survivals between asymptomatic and symptomatic patients after PTA. Similarly, no difference was observed between angioplasty alone and angioplasty plus stenting. In conclusion, endovascular therapy ensures a good 5-year graft survival (64.5%) and patient survival (85.3%) in patients with critical HAS by maintaining HA patency with a low risk of serious morbidity (3.3%). Liver Transplantation 22 923-933 2016 AASLD.
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Affiliation(s)
- Muthukumarassamy Rajakannu
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France.,Unités Mixtes de Recherche en Santé 1193, INSERM, Villejuif, France.,Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre, France
| | - Sameh Awad
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France
| | - Oriana Ciacio
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France
| | - Gabriella Pittau
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France
| | - René Adam
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France.,Unités Mixtes de Recherche en Santé 776, INSERM, Villejuif, France.,Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre, France
| | - Antonio Sa Cunha
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France.,Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre, France
| | - Denis Castaing
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France.,Unités Mixtes de Recherche en Santé 1193, INSERM, Villejuif, France.,Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre, France
| | - Didier Samuel
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France.,Unités Mixtes de Recherche en Santé 1193, INSERM, Villejuif, France.,Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre, France
| | - Maïté Lewin
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France.,Unités Mixtes de Recherche en Santé 1193, INSERM, Villejuif, France
| | - Daniel Cherqui
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France.,Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre, France
| | - Eric Vibert
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France.,Unités Mixtes de Recherche en Santé 1193, INSERM, Villejuif, France.,Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre, France
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18
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Long-term Results of Domino Liver Transplantation for Hepatocellular Carcinoma Using the "Double Piggy-back" Technique: A 13-Year Experience. Ann Surg 2016; 262:749-56; discussion 756. [PMID: 26583662 DOI: 10.1097/sla.0000000000001446] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
OBJECTIVES The aim of this study was to evaluate the long-term outcome of liver transplantation (LT) for hepatocellular carcinoma (HCC) with Domino LT (DLT) using the "Double Piggy-back" technique. BACKGROUND DATA DLT using livers from familial amyloidotic polyneuropathy (FAP) patients is a well-described technique and useful for expanding the donor pool. However, data on long-term results for HCC are limited, particularly regarding the use of the "Double Piggy-back" technique. METHODS Between 2001 and 2014, a total of 260 patients undergoing LT for HCC were analyzed from a prospective database. Of those, 114 were submitted to DLT. Comparisons between groups were performed using propensity score matching. RESULTS Median follow-up was 34 months (1-152). Overall and disease-free 5-year survival rates for the whole population were 58% and 56%, respectively. There were 177 (68%) patients within Milan Criteria and an additional 26 (10%) within University of California San Francisco (UCSF) criteria. Patients older than 50 years were more likely to receive an FAP liver [odds ratio (OR) 1.94, confidence interval (CI) 1.02-3.69]. DLT patients had more major complications (23.7% vs 13.0%, P = 0.025). Only patients undergoing DLT presented with piggy-back syndrome (7% vs 0%, P = 0.001). After adjusting for potential confounders, DLT and cadaveric LT had a similar 5-year survival rate (59% vs 44%, respectively, P = 0.117). Thirteen patients (11.4%) evidenced FAP disease but not before 6 years after DLT. CONCLUSIONS DLT for HCC is feasible and achieves equivalent results to cadaveric LT. The benefit of expanding the donor pool must be balanced against higher morbidity and a real risk of disease transmission.
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19
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Yoshinaga T, Yazaki M, Sekijima Y, Kametani F, Miyashita K, Hachiya N, Tanaka T, Kokudo N, Higuchi K, Ikeda SI. The pathological and biochemical identification of possible seed-lesions of transmitted transthyretin amyloidosis after domino liver transplantation. JOURNAL OF PATHOLOGY CLINICAL RESEARCH 2016; 2:72-9. [PMID: 27499917 PMCID: PMC4907057 DOI: 10.1002/cjp2.36] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Accepted: 12/16/2015] [Indexed: 11/23/2022]
Abstract
The most serious issue in domino liver transplantation (DLT) using liver grafts from patients with transthyretin (TTR)‐related familial amyloid polyneuropathy (FAP) is the development of iatrogenic transmitted amyloidosis (de novo amyloidosis) in DLT‐recipients. However, little is known regarding the mechanisms of the initial stage of amyloid formation in these recipients. We detected initial lesions (possible seed‐lesions) of this iatrogenic amyloidosis in two recipients following liver grafting from FAP patients. Patient 1 underwent DLT at age 65 from an FAP patient with a Val30Met TTR variant and patient 2 received DLT from an FAP patient with a Val30Leu TTR variant at age 32. Patient 2 was started on diflunisal administration from 4 years after DLT. While neither patient had symptoms of FAP, small amyloid deposits were detected on the gastroduodenal mucosae 14 months and 12 years after DLT in patient 1 and patient 2, respectively. The amyloid was analyzed using a laser microdissection system and tandem mass spectrometry. Biochemical analysis indicated that the amyloid was composed mostly of variant TTR produced from the transplanted liver in both patients. In patient 1, wild‐type TTR amyloid was detectable in the duodenal mucosa obtained 2 years after DLT. This is the first study to successfully capture the pathological and biochemical features of initial‐stage amyloid lesions in DLT recipients. The findings clearly indicate that amyloid deposition can start by deposition of variant TTR followed by deposition of wild‐type TTR, and blocking of amyloid seed formation from variant TTR may be a key to prevent or delay the development of DLT‐associated amyloidosis.
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Affiliation(s)
- Tsuneaki Yoshinaga
- Department of Medicine (Neurology and Rheumatology) Shinshu University School of Medicine Matsumoto Japan
| | - Masahide Yazaki
- Department of Medicine (Neurology and Rheumatology)Shinshu University School of MedicineMatsumotoJapan; Department of Biological Sciences for Intractable Neurological Diseases, Institute for Biomedical Sciences, Shinshu UniversityMatsumotoJapan
| | - Yoshiki Sekijima
- Department of Medicine (Neurology and Rheumatology)Shinshu University School of MedicineMatsumotoJapan; Department of Biological Sciences for Intractable Neurological Diseases, Institute for Biomedical Sciences, Shinshu UniversityMatsumotoJapan
| | - Fuyuki Kametani
- Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science Tokyo Japan
| | - Kana Miyashita
- Department of Neurophysiology Tokyo Medical University Tokyo Japan
| | - Naomi Hachiya
- Department of Neurophysiology Tokyo Medical University Tokyo Japan
| | - Tomohiro Tanaka
- Department of Organ Transplantation Service The University of Tokyo Hospital Tokyo Japan
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of TokyoTokyoJapan; Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of TokyoTokyoJapan
| | - Keiichi Higuchi
- Department of Biological Sciences for Intractable Neurological Diseases, Institute for Biomedical Sciences, Shinshu UniversityMatsumotoJapan; Department of Aging BiologyInstitute of Pathogenesis and Disease Prevention, Shinshu University Graduate School of MedicineMatsumotoJapan
| | - Shu-Ichi Ikeda
- Department of Medicine (Neurology and Rheumatology)Shinshu University School of MedicineMatsumotoJapan; Department of Biological Sciences for Intractable Neurological Diseases, Institute for Biomedical Sciences, Shinshu UniversityMatsumotoJapan
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20
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Golse N, Bucur PO, Faitot F, Bekheit M, Pittau G, Ciacio O, Sa Cunha A, Adam R, Castaing D, Samuel D, Cherqui D, Vibert E. Spontaneous Splenorenal Shunt in Liver Transplantation: Results of Left Renal Vein Ligation Versus Renoportal Anastomosis. Transplantation 2015; 99:2576-2585. [PMID: 25989502 DOI: 10.1097/tp.0000000000000766] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Management of portal inflow to the graft in patients with spontaneous splenorenal shunts (SRS) is a matter of concern especially in case of large varices (more than 1 cm). In case of portal vein (PV) thrombosis (PVT), renoportal anastomosis (RPA) directly diverts the splanchnic and renal venous blood assuring a good portal inflow to the graft. Disconnection of the portacaval shunt by left renal vein ligation (LRVL) is another option but requires a patent PV. The indication of primary RPA rather than LRVL in patients with small native PV, especially in case of large graft, should be questioned in these complex cases of liver transplantation. METHODS From 1998 to 2012, 17 patients with RPA and 15 patients with LRVL were transplanted in our center. We compared these 2 techniques for short- and long-term results. RESULTS The rate of preliver transplantation PVT (76% vs 27%) and graft weight (1538 ± 383 g vs 1293 ± 216 g) was significantly higher in the RPA group. Renoportal anastomosis was performed in 4 cases of small but patent PV. Three-month mortality, morbidity, and massive ascitis were similar. No patient was retransplanted. One year after transplantation, PV diameter was still larger in RPA group. Three-year survival was similar (RPA: 79% vs LRVL: 53%, P = 0.1). CONCLUSIONS In cirrhotic patients transplanted with large splenorenal shunts, RPA and LRVL reach similar survivals. In case of complete PVT and failure of thrombectomy, the RPA offers satisfactory long-term results.
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Affiliation(s)
- Nicolas Golse
- 1 AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France. 2 Inserm, Unité 1193, Villejuif, F-94800, France. 3 Univ Paris-Sud, UMR-S 1193, Villejuif, F-94800, France. 4 Inserm, Unité 776, Villejuif, F-94800, France. 5 Univ Paris-Sud, UMR-S 776, Villejuif, F-94800, France. 6 DHU Hepatinov, Villejuif, F-94800, France
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21
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Khanna A, Gish R, Winter SC, Nyhan WL, Barshop BA. Successful Domino Liver Transplantation from a Patient with Methylmalonic Acidemia. JIMD Rep 2015. [PMID: 26219882 DOI: 10.1007/8904_2015_480] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
UNLABELLED Liver transplantation has been reported in patients with methylmalonic acidemia (MMA), but long-term outcome is controversial. Many patients with other approved indications for liver transplantation die before donor grafts are available. A 28-year-old man with MMA underwent cadaveric liver transplantation. His liver was used as a domino graft for a 61-year-old man with primary sclerosing cholangitis, who had low priority on the transplant waiting list. Surgical outcome was successful, and after transplantation both patients have excellent graft function. The patient with MMA showed substantial decrease in methylmalonate in urine (from 5,277 ± 1,968 preoperatively to 1,068 ± 384 mmol/mol creatinine) and plasma (from 445.9 ± 257.0 to 333.3 ± 117.7 μmol/l) over >1-year follow-up, while dietary protein intake increased from 0.6 to 1.36 ± 0.33 g/kg/day. The domino recipient maintained near-normal levels of plasma amino acids but did develop elevated methylmalonate in blood and urine while receiving an unrestricted diet (peak plasma methylmalonate 119 μmol/l and urine methylmalonate 84-209 mmol/mol creatinine, with 1.0-1.9 g/kg/day protein). Neither patient demonstrated any apparent symptoms of MMA or metabolic decompensation during the postoperative period or following discharge. CONCLUSION Liver transplantation substantially corrects methylmalonate metabolism in MMA and greatly attenuates the disease. In this single patient experience, a liver from a patient with MMA functioned well as domino graft although it did result in subclinical methylmalonic acidemia and aciduria in the recipient. Patients with MMA can be considered as domino liver donors for patients who might otherwise spend long times waiting for liver transplantation.
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Affiliation(s)
- A Khanna
- Department of Surgery and Center for Gut Rehabilitation and Transplantation, Transplant Center, Cleveland Clinic, Cleveland, OH, 44195, USA
| | - R Gish
- Department of Gastroenterology, Stanford University, Palo Alto, CA, 94305, USA
| | - S C Winter
- Department of Genetics, Children's Hospital of Central California, Madera, CA, 93636, USA
| | - W L Nyhan
- Department of Pediatrics, University of California San Diego and Rady Children's Hospital, San Diego, CA, 92093-0830, USA
| | - B A Barshop
- Department of Pediatrics, University of California San Diego and Rady Children's Hospital, San Diego, CA, 92093-0830, USA.
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22
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da Costa G, Ribeiro-Silva C, Ribeiro R, Gilberto S, Gomes RA, Ferreira A, Mateus É, Barroso E, Coelho AV, Freire AP, Cordeiro C. Transthyretin Amyloidosis: Chaperone Concentration Changes and Increased Proteolysis in the Pathway to Disease. PLoS One 2015; 10:e0125392. [PMID: 26147092 PMCID: PMC4492746 DOI: 10.1371/journal.pone.0125392] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Accepted: 03/24/2015] [Indexed: 11/18/2022] Open
Abstract
Transthyretin amyloidosis is a conformational pathology characterized by the extracellular formation of amyloid deposits and the progressive impairment of the peripheral nervous system. Point mutations in this tetrameric plasma protein decrease its stability and are linked to disease onset and progression. Since non-mutated transthyretin also forms amyloid in systemic senile amyloidosis and some mutation bearers are asymptomatic throughout their lives, non-genetic factors must also be involved in transthyretin amyloidosis. We discovered, using a differential proteomics approach, that extracellular chaperones such as fibrinogen, clusterin, haptoglobin, alpha-1-anti-trypsin and 2-macroglobulin are overrepresented in transthyretin amyloidosis. Our data shows that a complex network of extracellular chaperones are over represented in human plasma and we speculate that they act synergistically to cope with amyloid prone proteins. Proteostasis may thus be as important as point mutations in transthyretin amyloidosis.
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Affiliation(s)
- Gonçalo da Costa
- Centro de Química e Bioquímica, FCUL, Campo Grande, Lisboa, Portugal
| | | | - Raquel Ribeiro
- Centro de Química e Bioquímica, FCUL, Campo Grande, Lisboa, Portugal
| | - Samuel Gilberto
- Centro de Química e Bioquímica, FCUL, Campo Grande, Lisboa, Portugal
| | - Ricardo A Gomes
- Instituto de Tecnologia Química e Biológica, Av. da República Estação Agronómica Nacional, Oeiras, Portugal
| | - António Ferreira
- Centro de Química e Bioquímica, FCUL, Campo Grande, Lisboa, Portugal
| | - Élia Mateus
- Unidade de Transplantação, Hospital Curry Cabral, Lisboa, Portugal
| | - Eduardo Barroso
- Unidade de Transplantação, Hospital Curry Cabral, Lisboa, Portugal
| | - Ana V Coelho
- Instituto de Tecnologia Química e Biológica, Av. da República Estação Agronómica Nacional, Oeiras, Portugal
| | - Ana Ponces Freire
- Centro de Química e Bioquímica, FCUL, Campo Grande, Lisboa, Portugal
| | - Carlos Cordeiro
- Centro de Química e Bioquímica, FCUL, Campo Grande, Lisboa, Portugal
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23
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Adams D, Cauquil C, Theaudin M, Rousseau A, Algalarrondo V, Slama MS. Current and future treatment of amyloid neuropathies. Expert Rev Neurother 2014; 14:1437-51. [DOI: 10.1586/14737175.2014.983905] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Hori T, Egawa H, Kaido T, Ogawa K, Uemoto S. Liver transplantation for primary hyperoxaluria type 1: a single-center experience during two decades in Japan. World J Surg 2013; 37:688-693. [PMID: 23188539 DOI: 10.1007/s00268-012-1867-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Primary hyperoxaluria type-1 (PH1) is an autosomal recessive disorder caused by impaired activity of hepatic peroxisomal alanine-glyoxylate aminotransferase that leads to end-stage renal disease (ESRD). A definitive diagnosis is often delayed until ESRD appears. Based on the etiology, liver transplantation (LT) seems to be the definitive treatment. PATIENTS AND METHODS Three PH1 patients underwent LT at our institution during two decades. RESULTS Two of the patients had family histories of cryptogenic ESRD. All three showed disease onset in childhood, but the definitive diagnosis was delayed in two cases (17 and 37 years of age). These delayed cases resulted in ESRD, and hemodialysis (HD) had been introduced before LT. One patient received domino LT, and the other two underwent living-donor LT (LDLT). One patient finally died of sepsis, and was unable to receive a kidney transplantation (KT) after the domino LT. One patient did not show ESRD, and did not have to undergo KT after LDLT, although extracorporeal shock wave lithotripsy was required for residual ureterolithiasis (8 years after LDLT). The third patient had an uneventful course after LDLT and received living-donor KT from the same donor 8 months after LDLT. Subsequently, HD was successfully withdrawn. CONCLUSIONS Establishment of a definitive diagnosis of PH1 is essential. If a methodology for early diagnosis and an intensive care strategy for neonates and infants during the waiting time become well-established, a timely and preemptive LT alone can provide a good chance of cure for PH1 patients.
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Affiliation(s)
- Tomohide Hori
- Divisions of Hepato-Pancreato-Biliary, Transplant and Pediatric Surgery, Department of Surgery, Kyoto University, 54 Shogoinkawara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
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25
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Levesque E, Duclos J, Ciacio O, Adam R, Castaing D, Vibert E. Influence of larger graft weight to recipient weight on the post-liver transplantation course. Clin Transplant 2013; 27:239-47. [PMID: 23293941 DOI: 10.1111/ctr.12059] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/24/2012] [Indexed: 12/26/2022]
Abstract
Size matching between recipient and donor livers is an important factor in organ allocation in the context of liver transplantation (LT). The aim of this study was to determine whether a large graft for recipient size influenced the post-transplant course. One hundred and sixty-two successive LT recipients were included and retrospectively divided into two groups: 25 (15%) had a graft-to-recipient weight ratio (GWRW) ≥ 2.5% and 137 (85%) had a GWRW <2.5%. Postoperative complications and outcomes were recorded. In the GWRW >2.5% group, more end-to-end caval replacement (72% vs. 38%, p = 0.003) and veno-venous bypass (48% vs. 23%, p = 0.01) were used. Peak AST/ALT values were higher in the GWRW >2.5% group (AST: 596 [70-5876] vs. 453 [29-5132] IU/l, p = 0.03; ALT: 773 [101-5025] vs. 383 [36-4921] IU/l, p = 0.02). Among postoperative complications, the rate of respiratory failure was higher in the GWRW >2.5% group (32% vs. 14%, p = 0.04). The rates of other complications did not differ between the two groups. Both groups had similar graft and patient survival rates at one yr. Using large grafts for recipient size did not impair liver function and did not modify graft and patient outcomes at one yr. However, a GWRW >2.5% appeared to be a determining factor for respiratory morbidity following LT.
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Affiliation(s)
- Eric Levesque
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France.
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26
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Dai WC, Chan SC, Chok KSH, Cheung TT, Sharr WW, Chan ACY, Fung JYY, Tsang SHY, Fan ST, Lo CM. Single-centre experience of liver transplantation for familial amyloidotic polyneuropathy of non-Val30Met variants in Chinese patients. Amyloid 2012; 19:33-36. [PMID: 22320251 DOI: 10.3109/13506129.2012.655867] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
OBJECTIVE To review our experience of liver transplantation (LT) for patients with non-Val30Met familial amyloidotic polyneuropathy (FAP) and patients receiving FAP livers. METHOD Data of six FAP patients and five FAP liver recipients, all Chinese, were reviewed. RESULTS Among the six FAP patients, five patients were of the V30A variant and one patient was of the G67E variant. One patient had malnutrition. Three patients had peripheral neuropathy. Four patients had orthostatic hypotension. Five patients had cardiac involvement. Two patients underwent living-donor LT and four patients underwent deceased-donor LT. One patient had progressive cardiac and neurological involvement after transplantation. Three patients showed either improvement or a static condition. All five FAP liver recipients had hepatitis-B-related hepatocellular carcinoma before transplantation. With a median follow-up period of 49 months, all of them survived without tumour recurrence. The first recipient developed systemic transthyretin amyloidosis six years after transplantation. Upper endoscopy confirmed the presence of gastric amyloidosis, and nerve conduction test showed evidence of axonal sensorimotor polyneuropathy. CONCLUSIONS Most of the FAP patients and FAP liver recipients displayed satisfactory outcomes after transplantation. LT halted disease progression in the FAP patients who had early presentation of the disease.
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27
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Tran NQ, Malcontenti-Wilson C, Hammoud S, Millar I, Christophi C, Muralidharan V. Hyperbaric oxygen therapy reduces the severity of ischaemia, preservation and reperfusion injury in a rat model of liver transplantation. HPB (Oxford) 2012; 14:103-14. [PMID: 22221571 PMCID: PMC3277052 DOI: 10.1111/j.1477-2574.2011.00410.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Approaches to increase organ availability for orthotopic liver transplantation (OLT) often result in the procurement of marginal livers that are more susceptible to ischaemia, preservation and reperfusion injury (IPRI). METHODS The effects of post-OLT hyperbaric oxygen (HBO) therapy on IPRI in a syngeneic rat OLT model were examined at various time-points. The effects of IPRI and HBO on hepatocyte necrosis, apoptosis, proliferation, and sinusoidal morphology and ultrastructure were assessed. RESULTS Post-OLT HBO therapy significantly reduced the severity of IPRI; both apoptosis [at 12 h: 6.4 ± 0.4% in controls vs. 1.6 ± 0.7% in the HBO treatment group (p < 0.001); at 48 h: 2.4 ± 0.2% in controls vs. 0.4 ± 0.1% in the HBO treatment group (p < 0.001)] and necrosis [at 12 h: 18.7 ± 1.8% in controls vs. 2.4 ± 0.4% in the HBO treatment group (p < 0.001); at 48 h: 8.5 ± 1.3% in controls vs. 3.4 ± 0.9% in the HBO treatment group (P= 0.019)] were decreased. Serum alanine transaminase was reduced [at 12 h: 1068 ± 920 IU/l in controls vs. 370 ± 63 IU/l in the HBO treatment group (P= 0.030); at 48 h: 573 ± 261 IU/l in controls vs. 160 ± 10 IU/l in the HBO treatment group (P= 0.029)]. Treatment with HBO also promoted liver regeneration [proliferation at 12 h: 4.5 ± 0.1% in controls vs. 1.0 ± 0.3% in the HBO treatment group (p < 0.001); at 48 h: 8.6 ± 0.7% in controls vs. 2.9 ± 0.2% in the HBO treatment group (p < 0.01)] and improved sinusoidal diameter and microvascular density index. CONCLUSIONS Hyperbaric oxygen therapy has persistent positive effects post-OLT that may potentially transfer into clinical practice.
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Affiliation(s)
- Nhut Quang Tran
- Department of Surgery, The University of Melbourne, Austin HealthHeidelberg, Vic, Australia
| | | | - Soukena Hammoud
- Department of Surgery, The University of Melbourne, Austin HealthHeidelberg, Vic, Australia
| | - Ian Millar
- Hyperbaric Unit, Alfred HospitalPrahran, Vic, Australia
| | - Chris Christophi
- Department of Surgery, The University of Melbourne, Austin HealthHeidelberg, Vic, Australia
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28
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Abstract
Domino liver transplantation (DLT) has emerged as a strategy for increasing the number of liver grafts available: morphologically normal livers from donors with metabolic diseases can be used for select recipients with hepatocellular carcinoma (usually outside the Milan criteria). Familial amyloidotic polyneuropathy (FAP) is the most common indication for DLT. When FAP patients are involved in DLT, the indications and outcomes are clear and good, although de novo FAP development within various periods of time has been described in DLT recipients of FAP livers. With the increasing need for organs, livers explanted from patients with rare metabolic diseases, such as primary hyperoxaluria (PH), acute intermittent porphyria (AIP), maple syrup urine disease (MSUD), and homozygous familial hypercholesterolemia (HFHC), are being used for DLT. However, insufficient data about the use of livers from patients with these rare metabolic diseases are available. In this review, we focus on the latter disorders. PH is not a good indication for DLT because recipients of PH livers develop hyperoxaluria and early acute renal failure. AIP also seems to be a debatable indication for DLT because of the rapid development of neurotoxicity in AIP liver recipients. However, the outcomes of DLT with HFHC and MSUD liver grafts (which include the risk of the de novo development of these genetic diseases) are promising. For rare metabolic liver diseases to be established as indications for DLT, more reports and studies are needed.
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Affiliation(s)
- Irinel Popescu
- Center of Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania.
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29
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Beyond genetic factors in familial amyloidotic polyneuropathy: protein glycation and the loss of fibrinogen's chaperone activity. PLoS One 2011; 6:e24850. [PMID: 22053176 PMCID: PMC3203866 DOI: 10.1371/journal.pone.0024850] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2011] [Accepted: 08/19/2011] [Indexed: 02/06/2023] Open
Abstract
Familial amyloidotic polyneuropathy (FAP) is a systemic conformational disease characterized by extracellular amyloid fibril formation from plasma transthyretin (TTR). This is a crippling, fatal disease for which liver transplantation is the only effective therapy. More than 80 TTR point mutations are associated with amyloidotic diseases and the most widely accepted disease model relates TTR tetramer instability with TTR point mutations. However, this model fails to explain two observations. First, native TTR also forms amyloid in systemic senile amyloidosis, a geriatric disease. Second, age at disease onset varies by decades for patients bearing the same mutation and some mutation carrier individuals are asymptomatic throughout their lives. Hence, mutations only accelerate the process and non-genetic factors must play a key role in the molecular mechanisms of disease. One of these factors is protein glycation, previously associated with conformational diseases like Alzheimer's and Parkinson's. The glycation hypothesis in FAP is supported by our previous discovery of methylglyoxal-derived glycation of amyloid fibrils in FAP patients. Here we show that plasma proteins are differentially glycated by methylglyoxal in FAP patients and that fibrinogen is the main glycation target. Moreover, we also found that fibrinogen interacts with TTR in plasma. Fibrinogen has chaperone activity which is compromised upon glycation by methylglyoxal. Hence, we propose that methylglyoxal glycation hampers the chaperone activity of fibrinogen, rendering TTR more prone to aggregation, amyloid formation and ultimately, disease.
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30
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Kitchens WH. Domino liver transplantation: indications, techniques, and outcomes. Transplant Rev (Orlando) 2011; 25:167-77. [PMID: 21803558 DOI: 10.1016/j.trre.2011.04.002] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2011] [Accepted: 04/26/2011] [Indexed: 02/07/2023]
Abstract
The long-term shortage of livers available for transplantation has spurred the development of many strategies to bolster the donor organ supply. One particularly innovative strategy is domino liver transplantation in which a select group of liver transplant recipients can donate their explanted native livers for use as liver grafts in other patients. Several hereditary metabolic diseases (such as familial amyloid polyneuropathy, maple syrup urine disease, and familial hypercholesterolemia) are caused by aberrant or deficient protein production in the liver, and these conditions can be cured with an orthotopic liver transplant. Although their native livers eventually caused severe systemic disease in these patients, these livers are otherwise structurally and functionally normal, and they have been used successfully in domino liver transplants for the past 15 years. This article will review the indications for donating or receiving a domino liver transplant, the surgical techniques necessary to perform these transplants, as well as the recently revealed long-term outcomes and risks of domino transplantation.
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31
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Corruble E, Barry C, Varescon I, Falissard B, Castaing D, Samuel D. Depressive symptoms predict long-term mortality after liver transplantation. J Psychosom Res 2011; 71:32-7. [PMID: 21665010 DOI: 10.1016/j.jpsychores.2010.12.008] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2010] [Revised: 11/29/2010] [Accepted: 12/14/2010] [Indexed: 01/27/2023]
Abstract
OBJECTIVE Depressive symptoms are common after liver transplantation (LT). We studied whether depressive symptoms affect long-term survival after LT. METHODS In a prospective cohort study, 134 liver transplant patients were assessed for depressive symptoms using the Beck Depression Inventory-short form (BDI), focusing on the 3 months post-LT score and on the score change from the waiting list period. They were followed up for long-term survival. The median duration of the follow-up period was 43 months post-LT. None of the 134 patients was lost to follow-up for survival. RESULTS A total of 33.6% of the LT patients had mild to moderate depressive symptoms 3 months post-LT. Eighteen (13.4%) patients died during the follow-up. Using Cox proportional hazards analysis, depressive symptoms were significantly associated with mortality (hazard ratio [HR] 1.22, 95% confidence interval (CI) 1.07-1.40, P<.003), one more point in the BDI score being associated with a 17% increase in mortality risk. Other predictive factors of mortality were older age and hepatitis C virus with recurrence 3 months post-LT. Similarly, an increase in depressive symptoms between the waiting list and 3 months post-LT periods predicted mortality (HR 1.18, 95% CI 1.01-1.38, P=.03), especially for patients without depressive symptoms on waiting list (HR 1.56, 95% CI 1.16-2.12, P=.004). CONCLUSION Depressive symptoms after LT and an increase in depressive symptoms between the waiting list and post-LT are associated with an increased risk of long-term mortality. Interventions that could reduce depressive symptoms could potentially decrease long-term mortality after LT.
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Affiliation(s)
- Emmanuelle Corruble
- INSERM U 669, Paris XI University, Psychiatry Department, Bicêtre University Hospital, Assistance Publique—Hopitaux de Paris, Paris, France.
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32
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Adams D, Lacroix C, Antonini T, Lozeron P, Denier C, Kreib AM, Epelbaum S, Blandin F, Karam V, Azoulay D, Adam R, Castaing D, Samuel D. Symptomatic and proven de novo amyloid polyneuropathy in familial amyloid polyneuropathy domino liver recipients. Amyloid 2011; 18 Suppl 1:174-7. [PMID: 21838477 DOI: 10.3109/13506129.2011.574354065] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- D Adams
- French Reference Center for FAP, Université Paris Sud, Paris, France.
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Cania A, Bergesio F, Curciarello G, Perfetto F, Ciciani AM, Nigrelli S, Minuti B, Caldini AL, Di Lollo S, Nozzoli C, Salvadori M. The Florence Register of amyloidosis: 20 years' experience in the diagnosis and treatment of the disease in the Florence district area. Amyloid 2011; 18 Suppl 1:86-88. [PMID: 21838443 DOI: 10.3109/13506129.2011.574354] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
- A Cania
- Florence Center for the study and treatment of Amyloidosis, Florence, Italy
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34
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Tincani G, Hoti E, Andreani P, Ricca L, Pittau G, Vitale V, Blandin F, Adam R, Castaing D, Azoulay D. Operative risks of domino liver transplantation for the familial amyloid polyneuropathy liver donor and recipient: a double analysis. Am J Transplant 2011; 11:759-66. [PMID: 21446978 DOI: 10.1111/j.1600-6143.2011.03477.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Although domino liver transplantation (LT) is an established procedure, data about the operative risks are limited. This study aimed at evaluating the operative risks of domino LT. Two retrospective analyses were conducted (comparison of familial amyloid polyneuropathy [FAP] liver donors [61 patients] vs. FAP nondonors [39 patients] and FAP liver recipients [61 patients] vs. deceased donor liver recipients [61 patients]). First analysis showed a 60-day mortality of 6.6% for FAP donors and 7.7% for FAP nondonors (p = 1.0). No patient developed primary graft nonfunction. Acute rejection was higher in FAP nondonors compared to FAP donors (38.5% vs. 13.1%). Both groups had similar vascular and biliary complication rates. ICU stay was similar, whereas total hospitalization was longer for FAP nondonors. Both groups had similar 1- and 5-year patient and graft survival rates (83.4% vs. 87.2%, and 79.8% vs. 71.8%, p = 0.7) and (83.3% vs. 87.2%, and 79.1% vs.71.8%, p = 0.7). The second analysis showed a 1.6% mortality for FAP liver recipients vs. 3.2% of the control group (p = 1). Both groups had similar morbidity and technical complication rates (18.0% vs. 13.1%, p = 0.45) and (0.18 vs. 0.15, p = 0.65). The domino procedure does not add any risk to FAP donor or recipient. It increases the organ pool allowing transplantation of marginal recipients who otherwise are denied deceased donor liver transplantation.
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Affiliation(s)
- G Tincani
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France
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35
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Abstract
This mini-review on European experiences with tackling the problem of organ shortage for transplantation was based on a literature review of predominantly European publications dealing with the issue of organ donation from deceased donors. The authors tried to identify the most significant factors that have demonstrated to impact on donation rates from deceased donors and subsequent transplant successes. These factors include legislative measures (national laws and European Directives), optimization of the donation process, use of expanded criteria donors, innovative preservation and surgical techniques, organizational efforts, and improved allocation algorithms.
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Affiliation(s)
- Leo Roels
- Donor Action Foundation, Linden, Belgium
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Abstract
This paper describes the rapid evolution of modern liver surgery, starting in the middle of the twentieth century. Claude Couinaud studied and described the segmental anatomy of the liver, Thomas Starzl performed the first liver transplantations, and Henri Bismuth introduced the concept of anatomical resections. Hepatic surgery has developed significantly since those early days. To date, innovative techniques are applied, using cutting-edge technologies: Intraoperative ultrasound, techniques of vascular exclusion of the liver, new devices for performing homeostasis and dissection, laparoscopy for resections, and new drugs that allow the resection of previously unresectable tumors. The next stage in liver surgery will probably be the implementation of a multidisciplinary holistic approach to the liver-diseased patient that will ensure the best and most efficient treatments in the future.
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Affiliation(s)
- Henri Bismuth
- Hepatobiliary Institute, Paul Brousse Hospital, Paris, France, and
- To whom correspondence should be addressed. E-mail:
| | - Rony Eshkenazy
- Hepato-Biliary Surgery Service, Department of General Surgery, Rambam Health Care Campus, Haifa, Israel
| | - Arie Arish
- Hepato-Biliary Surgery Service, Department of General Surgery, Rambam Health Care Campus, Haifa, Israel
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Lladó L, Baliellas C, Casasnovas C, Ferrer I, Fabregat J, Ramos E, Castellote J, Torras J, Xiol X, Rafecas A. Risk of transmission of systemic transthyretin amyloidosis after domino liver transplantation. Liver Transpl 2010; 16:1386-92. [PMID: 21117248 DOI: 10.1002/lt.22174] [Citation(s) in RCA: 75] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Recent reports of the transmission of systemic transthyretin (TTR) amyloidosis after domino liver transplantation (DLT) using grafts from patients with familial amyloid polyneuropathy (FAP) have raised concerns about the procedure. The aim of this study was to evaluate the transmission incidence of systemic TTR amyloidosis after DLT with a complete clinical, neurological, and pathological assessment. At our institution, DLT has been performed 31 times with livers from patients with FAP. Seventeen of the 19 patients still alive in 2008 agreed to enter the study. This cross-sectional study of this cohort of patients included clinical assessments, rectal biopsy, and electroneuromyography (as well as sural nerve biopsy when it was indicated). The mean follow-up at the time of the study was 62.6 ± 2.9 months. Clinically, 3 patients complained of weak dysesthesia. When a focused study was performed, 8 patients reported some kind of neurological and/or gastrointestinal disturbance. Six of the rectal biopsy samples showed amyloid deposits (TTR-positive). Electromyography (EMG) showed signs of mild sensorimotor neuropathy in 3 cases and moderate to severe sensorimotor neuropathy in 1 case. Only 2 of the 4 patients with EMG signs of polyneuropathy showed amyloid deposits in their rectal biopsy samples. Sural nerve biopsy revealed amyloid deposits (TTR-positive) in all 4 patients with EMG signs of polyneuropathy. Two patients with normal EMG findings had TTR-positive amyloid deposits in their sural nerve biopsy samples. In conclusion, de novo systemic amyloidosis after DLT may be more frequent and appear earlier than was initially thought. In our opinion, however, the graft shortage still justifies DLT in selected patients, despite the risk of de novo systemic amyloidosis. Sural nerve biopsy with EMG and clinical correlation is mandatory for confirming the disease. Indeed, other causes of neuropathy should be excluded.
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Affiliation(s)
- Laura Lladó
- Departments of Surgery, Liver Transplant Unit, Hospital Universitari de Bellvitge, IDIBELL, Barcelona, Spain.
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Early Renal Failure After Domino Liver Transplantation Using Organs From Donors With Primary Hyperoxaluria Type 1. Transplantation 2010; 90:782-5. [DOI: 10.1097/tp.0b013e3181eefe1f] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Bhoori S, Sposito C, Germini A, Coppa J, Mazzaferro V. The challenges of liver transplantation for hepatocellular carcinoma on cirrhosis. Transpl Int 2010; 23:712-22. [PMID: 20492616 DOI: 10.1111/j.1432-2277.2010.01111.x] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide and liver transplantation (LT) has potentials to improve survival for patients with HCC. However, expansion of indications beyond Milan Criteria (MC) and use of bridging/downstaging procedures to convert intermediate-advanced stages of HCC within MC limits are counterbalanced by graft shortage and increasing use of marginal donors, partially limited by the use of donor-division protocols applied to the cadaveric and living-donor settings. Several challenges in technique, indications, pre-LT treatments and prioritization policies of patients on the waiting list have to be precised through prospective investigations that have to include individualization of prognosis, biological variables and pathology surrogates as stratification criteria. Also, liver resection has to be rejuvenated in the general algorithm of HCC treatment in the light of salvage transplantation strategies, while benefit of LT for HCC should be determined through newly designed composite scores that are able to capture both efficiency and equity endpoints. Innovative treatments such as radioembolization for HCC associated with portal vein thrombosis and molecular targeted compounds are likely to influence future strategies. Accepting this challenge has been part of the history of LT and will endure so also for the future.
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Affiliation(s)
- Sherrie Bhoori
- Liver Unit and Hepato-Oncology Group, National Cancer Institute, Fondazione Istituto Nazionale Tumori, Milan, Italy
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Vibert E, Azoulay D, Hoti E, Iacopinelli S, Samuel D, Salloum C, Lemoine A, Bismuth H, Castaing D, Adam R. Progression of alphafetoprotein before liver transplantation for hepatocellular carcinoma in cirrhotic patients: a critical factor. Am J Transplant 2010; 10:129-37. [PMID: 20070666 DOI: 10.1111/j.1600-6143.2009.02750.x] [Citation(s) in RCA: 199] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liver transplantation (LT) for cirrhotic/Hepatocellular carcinoma (HCC) is associated with reduced survival in patients with poor histological features. Preoperative levels of alphafetoprotein (AFP) could predict negative biological features. AFP progression could be more relevant than static AFP levels in predicting LT outcomes. A total of 252 cirrhotic/HCC patients transplanted between 1985 and 2005 were reviewed. One hundred fifty-three patients were analyzed, 99 excluded (for nonsecreting tumors and/or salvage transplantation). Using receiver operating characteristics analysis for recurrence after LT, 'progression' of AFP was defined by >15 microg/L per month before LT. A total of 127 (83%) were transplanted under and 26 (16%) over this threshold. After 45 months of follow-up (median), 5-year overall survival (OS) and recurrence free-survival (RFS) were 72% and 69%, respectively. Five-year survival in the progression group was lower than the nonprogression group (OS 54% vs. 77%; RFS 47% vs. 74%). Multivariate analysis showed progression of AFP>15 microg/L per month and preoperative nodules>3 were associated with decreased OS. Progression group and age>60 years were associated with decreased RFS. Male gender, progression of AFP and size of tumor>30 mm were associated with satellite nodules and/or vascular invasion. In conclusion, increasing AFP>15 microg/L/month while waiting for LT is the most relevant preoperative prognostic factor for low OS/DFS. AFP progression could be a pathological preoperative marker of tumor aggressiveness.
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Affiliation(s)
- E Vibert
- AP-HP, Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm, Unite 785, Université Paris-Sud, Villejuif, France
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41
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Abstract
BACKGROUND Simultaneous combined orthotopic heart and liver transplantation (CHLTx) remains a lifesaving procedure for the patients suffering from coincident end-stage heart and liver disease and several metabolic disorders. We analyze the long-term outcome of the patients undergoing CHLTx. METHODS Between January 1992 and May 2007, 15 CHLTx were attempted at the Mayo Clinic including two combined heart, liver, and kidney transplantations and one combined heart, lung, and liver transplantations. Pretransplant cardiac diagnoses were familial amyloidosis (11), hemochromatosis (1), restrictive cardiomyopathy and cardiac cirrhosis (1), previously operated congenital heart disease and cardiac cirrhosis (1), and primary pulmonary hypertension with primary biliary cirrhosis (1). RESULTS Heart and liver transplantation were performed as a single combined procedure in 13 (93%) hemodynamically stable patients, and there was no perioperative mortality. Survival rates for the CHLTx recipients at 1 year, 5 years, and 10 years were 100%, 75%, and 60%, respectively, and did not differ from survival after isolated heart transplantation (93%, 83%, and 65%, respectively, P=0.39). Freedom from cardiac allograft rejection (ISHLT > or =grade 2) for CHLTx was 83% at 1 month, did not change with time, and was lower than after isolated heart transplantation (P=0.02). At the mean follow-up of 61.6+/-53.6 months, normal left ventricular ejection fraction and good liver allograft function were demonstrated. Three patients developed end-stage renal failure secondary to calcineurin nephrotoxicity. CONCLUSION Simultaneous heart and liver transplantation is feasible and achieved excellent results for selected patients.
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Polak WG, Peeters PM, Slooff MJ. The evolution of surgical techniques in clinical liver transplantation. A review. Clin Transplant 2009; 23:546-64. [DOI: 10.1111/j.1399-0012.2009.00994.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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43
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Muscari F, Guinard JP, Foppa B, Trocard P, Danjoux M, Kamel MS, Duffas JP, Rostaing L, Fourtanier G, Suc B. Biological changes after liver transplantation according to the presence or not of graft steatosis. Transplant Proc 2009; 40:3562-5. [PMID: 19100438 DOI: 10.1016/j.transproceed.2008.06.087] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2007] [Revised: 05/13/2008] [Accepted: 06/18/2008] [Indexed: 01/22/2023]
Abstract
AIM To assess the consequences of graft steatosis on postoperative liver function as compared with normal liver grafts. PATIENTS AND METHODS From January 2005 to December 2007, liver transplant patients were prospectively included, excluding those who experienced arterial or biliary complications or presented acute rejection. All patients had a surgical biopsy after reperfusion. Patients were compared according to the rate of macrovacuolar steatosis: namely above or below 20%. RESULTS Fifty-three patients were included: 10 in the steatosis group and 43 in the control group. No significant difference was observed in terms of morbidity, mortality, and primary non- or poor function. Nevertheless, biological changes after the procedure were significantly different during the first postoperative week. Prothrombin time, serum bilirubin, and transaminases were significantly increased among the steatosis group compared with the control group (P < .05). CONCLUSION This case-controlled study including a small number of patients, described postoperative biological changes among liver transplantations with steatosis in the graft.
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Affiliation(s)
- F Muscari
- Digestive and Liver Transplantation Department, CHU Rangueil, Toulouse, France.
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44
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Adams D, Lacroix C, Antonini T, Lozeron P, Denier C, Epelbaum S, Karam V, Blandin F, Azulay D, Adam R, Castaing D, Samuel D. Risque de neuropathie amyloïde à transthyrétine de novo après transplantation hépatique Domino de neuropathie amyloïde familiale (NAF). Rev Neurol (Paris) 2009. [DOI: 10.1016/s0035-3787(09)70019-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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45
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Popescu I, Habib N, Dima S, Hancu N, Gheorghe L, Iacob S, Mihaila M, Dorobantu B, Matei E, Botea F. Domino liver transplantation using a graft from a donor with familial hypercholesterolemia: seven-yr follow-up. Clin Transplant 2008; 23:565-70. [PMID: 19191809 DOI: 10.1111/j.1399-0012.2008.00935.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
A 46-yr-old female with hepatocellular carcinoma and severe hepatitis B-related liver cirrhosis received a domino liver graft from a 25-yr-old female with homozygous familial hypercholesterolemia (HFHC) in September 2001. Hypercholesterolemia occurred in the graft recipient within one yr after transplantation and was partially controlled by atorvastatin. Three yr after transplantation, an autologous CD34(+) cell transplantation was performed in order to better control the hypercholesterolemia. Only preliminary results of this domino liver transplantation (DLT) were published in 2003, without a long-term analysis of the hypercholesterolemic effects in recipient. Subsequent to DLT, the average plasma cholesterol level in the domino donor rapidly normalized and seven yr after had a value of 182 mg/dL. After seven-yr follow-up, the domino recipient has no hepatocarcinoma recurrence. Moreover, no signs of cardiovascular or atherosclerotic lesions were noted despite an elevated plasma cholesterol level (339 mg/dL after seven yr of follow-up) resistant to drug therapy and stem cell autotransplantation. In conclusion, DLT using a liver graft from a patient with HFHC provides a viable option for marginal recipients.
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Affiliation(s)
- Irinel Popescu
- Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania.
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Duclos-Vallée JC, Féray C, Sebagh M, Teicher E, Roque-Afonso AM, Roche B, Azoulay D, Adam R, Bismuth H, Castaing D, Vittecoq D, Samuel D. Survival and recurrence of hepatitis C after liver transplantation in patients coinfected with human immunodeficiency virus and hepatitis C virus. Hepatology 2008; 47:407-17. [PMID: 18098295 DOI: 10.1002/hep.21990] [Citation(s) in RCA: 148] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
UNLABELLED Liver transplantation in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is a recent indication. In a single center, we have compared the survival and severity of recurrent HCV infection after liver transplantation in HIV-HCV-coinfected and HCV-monoinfected patients. Seventy-nine patients receiving a first liver graft for HCV-related liver disease between 1999 and 2005 were included. Among them, 35 had highly active antiretroviral therapy-controlled HIV infection. All patients were monitored for HCV viral load and liver histology during the posttransplantation course. Coinfected patients were younger (43 +/- 6 versus 55 +/- 8 years, P < 0.0001) and had a higher Model for End-Stage Liver Disease (MELD) score (18.8 +/- 7.4 versus 14.8 +/- 4.7; P = 0.008). The 2-year and 5-year survival rates were 73% and 51% and 91% and 81% in coinfected patients and monoinfected patients, respectively (log-rank P = 0.004). Under multivariate Cox analysis, survival was related only to the MELD score (P = 0.03; risk ratio, 1.08; 95% confidence interval, 1.01, 1.15). Using the Kaplan-Meier method, the progression to fibrosis >or= F2 was significantly higher in the coinfected group (P < 0.0001). CONCLUSION The results of liver transplantation in HIV-HCV-coinfected patients were satisfactory in terms of survival benefit. Earlier referral of these patients to a liver transplant unit, the use of new drugs effective against HCV, and an avoidance of drug toxicity are mandatory if we are to improve the results of this challenging indication for liver transplantation.
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47
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Samuel D, Adams D. Domino liver transplantation from familial amyloidotic polyneuropathy donors: how close is the damocles sword to the recipient? Transpl Int 2007; 20:921-3. [DOI: 10.1111/j.1432-2277.2007.00534.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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di Francesco F, Cautero N, De Luca S, Vecchi A, Garelli P, Doria C, Marino IR, Risaliti A. Reconstruction of the suprahepatic cuff injured during multiorgan procurement using the infrahepatic vena cava of the liver allograft. Liver Transpl 2007; 13:1468-9. [PMID: 17902134 DOI: 10.1002/lt.21195] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Fabrizio di Francesco
- Chirurgia Epatobiliopancreatica e dei Trapianti di Fegato, Rene e Pancreas, Azienda Ospedaliero-Universitaria Ospedali Riuniti Ancona, Ancona, Italy.
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Takei YI, Gono T, Yazaki M, Ikeda SI, Ikegami T, Hashikura Y, Miyagawa SI, Hoshii Y. Transthyretin-derived amyloid deposition on the gastric mucosa in domino recipients of familial amyloid polyneuropathy liver. Liver Transpl 2007; 13:215-8. [PMID: 17029284 DOI: 10.1002/lt.20954] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Familial amyloid polyneuropathy (FAP) is a form of hereditary generalized amyloidosis. Liver tissue explanted from FAP patients has normal structure and function, except for the production of amyloidogenic variant transthyretin (TTR), and domino liver transplantation (DLT) using grafts from FAP patients was first performed in 1995. FAP symptoms usually develop in genetically determined individuals after the age of 20, but it is difficult to estimate when FAP symptoms will appear in domino recipients. Concerning this problem, histological findings showing amyloid deposition have recently been obtained in a few domino recipients of FAP livers. This study investigated the presence of de novo amyloid deposition in the gastroduodenal mucosa of domino recipients transplanted at our institution. Biopsy of gastroduodenal mucosa was carried out in 5 recipients of FAP livers and TTR-derived amyloid deposits were detected in 2 patients, both of whom had undergone DLT 47 months previously. In FAP liver recipients, de novo systemic amyloid deposition may begin much sooner than previously supposed. Therefore, careful follow-up of domino recipients of FAP livers is required.
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Affiliation(s)
- Yo-ichi Takei
- Department of Internal Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan.
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Abstract
Liver transplantation is the treatment of choice for end stage liver disease and is often used for primary liver malignancies. The main limitation of its wider application is the availability of suitable donor organs. The use of marginal donor organs, split-liver transplantation and living-related liver transplantation techniques contribute to increase the donor pool. However, the use of these techniques is associated with a higher risk of post transplantation organ dysfunction, predominantly due to ischaemia, preservation and reperfusion injury (IPRI). A number of studies have demonstrated that hyperbaric oxygen (HBO) therapy influences IPRI and consequential acute cellular rejection. This article reviews the rationale of HBO therapy in the field of transplantation with particular emphasis on liver transplantation.
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