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Chopinet S, Lopez O, Brustlein S, Uzel A, Moyon A, Varlet I, Balasse L, Kober F, Bobot M, Bernard M, Haffner A, Sdika M, Montcel B, Guillet B, Vidal V, Grégoire E, Hardwigsen J, Brige P. Comparing Different Methods for the Diagnosis of Liver Steatosis: What Are the Best Diagnostic Tools? Diagnostics (Basel) 2024; 14:2292. [PMID: 39451615 PMCID: PMC11506074 DOI: 10.3390/diagnostics14202292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 10/07/2024] [Accepted: 10/09/2024] [Indexed: 10/26/2024] Open
Abstract
BACKGROUND Due to the ongoing organ shortage, marginal grafts with steatosis are more frequently used in liver transplantation, leading to higher occurrences of graft dysfunction. A histological analysis is the gold standard for the quantification of liver steatosis (LS), but has its drawbacks: it is an invasive method that varies from one pathologist to another and is not available in every hospital at the time of organ procurement. This study aimed to compare non-invasive diagnostic tools to a histological analysis for the quantification of liver steatosis. METHODS Male C57BL6J mice were fed with a methioninecholine-deficient (MCD) diet for 14 days or 28 days to induce LS, and were compared to a control group of animals fed with a normal diet. The following non-invasive techniques were performed and compared to the histological quantification of liver steatosis: magnetic resonance spectroscopy (MRS), CARS microscopy, 99mTc MIBI SPECT imaging, and a new near-infrared spectrometer (NIR-SG1). RESULTS After 28 days on the MCD diet, an evaluation of LS showed ≥30% macrovesicular steatosis. High correlations were found between the NIR-SG1 and the blinded pathologist analysis (R2 = 0.945) (p = 0.001), and between the CARS microscopy (R2 = 0.801 (p < 0.001); MRS, R2 = 0.898 (p < 0.001)) and the blinded pathologist analysis. The ROC curve analysis showed that the area under the curve (AUC) was 1 for both the NIR-SG1 and MRS (p = 0.021 and p < 0.001, respectively), while the AUC = 0.910 for the Oil Red O stain (p < 0.001) and the AUC = 0.865 for the CARS microscopy (p < 0.001). The AUC for the 99mTc MIBI SPECT was 0.640 (p = 0.013), and this was a less discriminating technique for LS quantification. CONCLUSIONS The best-performing non-invasive methods for LS quantification are MRS, CARS microscopy, and the NIR-SG1. The NIR-SG1 is particularly appropriate for clinical practice and needs to be validated by clinical studies on liver grafts.
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Affiliation(s)
- Sophie Chopinet
- Department of Digestive Surgery and Liver Transplantation, Hôpital la Timone, AP-HM, 13005 Marseille, France;
- Aix Marseille Université, LIIE, 13007 Marseille, France; (O.L.); (V.V.); (E.G.); (P.B.)
- Aix Marseille Université, CERIMED, 13007 Marseille, France; (S.B.); (L.B.); (M.B.); (B.G.)
| | - Olivier Lopez
- Aix Marseille Université, LIIE, 13007 Marseille, France; (O.L.); (V.V.); (E.G.); (P.B.)
- Aix Marseille Université, CERIMED, 13007 Marseille, France; (S.B.); (L.B.); (M.B.); (B.G.)
- Department of Digestive and Oncologic Radiology, Hôpital l’Archet 2, 06202 Nice, France
| | - Sophie Brustlein
- Aix Marseille Université, CERIMED, 13007 Marseille, France; (S.B.); (L.B.); (M.B.); (B.G.)
| | - Antoine Uzel
- INSA-Lyon, Université Lyon 1, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR5220, U1294, 69616 Lyon, France; (A.U.); (M.S.); (B.M.)
| | - Anais Moyon
- C2VN, INSERM 1263 INRAE 1260, Aix-Marseille Université, 13007 Marseille, France;
- Department of Radiopharmacy, Hôpital la Timone, AP-HM, 13007 Marseille, France
| | - Isabelle Varlet
- Aix-Marseille Université, CNRS, CRMBM, 13007 Marseille, France; (I.V.); (F.K.); (M.B.)
| | - Laure Balasse
- Aix Marseille Université, CERIMED, 13007 Marseille, France; (S.B.); (L.B.); (M.B.); (B.G.)
| | - Frank Kober
- Aix-Marseille Université, CNRS, CRMBM, 13007 Marseille, France; (I.V.); (F.K.); (M.B.)
| | - Mickaël Bobot
- Aix Marseille Université, CERIMED, 13007 Marseille, France; (S.B.); (L.B.); (M.B.); (B.G.)
- C2VN, INSERM 1263 INRAE 1260, Aix-Marseille Université, 13007 Marseille, France;
- Center of Nephrology and Kidney Transplantation, Hôpital de la Conception, AP-HM, 13005 Marseille, France
| | - Monique Bernard
- Aix-Marseille Université, CNRS, CRMBM, 13007 Marseille, France; (I.V.); (F.K.); (M.B.)
| | - Aurélie Haffner
- Department of Anatomopathology, Hôpital la Timone, AP-HM, 13007 Marseille, France;
| | - Michaël Sdika
- INSA-Lyon, Université Lyon 1, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR5220, U1294, 69616 Lyon, France; (A.U.); (M.S.); (B.M.)
| | - Bruno Montcel
- INSA-Lyon, Université Lyon 1, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR5220, U1294, 69616 Lyon, France; (A.U.); (M.S.); (B.M.)
| | - Benjamin Guillet
- Aix Marseille Université, CERIMED, 13007 Marseille, France; (S.B.); (L.B.); (M.B.); (B.G.)
- C2VN, INSERM 1263 INRAE 1260, Aix-Marseille Université, 13007 Marseille, France;
- Department of Radiopharmacy, Hôpital la Timone, AP-HM, 13007 Marseille, France
| | - Vincent Vidal
- Aix Marseille Université, LIIE, 13007 Marseille, France; (O.L.); (V.V.); (E.G.); (P.B.)
- Aix Marseille Université, CERIMED, 13007 Marseille, France; (S.B.); (L.B.); (M.B.); (B.G.)
- Aix-Marseille Université, 27 Boulevard Jean Moulin, 13385 Marseille, France
| | - Emilie Grégoire
- Aix Marseille Université, LIIE, 13007 Marseille, France; (O.L.); (V.V.); (E.G.); (P.B.)
- Aix Marseille Université, CERIMED, 13007 Marseille, France; (S.B.); (L.B.); (M.B.); (B.G.)
| | - Jean Hardwigsen
- Department of Digestive Surgery and Liver Transplantation, Hôpital la Timone, AP-HM, 13005 Marseille, France;
- Aix-Marseille Université, 27 Boulevard Jean Moulin, 13385 Marseille, France
| | - Pauline Brige
- Aix Marseille Université, LIIE, 13007 Marseille, France; (O.L.); (V.V.); (E.G.); (P.B.)
- Aix Marseille Université, CERIMED, 13007 Marseille, France; (S.B.); (L.B.); (M.B.); (B.G.)
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Guo J, Sanchez-Vivaldi JA, Patel MS, Wang BK, Shubin AD, Kadakia Y, Shah JA, MacConmara M, Hanish S, Vagefi PA, Hwang CS. Abnormal Liver Biopsies of Donor Grafts in Pediatric Liver Transplantation: How Do They Fare? Ann Transplant 2024; 29:e944245. [PMID: 39104079 PMCID: PMC11316410 DOI: 10.12659/aot.944245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Accepted: 04/19/2024] [Indexed: 08/07/2024] Open
Abstract
BACKGROUND Little is known about outcomes of pediatric patients transplanted using donor liver grafts with abnormal biopsy results. We assessed donor liver biopsy data to report characteristics and outcomes of abnormal livers transplanted in pediatric patients. MATERIAL AND METHODS We identified pediatric patients who received a liver transplant from a biopsied deceased donor between 2015 and 2022 using the national database UNOS Standard Transplant Analysis and Research files. Recipients were excluded if they received multi-organ transplants or were lost to follow-up. Livers with ≤5% macrosteatosis, no fibrosis, and no inflammation were classified as normal livers (NL). Allografts with >5% macrosteatosis, any fibrosis, or any inflammation were considered abnormal livers (AL). Donor and recipient demographic data and outcomes were examined. RESULTS Of the 3808 total pediatric liver transplants in the study period, there were 213 biopsied donor liver allografts transplanted into pediatric recipients. Of those, 114 were NL and 99 were AL. 35.4% (35/99) of the AL had >5% macrosteatosis with a mean of 7.6±11.4%, 64.6% (64/99) had any inflammation, and 18.2% (18/99) had any fibrosis. AL donors were significantly older than NL donors. AL recipients had higher PELD scores. There were no significant differences in length of stay, rejection rates and causes, or allograft survival between AL and NL. Multivariable analysis revealed that inflammation was independently associated with a significantly greater risk for graft failure. CONCLUSIONS Outcomes of abnormal livers are excellent. Inflammation was an independent risk factor for poor graft prognosis. Donor biopsies in pediatric liver transplantation can be a useful adjunct to assess outcomes.
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Affiliation(s)
- Jason Guo
- University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Jorge A. Sanchez-Vivaldi
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Division of Pediatric Transplantation, Children’s Medical Center, Dallas, TX, USA
| | - Madhukar S. Patel
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Division of Pediatric Transplantation, Children’s Medical Center, Dallas, TX, USA
| | - Benjamin K. Wang
- University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Andrew D. Shubin
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Division of Pediatric Transplantation, Children’s Medical Center, Dallas, TX, USA
| | - Yash Kadakia
- University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Jigesh A. Shah
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Division of Pediatric Transplantation, Children’s Medical Center, Dallas, TX, USA
| | - Malcolm MacConmara
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Division of Pediatric Transplantation, Children’s Medical Center, Dallas, TX, USA
- TransMedics, Andover, MA, USA
| | - Steven Hanish
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Division of Pediatric Transplantation, Children’s Medical Center, Dallas, TX, USA
| | - Parsia A. Vagefi
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Division of Pediatric Transplantation, Children’s Medical Center, Dallas, TX, USA
| | - Christine S. Hwang
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Division of Pediatric Transplantation, Children’s Medical Center, Dallas, TX, USA
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Campsen J, Poole C. CT-Based Hounsfield Units for Pre-donation Liver Steatosis Assessment: Enhancing Transplant Outcomes and Efficiency. Cureus 2024; 16:e61196. [PMID: 38939256 PMCID: PMC11208326 DOI: 10.7759/cureus.61196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/27/2024] [Indexed: 06/29/2024] Open
Abstract
Steatotic liver grafts are associated with increased post-transplant complications and graft failure. The field of transplantation faces a challenge in the absence of a reliable pre-donation protocol for quantitatively assessing steatosis in cadaveric liver grafts. Current pre-donation evaluation protocols often involve non-contrast computed tomography (CT) scans of the chest and/or abdomen as an initial step in organ donation assessment. These routine scans have the potential to identify and quantify hepatic fat content when more than 20% of the liver parenchyma is affected. By incorporating both abdominal and thoracic CT scans during the donor workup, an assessment of the quality of the liver and spleen can be achieved. Our study is based on the hypothesis that a precise pre-donation evaluation utilizing Hounsfield units (HU) derived from CT images of the liver and spleen can provide transplant programs with crucial data regarding the extent of steatosis. This approach is envisioned as a significant advancement that could potentially eliminate the need for preoperative liver biopsies by offering essential information to streamline the evaluation process.
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Affiliation(s)
- Jeffrey Campsen
- Surgery, University of Utah School of Medicine, Salt Lake City, USA
- Organ Procurement Organization, Donor Connect, Salt Lake City, USA
| | - Carrie Poole
- Organ Procurement Organization, Donor Connect, Salt Lake City, USA
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Tian X, Wu L, Li X, Zheng W, Zuo H, Song H. Exosomes derived from bone marrow mesenchymal stem cells alleviate biliary ischemia reperfusion injury in fatty liver transplantation by inhibiting ferroptosis. Mol Cell Biochem 2024; 479:881-894. [PMID: 37243945 PMCID: PMC11016128 DOI: 10.1007/s11010-023-04770-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 05/15/2023] [Indexed: 05/29/2023]
Abstract
Fatty liver grafts are susceptible to ischemia reperfusion injury (IRI), increasing the risk of biliary complications after liver transplantation (LT). Ferroptosis, a newly recognized programmed cell death, is expected to be a novel therapeutic target for IRI. We investigated whether exosomes derived from heme oxygenase 1-modified bone marrow mesenchymal stem cells (HExos) relieve ferroptosis and protect biliary tracts from IRI in a rat fatty liver transplantation model. Rats were fed with a methionine choline deficient (MCD) diet for 2 weeks to induce severe hepatic steatosis. Steatotic grafts were implanted and HExos were administered after liver transplantation. A series of functional assays and pathological analysis were performed to assess ferroptosis and biliary IRI. The HExos attenuated IRI following liver transplantation, as demonstrated by less ferroptosis, improved liver function, less Kupffer and T cell activation, and less long-term biliary fibrosis. MicroRNA (miR)-204-5p delivered by HExos negatively regulated ferroptosis by targeting a key pro-ferroptosis enzyme, ACSL4. Ferroptosis contributes to biliary IRI in fatty liver transplantation. HExos protect steatotic grafts by inhibiting ferroptosis, and may become a promising strategy to prevent biliary IRI and expand the donor pool.
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Affiliation(s)
- Xuan Tian
- School of Medicine, Nankai University, Tianjin, People's Republic of China
| | - Longlong Wu
- School of Medicine, Nankai University, Tianjin, People's Republic of China
| | - Xiang Li
- Tianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin, 300070, People's Republic of China
| | - Weiping Zheng
- Department of Organ Transplantation, Tianjin First Central Hospital, School of Medicine, Nankai University, No. 24 Fukang Road, Nankai District, Tianjin, 300192, People's Republic of China
- NHC Key Laboratory of Critical Care Medicine, Tianjin, 300192, People's Republic of China
| | - Huaiwen Zuo
- Tianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin, 300070, People's Republic of China
| | - Hongli Song
- Department of Organ Transplantation, Tianjin First Central Hospital, School of Medicine, Nankai University, No. 24 Fukang Road, Nankai District, Tianjin, 300192, People's Republic of China.
- Tianjin Key Laboratory of Organ Transplantation, Tianjin, People's Republic of China.
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5
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Klinkachorn M, Tsoi-A-Sue C, Narayan RR, Kadri H, Tam T, Melcher ML. Development of a portable device to quantify hepatic steatosis in potential donor livers. FRONTIERS IN TRANSPLANTATION 2023; 2:1206085. [PMID: 38993883 PMCID: PMC11235317 DOI: 10.3389/frtra.2023.1206085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 06/08/2023] [Indexed: 07/13/2024]
Abstract
An accurate estimation of liver fat content is necessary to predict how a donated liver will function after transplantation. Currently, a pathologist needs to be available at all hours of the day, even at remote hospitals, when an organ donor is procured. Even among expert pathologists, the estimation of liver fat content is operator-dependent. Here we describe the development of a low-cost, end-to-end artificial intelligence platform to evaluate liver fat content on a donor liver biopsy slide in real-time. The hardware includes a high-resolution camera, display, and GPU to acquire and process donor liver biopsy slides. A deep learning model was trained to label and quantify fat globules in liver tissue. The algorithm was deployed on the device to enable real-time quantification and characterization of fat content for transplant decision-making. This information is displayed on the device and can also be sent to a cloud platform for further analysis.
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Affiliation(s)
- Mac Klinkachorn
- Department of Engineering, Stanford University, Stanford, CA, United States
| | | | - Raja R. Narayan
- Department of Surgery, Mass General, Boston MA, United States
| | - Haaris Kadri
- Department of Surgery, Stanford University, Stanford, CA, United States
| | - Taylor Tam
- Menlo School, Menlo Park, CA, United States
| | - Marc L. Melcher
- Department of Surgery, Stanford University, Stanford, CA, United States
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Rajamani AS, Shamlee JK, Rammohan A, Sai VVR, Rela M. Diffuse Reflectance Spectroscopy for The Assessment of Steatosis in Liver Phantom and Liver Donors - A Pilot Study. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2022; 2022:3003-3006. [PMID: 36086423 DOI: 10.1109/embc48229.2022.9871515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
This paper reports the application of a low-cost diagnostic modality for fat analysis in a liver phantom as well as human liver donors. The device works on the principle of diffuse reflectance spectroscopy, which absorbs and/or scatters depending upon the molecules that compose a tissue. Here, we describe the development of liver phantom of varying fat concentration using saturated fat mimicking liver steatosis. Followed by a pilot study in the human liver donor setting. Later, handheld device based on Infrared-LED and Photodetector for real-time time assessment of live donor liver and fat assessment. Clinical Relevance- This device can be used in the development of an accurate and non-invasive for quantification of liver fat in the deceased donor selection process. It has an error margin of 10% in the quantification of fat which is comparable to a standard biopsy technique.
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Gedallovich SM, Ladner DP, VanWagner LB. Liver transplantation in the era of non-alcoholic fatty liver disease/metabolic (dysfunction) associated fatty liver disease: the dilemma of the steatotic liver graft on transplantation and recipient survival. Hepatobiliary Surg Nutr 2022; 11:425-429. [PMID: 35693416 PMCID: PMC9186195 DOI: 10.21037/hbsn-22-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Accepted: 03/07/2022] [Indexed: 01/10/2025]
Affiliation(s)
- Seren M. Gedallovich
- Division of Palliative Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Daniela P. Ladner
- Division of Organ Transplantation, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Lisa B. VanWagner
- Division of Gastroenterology & Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
- Division of Epidemiology, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
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Choi J, Choi Y, Hong SY, Suh S, Hong K, Han ES, Lee JM, Hong SK, Yi NJ, Lee KW, Suh KS. Changes in Indices of Steatosis and Fibrosis in Liver Grafts of Living Donors After Weight Reduction. Front Surg 2022; 9:827526. [PMID: 35592121 PMCID: PMC9110767 DOI: 10.3389/fsurg.2022.827526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 03/28/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundA short-term weight reduction program for potential living donors was introduced to reduce the extent of hepatic steatosis prior to liver transplantation. We aimed to investigate changes in non-invasive hepatic steatosis and fibrosis indices among those who completed the program.MethodsAmong 1,950 potential living liver donors between January 2011 and May 2019, 160 living donors joined the weight reduction program. The prospectively collected clinical data of these potential liver donors were analyzed retrospectively. Hepatic steatosis and fibrosis scores were determined using the fatty liver index (FLI), hepatic steatosis index (HSI), and NAFLD fibrosis score (NFS) and compared to MR spectroscopy (MRS) fat fraction results before and after weight reduction.ResultsThirty-nine potential living donors who had undergone MRS both before and after weight reduction were included in the analysis. Their body weight decreased from 78.02 ± 10.89 kg to 72.36 ± 10.38 kg over a mean of 71.74 ± 58.11 days. FLI, HSI, and MRS values decreased significantly from 41.52 ± 19.05 to 24.53 ± 15.93, 39.64 ± 3.74 to 35.06 ± 3.82, and 12.20 ± 4.05 to 6.24 ± 3.36, respectively. No significant decreases in NFS were observed. There was a significant correlation between the extent of HSI change and the extent of MRS change (R2 value = 0.69, P < 0.001), although there was no correlation between MRS and FLI.ConclusionThe weight reduction program significantly improved non-invasive indices of hepatic steatosis over a short period. HSI may allow for prediction of simple decreases in hepatic steatosis.
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Fodor M, Woerdehoff A, Peter W, Esser H, Oberhuber R, Margreiter C, Maglione M, Cardini B, Resch T, Weissenbacher A, Sucher R, Zoller H, Tilg H, Öfner D, Schneeberger S. Reassessment of Relevance and Predictive Value of Parameters Indicating Early Graft Dysfunction in Liver Transplantation: AST Is a Weak, but Bilirubin and INR Strong Predictors of Mortality. Front Surg 2021; 8:693288. [PMID: 34869549 PMCID: PMC8634944 DOI: 10.3389/fsurg.2021.693288] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Accepted: 10/27/2021] [Indexed: 01/14/2023] Open
Abstract
Introduction: Early graft dysfunction (EAD) complicates liver transplantation (LT). The aim of this analysis was to discriminate between the weight of each variable as for its predictive value toward patient and graft survival. Methods: We reviewed all LT performed at the Medical University of Innsbruck between 2007 and 2018. EAD was recorded when one of the following criteria was present: (i) aspartate aminotransferase (AST) levels >2,000 IU/L within the first 7 days, (ii) bilirubin levels ≥10mg/dL or (iii) international normalized ratio (INR) ≥1.6 on postoperative day 7. Results: Of 616 LT, 30.7% developed EAD. Patient survival did not differ significantly (P = 0.092; log rank-test = 2.87), graft survival was significantly higher in non-EAD patients (P = 0.008; log rank-test = 7.13). Bilirubin and INR on postoperative day 7 were identified as strong mortality predictors (Bilirubin HR = 1.71 [1.34, 2.16]; INR HR = 2.69 [0.51, 14.31]), in contrast to AST (HR = 0.91 [0.75, 1.10]). Similar results were achieved for graft loss estimation. A comparison with the Model for Early Allograft Function (MEAF) and the Liver Graft Assessment Following Transplantation (L-GrAFT) score identified a superior discrimination potential but lower specificity. Conclusion: Contrarily to AST, bilirubin and INR have strong predictive capacity for patient and graft survival. This fits well with the understanding, that bile duct injury and deprivation of synthetic function rather than hepatocyte injury are key factors in LT.
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Affiliation(s)
- Margot Fodor
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Adriana Woerdehoff
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Wolfgang Peter
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Hannah Esser
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Rupert Oberhuber
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Christian Margreiter
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Manuel Maglione
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Benno Cardini
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Thomas Resch
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Annemarie Weissenbacher
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Robert Sucher
- Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig, Leipzig, Germany
| | - Heinz Zoller
- Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria
| | - Herbert Tilg
- Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria
| | - Dietmar Öfner
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Stefan Schneeberger
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
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Peltec A, Hotineanu A, Popescu I, Braşoveanu V. The impact of liver steatosis on the postoperative evolution after right lobe living-donor hepatectomy. Med Pharm Rep 2021; 94:S43-S50. [PMID: 38912410 PMCID: PMC11188031 DOI: 10.15386/mpr-2512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Living donor liver transplantation has become a feasible treatment modality for end-stage liver disease. The obesity epidemic worldwide has made it increasingly common to encounter liver steatosis in living donor candidates. The aim of study was to analyze the impact of moderate hepatic steatosis on the postoperative evolutions after right lobe living-donor hepatectomy. METHODS Living donors who underwent donor hepatectomy during the period 2000 to 2020 in two medical centers were included in this study. We distinguished 3 groups based on the degree of steatosis: Group O - 0%, Group I - 1-10% and Group II >10%. RESULTS A total number of 157 living donors underwent surgery, of whom 112 (71.34%) were right lobe liver donors. There were 62 without steatosis, 31 - with steatosis 1-10% and 19 with steatosis >10%. No difference has been found in proportion of men, median of age, body mass index and left lobe/total liver volume ration in compared groups. Total liver volume was significantly higher in the Group I than in the Group O (p=0.028). The moderate hepatic steatosis (HS) group presented significant higher volume of intraoperative hemorrhage than no-HS group (p=0.041). No differences were observed in the postoperative liver function between the groups. The minimal HS group comprised a significantly higher proportion of postoperative complications than no-HS group (67.7% vs 40.3%, p=0.043). The longer postoperative length of hospital stay in ICU was observed in Group I than in Group O (p=0.024). CONCLUSION Moderate HS does not importantly impair living liver donors' safety.
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Affiliation(s)
- Angela Peltec
- Discipline of Gastroenterology, Department of Internal Medicine, Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Moldova
| | - Adrian Hotineanu
- Department of Surgery No. 2, Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Moldova
| | - Irinel Popescu
- Department of Hepatobiliary Surgery and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania
| | - Vladislav Braşoveanu
- Department of Hepatobiliary Surgery and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania
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11
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Rajamani AS, Rammohan A, Sai VVR, Rela M. Non-invasive real-time assessment of hepatic macrovesicular steatosis in liver donors: Hypothesis, design and proof-of-concept study. World J Hepatol 2021; 13:1208-1214. [PMID: 34786162 PMCID: PMC8568585 DOI: 10.4254/wjh.v13.i10.1208] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 04/18/2021] [Accepted: 09/17/2021] [Indexed: 02/06/2023] Open
Abstract
Macrovesicular Steatosis (MS) is an independent risk factor for adverse post-liver transplant (LT) outcomes. The degree of MS is intimately related to the viability of the liver graft, which in turn is crucial to the success of the operation. An ideal liver graft should have no MS and most centres would find it unacceptable to use a donor liver with severe MS for LT. While a formal liver biopsy is the gold-standard diagnostic test for MS, given the logistical and time constraints it is not universally feasible. Other tests like a frozen section biopsy are plagued by issues of fallibility with reporting and sampling bias making them inferior to a liver biopsy. Hence, the development of an accurate, non-invasive, easy-to-use, handheld, real-time device for quantification of MS would fill this lacuna in the deceased donor selection process. We present the hypothesis, design and proof-of-concept of a study, which aims to standardise and determine the feasibility and accuracy of a novel handheld device applying the principle of diffuse reflectance spectroscopy for real-time quantification of MS.
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Affiliation(s)
- Allwyn S Rajamani
- Department of Applied Mechanics, Indian Institute of Technology Madras, Chennai 600036, India
| | - Ashwin Rammohan
- Institute of Liver Disease and Transplantation, Dr. Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai 600044, India
| | - VV Raghavendra Sai
- Department of Applied Mechanics, Indian Institute of Technology Madras, Chennai 600036, India
| | - Mohamed Rela
- Institute of Liver Disease and Transplantation, Dr. Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai 600044, India
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12
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Hsu PK, Wu LS, Su WW, Su PY, Chen YY, Hsu YC, Yen HH, Wu CL. Comparing the controlled attenuation parameter using FibroScan and attenuation imaging with ultrasound as a novel measurement for liver steatosis. PLoS One 2021; 16:e0254892. [PMID: 34653177 PMCID: PMC8519468 DOI: 10.1371/journal.pone.0254892] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 07/06/2021] [Indexed: 12/19/2022] Open
Abstract
Background/Aims In a recent study, attenuation imaging (ATI) with ultrasound was used as a new approach for detecting liver steatosis. However, although there are many studies on ATI and controlled attenuation parameter (CAP) that prove their practicability, there are few studies comparing these two methods. As such, this study compared CAP and ATI for the detection and evaluation of liver steatosis. Methods A prospective analysis of 28 chronic liver disease patients who underwent liver biopsy, FibroScan® imaging, and ATI with ultrasound was conducted. The presence and degree of steatosis, as measured with the FibroScan® device and ATI, were compared with the pathological results obtained using liver biopsy. Results The areas under the receiver operating characteristic curve (AUROC) of ATI and CAP for differentiating between normal and hepatic steatosis were 0.97 (95% confidence interval [CI] 0.83–1.00) and 0.96 (95% CI 0.81–0.99), respectively. ATI has a higher AUROC than CAP does in liver steatosis, at 0.99 (95% CI, 0.86–1.00) versus 0.91 (95% CI, 0.74–0.98) in grade ≥ 2 and 0.97 (95% CI, 0.82–1.00) versus 0.88 (95% CI, 0.70–0.97) in grade = 3, respectively. Conclusion The ATI and CAP results showed good consistency and accuracy for the steatosis grading when compared with the liver biopsy results. Moreover, ATI is even better than CAP in patients with moderate or severe steatosis. Therefore, ATI represents a non-invasive and novel diagnostic tool with which to support the diagnosis of liver steatosis in clinical practice.
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Affiliation(s)
- Po-Ke Hsu
- Department of Gastroenterology, Changhua Christian Hospital, Changhua County, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Li-Sha Wu
- Department of Ultrasound, Changhua Christian Hospital, Changhua County, Taiwan
| | - Wei-Wen Su
- Department of Gastroenterology, Changhua Christian Hospital, Changhua County, Taiwan
| | - Pei-Yuan Su
- Department of Gastroenterology, Changhua Christian Hospital, Changhua County, Taiwan
| | - Yang-Yuan Chen
- Department of Gastroenterology, Changhua Christian Hospital, Changhua County, Taiwan
| | - Yu-Chun Hsu
- Department of Gastroenterology, Changhua Christian Hospital, Changhua County, Taiwan
| | - Hsu-Heng Yen
- Department of Gastroenterology, Changhua Christian Hospital, Changhua County, Taiwan
| | - Chia-Lin Wu
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Department of Nephrology, Changhua Christian Hospital, Changhua County, Taiwan
- * E-mail:
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13
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Chen M, Chen Z, Lin X, Hong X, Ma Y, Huang C, He X, Ju W. Application of ischaemia-free liver transplantation improves prognosis of patients with steatotic donor livers - a retrospective study. Transpl Int 2021; 34:1261-1270. [PMID: 33484201 PMCID: PMC8361689 DOI: 10.1111/tri.13828] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 12/21/2020] [Accepted: 01/19/2021] [Indexed: 12/20/2022]
Abstract
The use of steatotic livers in liver transplantation (LT) is controversial. Ischaemia‐free liver transplantation (IFLT) has obvious advantages for the recovery of allograft function. The aim of this study was to examine the effect of liver grafts with steatosis on outcome and the effect of IFLT with steatotic livers. 360 patients with LT were enrolled in this study. Perioperative characteristics and differences in outcome among different grades of steatotic groups, and between the IFLT and conventional LT (CLT) groups were analysed. Occurrence of early allograft dysfunction (EAD; 50%) and primary nonfunction (PNF; 20%) was significantly higher in the severe steatosis group (P < 0.001 and <0.001, respectively). Survival rate is significantly low in severe steatosis group (3‐year: 60%, P = 0.0039). The IFLT group had a significantly lower occurrence of EAD than the CLT group (0% vs. 60%, P = 0.01). The level of postoperative peak AST, GGT and creatine were significantly lower in IFLT group (P = 0.009, 0.032 and 0.024, respectively). In multivariable analysis, IFLT and EAD were independent factors affecting postoperative survival. Severe steatotic livers lead to severe complications and poor outcomes in LT. IFLT has obvious advantages for reducing the rate of EAD in LT with steatotic livers.
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Affiliation(s)
- Maogen Chen
- Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Zhitao Chen
- Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Xiaohong Lin
- Division of General Surgery, The Eastern Hospital of the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xitao Hong
- Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Yihao Ma
- Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Changjun Huang
- Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Xiaoshun He
- Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Weiqiang Ju
- Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
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14
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Yang DJ, Shi JH, Xia ZP, Guo WZ, Ahmed MS, Zhang SJ. Hepatic connective tissue growth factor expression and regulation differ between non-steatotic and non-alcoholic steatotic livers from brain-dead donor. Sci Rep 2021; 11:3857. [PMID: 33594198 PMCID: PMC7886893 DOI: 10.1038/s41598-021-83516-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 02/04/2021] [Indexed: 11/09/2022] Open
Abstract
Accurate evaluation of liver steatosis is required from brain-dead donors (BDDs) with nonalcoholic fatty liver disease (NAFLD). Our purposes were to investigate expression and regulation of connective tissue growth factor (CTGF) expression in livers from human and rat after brain death, and further evaluate its potential application. NAFLD and brain death models were established in rats. LX2 cells were cultured under hypoxia/reoxygenation. CTGF protein and mRNA levels were measured in liver samples from BDDs of human and rat by immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. YAP-regulated CTGF expression was investigated in LX2 cells via YAP small interfering RNA and Verteporfin treatment. Blood CTGF level from BDDs was measured by enzyme-linked immunosorbent assay. After brain death, CTGF, transforming growth factor-β and YAP were overexpressed in non-alcoholic steatotic liver, whereas CTGF was downregulated in non-steatotic liver. Time-series analysis revealed that CTGF and YAP expression was comparable, as confirmed by inhibited YAP expression in LX2 cells. CTGF level and NAFLD activity were linearly correlated. CTGF expression and regulation differ between non-steatosis and nonalcoholic steatosis livers from BDDs. CTGF may be an important factor to evaluate graft quality from BDDs with NAFLD.
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Affiliation(s)
- Dong-Jing Yang
- Department of Hepatobiliary and Pancreatic Surgery, Henan Key Laboratory of Digestive Organ Transplantation and Zhengzhou Key Laboratory for HPB Diseases and Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China
| | - Ji-Hua Shi
- Department of Hepatobiliary and Pancreatic Surgery, Henan Key Laboratory of Digestive Organ Transplantation and Zhengzhou Key Laboratory for HPB Diseases and Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China
| | - Zong-Ping Xia
- Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China
| | - Wen-Zhi Guo
- Department of Hepatobiliary and Pancreatic Surgery, Henan Key Laboratory of Digestive Organ Transplantation and Zhengzhou Key Laboratory for HPB Diseases and Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China
| | - Mohammed Shakil Ahmed
- Institute for Surgical Research, Department of Cardiology and Center for Heart Failure Research, Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway
| | - Shui-Jun Zhang
- Department of Hepatobiliary and Pancreatic Surgery, Henan Key Laboratory of Digestive Organ Transplantation and Zhengzhou Key Laboratory for HPB Diseases and Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
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15
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Michelotto J, Gassner JMGV, Moosburner S, Muth V, Patel MS, Selzner M, Pratschke J, Sauer IM, Raschzok N. Ex vivo machine perfusion: current applications and future directions in liver transplantation. Langenbecks Arch Surg 2021; 406:39-54. [PMID: 33216216 PMCID: PMC7870621 DOI: 10.1007/s00423-020-02014-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 07/21/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND Liver transplantation is the only curative treatment option for end-stage liver disease; however, its use remains limited due to a shortage of suitable organs. In recent years, ex vivo liver machine perfusion has been introduced to liver transplantation, as a means to expand the donor organ pool. PURPOSE To present a systematic review of prospective clinical studies on ex vivo liver machine perfusion, in order to assess current applications and highlight future directions. METHODS A systematic literature search of both PubMed and ISI web of science databases as well as the ClinicalTrials.gov registry was performed. RESULTS Twenty-one articles on prospective clinical trials on ex vivo liver machine perfusion were identified. Out of these, eight reported on hypothermic, eleven on normothermic, and two on sequential perfusion. These trials have demonstrated the safety and feasibility of ex vivo liver machine perfusion in both standard and expanded criteria donors. Currently, there are twelve studies enrolled in the clinicaltrials.gov registry, and these focus on use of ex vivo perfusion in extended criteria donors and declined organs. CONCLUSION Ex vivo liver machine perfusion seems to be a suitable strategy to expand the donor pool for liver transplantation and holds promise as a platform for reconditioning diseased organs.
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Affiliation(s)
- Julian Michelotto
- Charité - Universitätsmedizin Berlin, Department of Surgery, Experimental Surgery, corporate member of Freie Universität Berlin, Humboldt- Universität zu Berlin and Berlin Institute of Health, Campus Charité Mitte | Campus Virchow-Klinikum, Berlin, Germany
| | - Joseph M G V Gassner
- Charité - Universitätsmedizin Berlin, Department of Surgery, Experimental Surgery, corporate member of Freie Universität Berlin, Humboldt- Universität zu Berlin and Berlin Institute of Health, Campus Charité Mitte | Campus Virchow-Klinikum, Berlin, Germany
| | - Simon Moosburner
- Charité - Universitätsmedizin Berlin, Department of Surgery, Experimental Surgery, corporate member of Freie Universität Berlin, Humboldt- Universität zu Berlin and Berlin Institute of Health, Campus Charité Mitte | Campus Virchow-Klinikum, Berlin, Germany
| | - Vanessa Muth
- Charité - Universitätsmedizin Berlin, Department of Surgery, Experimental Surgery, corporate member of Freie Universität Berlin, Humboldt- Universität zu Berlin and Berlin Institute of Health, Campus Charité Mitte | Campus Virchow-Klinikum, Berlin, Germany
| | - Madhukar S Patel
- Department of Surgery, Abdominal Transplant and HPB Surgery, Ajmera Family Transplant Centre, Toronto General Hospital, Toronto, ON, Canada
| | - Markus Selzner
- Department of Surgery, Abdominal Transplant and HPB Surgery, Ajmera Family Transplant Centre, Toronto General Hospital, Toronto, ON, Canada
| | - Johann Pratschke
- Charité - Universitätsmedizin Berlin, Department of Surgery, Experimental Surgery, corporate member of Freie Universität Berlin, Humboldt- Universität zu Berlin and Berlin Institute of Health, Campus Charité Mitte | Campus Virchow-Klinikum, Berlin, Germany
| | - Igor M Sauer
- Charité - Universitätsmedizin Berlin, Department of Surgery, Experimental Surgery, corporate member of Freie Universität Berlin, Humboldt- Universität zu Berlin and Berlin Institute of Health, Campus Charité Mitte | Campus Virchow-Klinikum, Berlin, Germany
| | - Nathanael Raschzok
- Charité - Universitätsmedizin Berlin, Department of Surgery, Experimental Surgery, corporate member of Freie Universität Berlin, Humboldt- Universität zu Berlin and Berlin Institute of Health, Campus Charité Mitte | Campus Virchow-Klinikum, Berlin, Germany.
- Department of Surgery, Abdominal Transplant and HPB Surgery, Ajmera Family Transplant Centre, Toronto General Hospital, Toronto, ON, Canada.
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16
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Baidya R, Crawford DHG, Gautheron J, Wang H, Bridle KR. Necroptosis in Hepatosteatotic Ischaemia-Reperfusion Injury. Int J Mol Sci 2020; 21:ijms21165931. [PMID: 32824744 PMCID: PMC7460692 DOI: 10.3390/ijms21165931] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 08/12/2020] [Accepted: 08/12/2020] [Indexed: 02/07/2023] Open
Abstract
While liver transplantation remains the sole treatment option for patients with end-stage liver disease, there are numerous limitations to liver transplantation including the scarcity of donor livers and a rise in livers that are unsuitable to transplant such as those with excess steatosis. Fatty livers are susceptible to ischaemia-reperfusion (IR) injury during transplantation and IR injury results in primary graft non-function, graft failure and mortality. Recent studies have described new cell death pathways which differ from the traditional apoptotic pathway. Necroptosis, a regulated form of cell death, has been associated with hepatic IR injury. Receptor-interacting protein kinase 3 (RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL) are thought to be instrumental in the execution of necroptosis. The study of hepatic necroptosis and potential therapeutic approaches to attenuate IR injury will be a key factor in improving our knowledge regarding liver transplantation with fatty donor livers. In this review, we focus on the effect of hepatic steatosis during liver transplantation as well as molecular mechanisms of necroptosis and its involvement during liver IR injury. We also discuss the immune responses triggered during necroptosis and examine the utility of necroptosis inhibitors as potential therapeutic approaches to alleviate IR injury.
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Affiliation(s)
- Raji Baidya
- Faculty of Medicine, The University of Queensland, Brisbane, Queensland QLD 4006, Australia; (R.B.); (D.H.G.C.)
- Gallipoli Medical Research Institute, Brisbane, Queensland QLD 4120, Australia;
| | - Darrell H. G. Crawford
- Faculty of Medicine, The University of Queensland, Brisbane, Queensland QLD 4006, Australia; (R.B.); (D.H.G.C.)
- Gallipoli Medical Research Institute, Brisbane, Queensland QLD 4120, Australia;
| | - Jérémie Gautheron
- Sorbonne University, Inserm, Centre de Recherche Saint-Antoine (CRSA), 75012 Paris, France;
- Institute of Cardiometabolism and Nutrition (ICAN), 75013 Paris, France
| | - Haolu Wang
- Gallipoli Medical Research Institute, Brisbane, Queensland QLD 4120, Australia;
- Diamantina Institute, The University of Queensland, Brisbane, Queensland QLD 4102, Australia
| | - Kim R. Bridle
- Faculty of Medicine, The University of Queensland, Brisbane, Queensland QLD 4006, Australia; (R.B.); (D.H.G.C.)
- Gallipoli Medical Research Institute, Brisbane, Queensland QLD 4120, Australia;
- Correspondence: ; Tel.: +61-7-3346-0698
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17
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Samji NS, Heda R, Satapathy SK. Peri-transplant management of nonalcoholic fatty liver disease in liver transplant candidates . Transl Gastroenterol Hepatol 2020; 5:10. [PMID: 32190778 PMCID: PMC7061181 DOI: 10.21037/tgh.2019.09.09] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Accepted: 09/23/2019] [Indexed: 12/12/2022] Open
Abstract
The incidence of non-alcoholic fatty liver disease (NAFLD) is rapidly growing, affecting 25% of the world population. Non-alcoholic steatohepatitis (NASH) is the most severe form of NAFLD and affects 1.5% to 6.5% of the world population. Its rising incidence will make end-stage liver disease (ESLD) due to NASH the number one indication for liver transplantation (LT) in the next 10 to 20 years, overtaking Hepatitis C. Patients with NASH also have a high prevalence of associated comorbidities such as type 2 diabetes, obesity, metabolic syndrome, cardiovascular disease, and chronic kidney disease (CKD), which must be adequately managed during the peritransplant period for optimal post-transplant outcomes. The focus of this review article is to provide a comprehensive overview of the unique challenges these patients present in the peritransplant period, which comprises the pre-transplant, intraoperative, and immediate postoperative periods.
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Affiliation(s)
- Naga Swetha Samji
- Tennova Cleveland Hospital, 2305 Chambliss Ave NW, Cleveland, TN, USA
| | - Rajiv Heda
- University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA
| | - Sanjaya K. Satapathy
- Division of Hepatology and Sandra Atlas Bass Center for Liver Diseases, Northwell Health, Manhasset, NY, USA
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