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Cui LL, Zhang L, Liu S, Zhu Q, Xue FS. Dexmedetomidine Cannot Attenuate Liver Injury and Improve Outcomes Following Laparoscopic Living Donor Hepatectomy: A Randomised Controlled Trial. Drug Des Devel Ther 2025; 19:4263-4274. [PMID: 40420947 PMCID: PMC12105671 DOI: 10.2147/dddt.s524343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2025] [Accepted: 05/15/2025] [Indexed: 05/28/2025] Open
Abstract
Purpose To determine the effects of intraoperative dexmedetomidine (DEX) administration on postoperative ischaemia/reperfusion injury (HIRI) and clinical outcomes of patients undergoing the laparoscopic living donor hepatectomy (LLDH). Patients and Methods Fifty-five patients who underwent the LLDH were randomly assigned to the DEX or control group. The DEX group received an intravenous infusion of DEX with an bolus dose of 1 µg/kg for 15 min before anaesthesia induction, followed by a continuous infusion at a rate of 0.4 µg/kg/h until the portal branch was disconnected. The control group was given an intravenous infusion of 0.9% saline at same volume and rate. The primary outcome was peak serum aspartate aminotransferase (AST) level during the first 72 h postoperatively. The secondary outcomes included other variables of postoperative liver and kidney function, intraoperative hemodynamic changes, postoperative recovery outcomes and the occurrence of complications. Results The peak serum AST level during the first 72 h postoperatively was not significantly different between groups (DEX vs control: 288 [194-466] vs 324 [194-437] IU/L; difference, -1.2 IU/L; 95% CI, -86.9 to 88.0; P=0.973). The intraoperative mean artery pressure was not significantly different, but intraoperative heart rate was significantly decreased in the DEX group. There were no significant differences between groups in other secondary outcomes. Conclusion This study demonstrates that intraoperative DEX administration at the studied dosage regimens cannot attenuate postoperative HIRI and does not improve clinical outcomes in patients undergoing the LLDH. Clinical Trial Registration www.chictr.org.cn, ChiCTR2000040629.
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Affiliation(s)
- Ling-Li Cui
- Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Liang Zhang
- Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Shen Liu
- Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Qian Zhu
- Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Fu-Shan Xue
- Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China
- Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, Fuzhou, People’s Republic of China
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Liu G, Tang F, Wang T, Yan JQ, Li FH, Ha FS, Zhang X, Jing L, Liang J. Efficacy of recombinant human thrombopoietin in patients with acute-on-chronic liver failure and thrombocytopenia: A prospective, open-label study. World J Gastroenterol 2025; 31:105004. [PMID: 40248371 PMCID: PMC12001200 DOI: 10.3748/wjg.v31.i14.105004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 02/24/2025] [Accepted: 03/24/2025] [Indexed: 04/11/2025] Open
Abstract
BACKGROUND Patients with acute-on-chronic liver failure (ACLF) have a high mortality rate, poor prognosis, and often experience concurrent thrombocytopenia and bleeding events. AIM To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) in patients with ACLF with concomitant severe thrombocytopenia. METHODS This was a prospective, open-label study. We assigned 70 ACLF patients with severe thrombocytopenia into the rhTPO group and control group, with 35 patients in each group. Patients in the rhTPO group received subcutaneous injections of rhTPO at a dose of 15000 IU/day for 7 consecutive days, while patients in the control group did not receive rhTPO treatment. The primary endpoint was the proportion of patients with platelet count > 50 × 109/L on day 14. RESULTS The proportion of patients with platelet count > 50 × 109/L on day 14 was 60.7% in the rhTPO group, which was significantly higher than that (12.0%) in the control group (P < 0.001). The platelet count in the rhTPO group on day 14 was 64 × 109/L, exceeding the baseline of 28 × 109/L. Compared to the control group, the rhTPO group exhibited a significant increase in platelet count from baseline (P < 0.05). Model for end-stage liver disease score, albumin level and international normalized ratio improved significantly from baseline on day 14 after rhTPO injection. The concentrations of serum thrombopoietin and hepatocyte growth factor in the rhTPO group after 7 days were 143.7 and 195.4 pg/mL, respectively, showing a significant increase from baseline (P < 0.05). Eight (22.9%) patients had bleeding events in the control group compared with four (11.4%) in the rhTPO group. The incidence of 90-day mortality was also higher in the control group (6, 17.1%) than that in the rhTPO group (3, 8.6%). CONCLUSION rhTPO significantly increased the platelet count in ACLF patients with thrombocytopenia and reduce the occurrence of bleeding events, with a good safety profile.
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Affiliation(s)
- Gang Liu
- Department of Internal Medicine, The Third Central Clinical College of Tianjin Medical University, Tianjin 300300, China
- Department of Internal Medicine, Tianjin Dongli Hospital, Tianjin 300300, China
| | - Fei Tang
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin 300170, China
| | - Tao Wang
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin 300170, China
| | - Jun-Qing Yan
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin 300170, China
| | - Feng-Hui Li
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin 300170, China
| | - Fu-Shuang Ha
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin 300170, China
| | - Xu Zhang
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin 300170, China
| | - Li Jing
- Department of Medical Laboratory, The Third Central Hospital of Tianjin, Tianjin 300170, China
| | - Jing Liang
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin 300170, China
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Ma X, Huang T, Chen X, Li Q, Liao M, Fu L, Huang J, Yuan K, Wang Z, Zeng Y. Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics. Signal Transduct Target Ther 2025; 10:63. [PMID: 39920130 PMCID: PMC11806117 DOI: 10.1038/s41392-024-02104-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 09/02/2024] [Accepted: 12/12/2024] [Indexed: 02/09/2025] Open
Abstract
Liver repair and regeneration are crucial physiological responses to hepatic injury and are orchestrated through intricate cellular and molecular networks. This review systematically delineates advancements in the field, emphasizing the essential roles played by diverse liver cell types. Their coordinated actions, supported by complex crosstalk within the liver microenvironment, are pivotal to enhancing regenerative outcomes. Recent molecular investigations have elucidated key signaling pathways involved in liver injury and regeneration. Viewed through the lens of metabolic reprogramming, these pathways highlight how shifts in glucose, lipid, and amino acid metabolism support the cellular functions essential for liver repair and regeneration. An analysis of regenerative variability across pathological states reveals how disease conditions influence these dynamics, guiding the development of novel therapeutic strategies and advanced techniques to enhance liver repair and regeneration. Bridging laboratory findings with practical applications, recent clinical trials highlight the potential of optimizing liver regeneration strategies. These trials offer valuable insights into the effectiveness of novel therapies and underscore significant progress in translational research. In conclusion, this review intricately links molecular insights to therapeutic frontiers, systematically charting the trajectory from fundamental physiological mechanisms to innovative clinical applications in liver repair and regeneration.
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Affiliation(s)
- Xiao Ma
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Tengda Huang
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Xiangzheng Chen
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Qian Li
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Mingheng Liao
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Li Fu
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Jiwei Huang
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Kefei Yuan
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Zhen Wang
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
| | - Yong Zeng
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
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Zott T, Pereyra D, Kersten I, Ortner M, Hüpper MN, Starlinger P, Berlakovich GA, Silberhumer GR. Characterization of Perioperative Serotonin in Patients Undergoing Orthotopic Liver Transplantation. J Clin Med 2024; 13:2640. [PMID: 38731169 PMCID: PMC11084934 DOI: 10.3390/jcm13092640] [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: 03/12/2024] [Revised: 04/13/2024] [Accepted: 04/27/2024] [Indexed: 05/13/2024] Open
Abstract
Background: Platelets were shown to be relevant for liver regeneration. In particular, platelet-stored serotonin (5-HT) proved to be a pro-regenerative factor in this process. The present study aimed to investigate the perioperative course of 5-HT and evaluate associations with patient and graft outcomes after othotopic liver transplantation (OLT). Methods: 5-HT was quantified in plasma and serum of 44 OLT recipients perioperatively, and in their respective donors. Olthoff's criteria for early allograft dysfunction (EAD) were used to evaluate postoperative outcomes. Results: Patients with higher donor intra-platelet 5-HT per platelet (IP 5-HT PP) values had significantly lower postoperative transaminases (ASAT POD1: p = 0.006, ASAT POD5: p = 0.006, ASAT POD10: p = 0.02, ALAT POD1: p = 0.034, ALAT POD5: p = 0.017, ALAT POD10: p = 0.04). No significant differences were seen between postoperative 5-HT values and the occurrence of EAD. A tendency was measured that donor IP 5-HT PP is lower in donor-recipient pairs that developed EAD (p = 0.07). Conclusions: Donor IP 5-HT PP might be linked to the postoperative development of EAD after OLT, as higher donor levels are correlated with a more favorable postoperative course of transaminases. Further studies with larger cohorts are needed to validate these findings.
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Affiliation(s)
- Tobias Zott
- Clinical Department of Transplantation, University Clinic for General Surgery, Medical University of Vienna, 1090 Vienna, Austria (G.R.S.)
- Clinical Department of General Surgery, University Clinic for General Surgery, Medical University of Vienna, 1090 Vienna, Austria
| | - David Pereyra
- Clinical Department of Transplantation, University Clinic for General Surgery, Medical University of Vienna, 1090 Vienna, Austria (G.R.S.)
- Clinical Department of General Surgery, University Clinic for General Surgery, Medical University of Vienna, 1090 Vienna, Austria
| | - Isabelle Kersten
- Clinical Department of Transplantation, University Clinic for General Surgery, Medical University of Vienna, 1090 Vienna, Austria (G.R.S.)
- Department of General Surgery, LMU Munich, 81377 Munich, Germany
| | - Max Ortner
- Clinical Department of Transplantation, University Clinic for General Surgery, Medical University of Vienna, 1090 Vienna, Austria (G.R.S.)
| | - Maria Noelle Hüpper
- Clinical Department of Transplantation, University Clinic for General Surgery, Medical University of Vienna, 1090 Vienna, Austria (G.R.S.)
| | - Patrick Starlinger
- Clinical Department of General Surgery, University Clinic for General Surgery, Medical University of Vienna, 1090 Vienna, Austria
- Department of General Surgery, Mayo Clinic, Rochester, MN 55902, USA
| | - Gabriela A. Berlakovich
- Clinical Department of Transplantation, University Clinic for General Surgery, Medical University of Vienna, 1090 Vienna, Austria (G.R.S.)
| | - Gerd R. Silberhumer
- Clinical Department of Transplantation, University Clinic for General Surgery, Medical University of Vienna, 1090 Vienna, Austria (G.R.S.)
- Clinical Department of General Surgery, University Clinic for General Surgery, Medical University of Vienna, 1090 Vienna, Austria
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Tietze L, Christ M, Yu J, Stock P, Nickel S, Schulze A, Bartels M, Tautenhahn HM, Christ B. Approaching Thrombospondin-1 as a Potential Target for Mesenchymal Stromal Cells to Support Liver Regeneration after Partial Hepatectomy in Mouse and Humans. Cells 2024; 13:529. [PMID: 38534373 PMCID: PMC10969617 DOI: 10.3390/cells13060529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 03/07/2024] [Accepted: 03/14/2024] [Indexed: 03/28/2024] Open
Abstract
Extended liver resection carries the risk of post-surgery liver failure involving thrombospondin-1-mediated aggravation of hepatic epithelial plasticity and function. Mesenchymal stromal cells (MSCs), by interfering with thrombospondin-1 (THBS1), counteract hepatic dysfunction, though the mechanisms involved remain unknown. Herein, two-thirds partial hepatectomy in mice increased hepatic THBS1, downstream transforming growth factor-β3, and perturbation of liver tissue homeostasis. All these events were ameliorated by hepatic transfusion of human bone marrow-derived MSCs. Treatment attenuated platelet and macrophage recruitment to the liver, both major sources of THBS1. By mitigating THBS1, MSCs muted surgery-induced tissue deterioration and dysfunction, and thus supported post-hepatectomy regeneration. After liver surgery, patients displayed increased tissue THBS1, which is associated with functional impairment and may indicate a higher risk of post-surgery complications. Since liver dysfunction involving THBS1 improves with MSC treatment in various animal models, it seems feasible to also modulate THBS1 in humans to impede post-surgery acute liver failure.
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Affiliation(s)
- Lysann Tietze
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany; (L.T.); (M.C.); (P.S.); (S.N.)
| | - Madlen Christ
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany; (L.T.); (M.C.); (P.S.); (S.N.)
| | - Jiyeon Yu
- Klinik für Allgemein-, Viszeral- und Thoraxchirurgie, Helios Park-Klinikum Leipzig, 04289 Leipzig, Germany; (J.Y.); (M.B.)
| | - Peggy Stock
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany; (L.T.); (M.C.); (P.S.); (S.N.)
| | - Sandra Nickel
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany; (L.T.); (M.C.); (P.S.); (S.N.)
| | - Annelie Schulze
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany; (L.T.); (M.C.); (P.S.); (S.N.)
| | - Michael Bartels
- Klinik für Allgemein-, Viszeral- und Thoraxchirurgie, Helios Park-Klinikum Leipzig, 04289 Leipzig, Germany; (J.Y.); (M.B.)
| | - Hans-Michael Tautenhahn
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany; (L.T.); (M.C.); (P.S.); (S.N.)
- Division of General, Visceral and Vascular Surgery, Jena University Hospital, 07747 Jena, Germany
- Research Programme “Else Kröner-Forschungskolleg AntiAge”, Jena University Hospital, 07747 Jena, Germany
| | - Bruno Christ
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany; (L.T.); (M.C.); (P.S.); (S.N.)
- Division of General, Visceral and Vascular Surgery, Jena University Hospital, 07747 Jena, Germany
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Lee FT, Williams J, Nordgren R, Schwarz JL, Setia N, Roggin K, Polite B, Rangrass G, Liao CY, Millis JM, Keutgen XM. Single center outcomes from parenchymal-sparing resections and microwave ablations for neuroendocrine tumor liver metastases. Am J Surg 2024; 229:17-23. [PMID: 37802701 DOI: 10.1016/j.amjsurg.2023.09.020] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 08/02/2023] [Accepted: 09/13/2023] [Indexed: 10/08/2023]
Abstract
BACKGROUND Reported outcomes after surgical debulking in patients with advanced neuroendocrine tumor liver metastases (NETLM) are sparse. METHODS NETLM patients that underwent surgical debulking from 2019 to 2021 were reviewed. Trends in perioperative liver function, complications, symptom response, and progression-free survival were examined. RESULTS 1069 liver lesions were debulked from 53 patients using a combination of parenchymal-sparing resections (PSR) and ultrasound-guided microwave ablations (MWA). Post-operative transaminitis and thrombocytopenia were common, and severity correlated with increasing number of lesions. Laboratory markers for synthetic liver function did not differ according to the number of lesions debulked. 13% of patients sustained a Clavien-Dindo grade 3 or 4 complication which was not associated with the number of lesions targeted. All patients with preoperative symptoms had improvement after surgery. Median time to progression was 10.9 months. CONCLUSIONS PSR with MWA for large numbers of NETLM is safe and effective for symptom control and does not affect synthetic liver function.
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Affiliation(s)
- Frances T Lee
- Southern Illinois University, Department of Surgery. 701 N. 1st St, Springfield IL 62794, USA
| | - Jelani Williams
- University of Chicago, Department of Surgery. 5841 S Maryland Ave, Chicago IL 60637, USA
| | - Rachel Nordgren
- University of Chicago, Department of Public Health Sciences. 5481 S Maryland Ave, Chicago, IL 60637, USA
| | - Jason L Schwarz
- University of Chicago, Department of Surgery. 5841 S Maryland Ave, Chicago IL 60637, USA
| | - Namrata Setia
- University of Chicago, Department of Pathology. 5841 S Maryland Ave, Chicago IL 60637, USA
| | - Kevin Roggin
- University of Chicago, Department of Surgery. 5841 S Maryland Ave, Chicago IL 60637, USA
| | - Blase Polite
- University of Chicago, Department of Medicine, Section of Hematology/Oncology. 5841 S Maryland Ave, Chicago IL 60637, USA
| | - Govind Rangrass
- University of Chicago, Department of Anesthesia and Critical Care. 5841 S Maryland Ave, Chicago IL 60637, USA
| | - Chih-Yi Liao
- University of Chicago, Department of Medicine, Section of Hematology/Oncology. 5841 S Maryland Ave, Chicago IL 60637, USA
| | - J Michael Millis
- University of Chicago, Department of Surgery. 5841 S Maryland Ave, Chicago IL 60637, USA
| | - Xavier M Keutgen
- University of Chicago, Department of Surgery. 5841 S Maryland Ave, Chicago IL 60637, USA.
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Cai W, Lin X, Guo Y, Lin X, Chen C. A nomogram for predicting prognosis in patients with transjugular intrahepatic portosystemic shunt creation based on deep learning-derived spleen volume-to-platelet ratio. Br J Radiol 2024; 97:600-606. [PMID: 38288507 DOI: 10.1093/bjr/tqad064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 11/09/2023] [Accepted: 12/21/2023] [Indexed: 03/01/2024] Open
Abstract
OBJECTIVES The objective of our study was to develop a nomogram to predict post-transjugular intrahepatic portosystemic shunt (TIPS) survival in patients with cirrhosis based on CT images. METHODS This retrospective cohort study included patients who had received TIPS operation at the Wenzhou Medical University First Affiliated Hospital between November 2013 and April 2017. To predict prognosis, a nomogram and Web-based probability were developed to assess the overall survival (OS) rates at 1, 3, and 5 years based on multivariate analyses. With deep learning algorithm, the automated measurement of liver and spleen volumes can be realized. We assessed the predictive accuracy and discriminative ability of the nomogram using the concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). RESULTS Age, total bilirubin, and spleen volume-to-platelet ratio (SVPR) were identified as the independent risk factors for OS. The nomogram was constructed based on the above risk factors. The C-index (0.80, 0.74, 0.70), ROC curve (area under curve: 0.828, 0.761, 0.729), calibration curve, and DCA showed that nomogram good at predictive value, stability, and clinical benefit in the prediction of 1-, 3-, 5-year OS in patients with TIPS creation. CONCLUSIONS We constructed a nomogram for predicting prognosis in patients with TIPS creation based on risk factors. The nomogram can help clinicians in identifying patients with poor prognosis, eventually facilitating earlier treatment and selecting suitable patients before TIPS. ADVANCES IN KNOWLEDGE This study developed the first nomogram based on SVPR to predict the prognosis of patients treated with TIPS. The nomogram could help clinician in non-invasive decision-making.
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Affiliation(s)
- Weimin Cai
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Xinran Lin
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Yu Guo
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Xiuqing Lin
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Chao Chen
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
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8
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Wen Y. The Role of Immune Cells in Liver Regeneration. LIVERS 2023; 3:383-396. [DOI: 10.3390/livers3030029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2025] Open
Abstract
The liver is the only organ that can regenerate and regain its original tissue-to-body weight ratio within a short period of time after tissue loss. Insufficient liver regeneration in patients after partial hepatectomy or liver transplantation with partial liver grafts often leads to post-hepatectomy liver failure or small-for-size syndrome, respectively. Enhancing liver regeneration after liver injury might improve outcomes and increase patient survival. Liver regeneration comprises hepatocyte proliferation, and hepatic progenitor cell expansion and differentiation into hepatocytes. The immune system is intensively involved in liver regeneration. The current review provides a comprehensive overview of the diverse roles played by immune cells in liver regeneration. Macrophages, neutrophils, eosinophils, basophils, mast cells, platelets, dendritic cells, type 1 innate lymphoid cells, B cells, and T cells are implicated in promoting liver regeneration, while natural killer cells and overactivated natural killer T cells are supposed to inhibit hepatocyte proliferation. We also highlight the predominant underlying mechanisms mediated by immune cells, which may contribute to the development of novel strategies for promoting liver regeneration in patients with liver diseases.
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Affiliation(s)
- Yankai Wen
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
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Starlinger P, Brunnthaler L, Watkins R, Pereyra D, Stift J, Finsterbusch M, Santol J, Gruenberger T, Assinger A, Smoot R. Tyrosine phosphorylation of YAP-1 in biliary epithelial cells mediates posthepatectomy liver regeneration and is affected by serotonin. J Cell Biochem 2023; 124:687-700. [PMID: 36946436 PMCID: PMC10200759 DOI: 10.1002/jcb.30398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 02/26/2023] [Accepted: 03/01/2023] [Indexed: 03/23/2023]
Abstract
Experimental data suggested activation of yes-associated protein (YAP-1) as a critical regulator of liver regeneration (LR). Serotonin (5-HT) promotes LR in rodent models and has been proposed to act via YAP-1. How 5-HT affects LR is incompletely understood. A possible mechanism how 5-HT affects human LR was explored. Sixty-one patients were included. Tissue samples prior and 2 h after induction of LR were collected. Circulating levels of 5-HT and osteopontin (OPN) were assessed. YAP-1, its phosphorylation states, cytokeratin 19 (CK-19) and OPN were assessed using immunofluorescence. A mouse model of biliary epithelial cells (BECs) specific deletion of YAP/TAZ was developed. YAP-1 increased as early as 2 h after induction of LR (p = 0.025) predominantly in BECs. BEC specific deletion of YAP/TAZ reduced LR after 70% partial hepatectomy in mice (Ki67%, p < 0.001). SSRI treatment, depleting intra-platelet 5-HT, abolished YAP-1 and OPN induction upon LR. Portal vein 5-HT levels correlated with intrahepatic YAP-1 expression upon LR (R = 0.703, p = 0.035). OPN colocalized with YAP-1 in BECs and its circulating levels increased in the liver vein 2 h after induction of LR (p = 0.017). In the context of LR tyrosine-phosphorylated YAP-1 significantly increased (p = 0.042). Stimulating BECs with 5-HT resulted in increased YAP-1 activation via tyrosine-phosphorylation and subsequently increased OPN expression. BECs YAP-1 appears to be critical for LR in mice and humans. Our evidence suggests that 5-HT, at least in part, exerts its pro-regenerative effects via YAP-1 tyrosine-phosphorylation in BECs and subsequent OPN-dependent paracrine immunomodulation.
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Affiliation(s)
- Patrick Starlinger
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN, USA
- Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria
| | - Laura Brunnthaler
- Center of Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria
| | - Ryan Watkins
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN, USA
| | - David Pereyra
- Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria
| | - Judith Stift
- Clinical Institute of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria
| | - Michaela Finsterbusch
- Center of Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria
| | - Jonas Santol
- Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria
| | - Thomas Gruenberger
- Department of Surgery, HPB Center, Viennese Health Network, Clinic Favoriten and Sigmund Freud Private University, Vienna, Austria
| | - Alice Assinger
- Center of Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria
| | - Rory Smoot
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN, USA
- Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA
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Tian H, Jiang X, Duan G, Chen J, Liu Q, Zhang Y, Li S, Bao X, Huang H. Preoperative inflammatory markers predict postoperative clinical outcomes in patients undergoing heart valve surgery: A large-sample retrospective study. Front Immunol 2023; 14:1159089. [PMID: 37063874 PMCID: PMC10102463 DOI: 10.3389/fimmu.2023.1159089] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Accepted: 03/20/2023] [Indexed: 04/03/2023] Open
Abstract
IntroductionPreoperative inflammation affects the postoperative outcomes of patients undergoing heart valve surgery. This study aimed to explore the role and predictive effects of preoperative inflammation on the primary outcomes after valvular cardiac surgery.MethodsThis retrospective study utilized a medical recording system to screen 5075 patients who underwent heart valve surgery. Data on the C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and neutrophil-to-lymphocyte ratio (NLR) before heart valve surgery were collected from the hospital’s medical system. Postoperative hepatic insufficiency, acute kidney injury, heart failure, and myocardial damage were assessed using blood indicators. Patients with and without prolonged mechanical ventilation, extended intensive care unit stays, prolonged hospital stays, and death within 30 days after surgery (considered the primary outcome in this study) were compared. Group comparisons, receiver operating characteristic (ROC) curve analyses, and logistic analyses were performed to determine the associations between preoperative inflammation and outcomes after heart valve surgery.ResultsA total of 3249 patients were included in the analysis. Significant differences in CRP level, ESR, and NLR were found between patients with and without postoperative adverse outcomes. ROC analysis showed that CRP levels >5 mg/L effectively predicted postoperative heart failure, and NLR >3.5 had a good predictive effect on all-cause mortality within 30 days after surgery. Patients with CRP levels >5 mg/L had a higher incidence of postoperative heart failure than other patients (20.7% vs. 12.6%, P<0.001), with a relative risk of 1.447 (95% confidence interval: 1.155–1.814). Patients with NLR >3.5 had a higher incidence of death within 30 days after surgery (5.3% vs. 1.2%, P<0.001), with a relative risk of 3.236 (95% confidence interval: 1.773–5.906).ConclusionPreoperative inflammation can affect postoperative outcomes in patients undergoing heart valve surgery. CRP level >5 mg/L and NLR >3.5 can effectively predict postoperative heart failure and death within 30 days after surgery, respectively.
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Affiliation(s)
- Hongni Tian
- Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Xuetao Jiang
- Department of Anesthesiology, Second Affiliated Hospital of Army Military Medical University, Chongqing, China
| | - Guangyou Duan
- Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Jie Chen
- Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Qi Liu
- Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Yamei Zhang
- Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Shiqi Li
- Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Xiaohang Bao
- Department of Anesthesiology, Second Affiliated Hospital of Army Military Medical University, Chongqing, China
- *Correspondence: Xiaohang Bao, ; He Huang,
| | - He Huang
- Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
- *Correspondence: Xiaohang Bao, ; He Huang,
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11
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Meng XQ, Miao H, Xia Y, Shen H, Qian Y, YanChen, Shen F, Guo J. A nomogram for predicting post-hepatectomy liver failure in patients with hepatocellular carcinoma based on spleen-volume-to-platelet ratio. Asian J Surg 2023; 46:399-404. [PMID: 35599113 DOI: 10.1016/j.asjsur.2022.05.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 04/04/2022] [Accepted: 05/06/2022] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Post-hepatectomy liver failure (PHLF) is one of the most serious complications after hepatectomy in patients with hepatocellular carcinoma (HCC), and has an association with high morbidity and mortality. This study aimed to explore the risk factors of PHLF and to establish and validate a nomogram to predict PHLF. METHODS We retrospectively analyzed 971 HCC patients undergoing major liver resection at the Eastern Hepatobiliary Surgery Hospital between 2011 and 2016, and established a nomogram based on multivariate analyses for predicting PHLF. The predictive accuracy and discriminative ability of the nomogram were evaluated by concordance index (C-index) and calibration curve. The predictive ability of PHLF of this nomogram was compared with conventional models using receiver operating characteristic (ROC) curves. RESULTS The incidence of PHLF was 18.8%. Multivariate analysis identified age, BMI, preoperative ascites, preoperative prealbumin, spleen volume-to-platelet ratio, total bilirubin, and intraoperative blood loss as independent predictors of PHLF. The area under ROC curve (AUROC) of the predictive model was 0.668 and was higher than that of the albumin-bilirubin score (ALBI). The optimal cut-off value of the model was 124. CONCLUSIONS We constructed a nomogram for predicting PHLF based on risk factors. The nomogram can assist clinicians in identifying patients with high-risk PHLF, eventually facilitating earlier interventions and improving clinical outcomes.
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Affiliation(s)
- Xue-Qin Meng
- Department of Ultrasound, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Hui Miao
- Department of Medical Genetics, College of Basic Medical Science, Second Military Medical University, Shanghai, China
| | - Yong Xia
- Department of Hepatic Surgery IV, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Hao Shen
- Department of Hepatic Surgery IV, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Yi Qian
- Department of Ultrasound, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - YanChen
- Department of Ultrasound, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Feng Shen
- Department of Hepatic Surgery IV, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Jia Guo
- Department of Ultrasound, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China.
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12
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Lisman T. Bleeding and thrombosis in cirrhosis. CARDIO-HEPATOLOGY 2023:165-202. [DOI: 10.1016/b978-0-12-817394-7.00010-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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13
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Li YR, Chen JD, Huang J, Wu FX, Jin GZ. Post-hepatectomy liver failure prediction and prevention: Development of a nomogram containing postoperative anticoagulants as a risk factor. Ann Hepatol 2022; 27:100744. [PMID: 35964908 DOI: 10.1016/j.aohep.2022.100744] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 07/15/2022] [Accepted: 07/19/2022] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Posthepatectomy liver failure (PHLF) is a serious complication after hepatectomy, and its effective methods for preoperative prediction are lacking. Here, we aim to identify predictive factors and build a nomogram to evaluate patients' risk of developing PHLF. PATIENTS AND METHODS A retrospective review of a training cohort, including 199 patients who underwent hepatectomy at the Shanghai Eastern Hepatobiliary Surgery Hospital, was conducted. Independent risk variables for PHLF were identified using multivariate analysis of perioperative variables, and a nomogram was used to build a predictive model. To test the predictive power, a prospective study in which a validation cohort of 71 patients was evaluated using the nomogram. The prognostic value of this nomogram was evaluated by the C-index. RESULTS Independent risk variables for PHLF were identified from perioperative variables. In multivariate analysis of the training cohort, tumor number, Pringle maneuver, blood loss, preoperative platelet count, postoperative ascites and use of anticoagulant medications were determined to be key risk factors for the development of PHLF, and they were selected for inclusion in our nomogram. The nomogram showed a 0.911 C-index for the training cohort. In the validation cohort, the nomogram also showed good prognostic value for predicting PHLF. The validation cohort was used with similarly successful results to evaluate risk in two previously published study models with calculated C-indexes of 0.718 and 0.711. CONCLUSION Our study establishes for the first time a novel nomogram that can be used to identify patients at risk of developing PHLF.
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Affiliation(s)
- Yi-Ran Li
- Department of Intensive Care Medicine, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Jin-Dong Chen
- School of Basic medical sciences, The Second Military Medical University, Shanghai, China
| | - Jian Huang
- Department of Third Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Fei-Xiang Wu
- Department of Intensive Care Medicine, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Medical University, Shanghai, China.
| | - Guang-Zhi Jin
- Department of Anesthesiology, Tongren Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
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14
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Wu T, Sui GQ, Teng DK, Luo Q, Wang H, Lin YQ. Study on Changes in Immune Function After Microwave Ablation of Papillary Thyroid Microcarcinoma. Cancer Manag Res 2022; 14:2861-2868. [PMID: 36171864 PMCID: PMC9510695 DOI: 10.2147/cmar.s358649] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Accepted: 09/04/2022] [Indexed: 11/23/2022] Open
Abstract
Background In recent years, papillary thyroid microcarcinoma (PTMC) has been a main cause of the high incidence of thyroid carcinoma. No existing study has reported whether microwave ablation (MWA) affects patients' immunity. Therefore, this study explored the effects of MWA treatment on the immune functions of patients with PTMC. Methods This study included 50 patients diagnosed with PTMC who received MWA treatment under ultrasound guidance at the ultrasound department of our hospital from January 2019 to October 2020. Changes in immune function after MWA treatment in PTMC patients were detected by T lymphocyte subsets and cytokines secreted by T helper cells. Results At 1 day and 2 weeks after MWA treatment, the proportions of CD3+, CD4+ and CD4+/CD8+ T lymphocyte subsets and the levels of the cytokines interleukin (IL)-2 and interferon (IFN)-γ in the peripheral blood of the patients were significantly higher than those before MWA treatment (P<0.05). The levels of CD8+ T lymphocytes, tumour necrosis factor (TNF)-α, IL-4, IL-6, IL-10 and IL-17A were not significantly different from those before MWA treatment (P>0.05). One month after MWA treatment, the proportions of CD3+, CD4+, CD8+ and CD4+/CD8+ T lymphocytes and the levels of the cytokines IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α and IL-17A were not significantly different from those before MWA treatment (P>0.05). Conclusion The immune functions of patients with PTMC are temporarily enhanced after MWA treatment, which has important clinical significance for patients' anti-PTMC ability.
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Affiliation(s)
- Ting Wu
- Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130000, People's Republic of China
| | - Guo-Qing Sui
- Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130000, People's Republic of China
| | - Deng-Ke Teng
- Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130000, People's Republic of China
| | - Qiang Luo
- Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130000, People's Republic of China
| | - Hui Wang
- Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130000, People's Republic of China
| | - Yuan-Qiang Lin
- Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130000, People's Republic of China
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15
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Parwaiz I, Hakeem A, Nwogwugwu O, Prasad R, Hidalgo E, Lodge P, Toogood G, Pathak S. Does ALT Correlate with Survival After Liver Resection for Colorectal Liver Metastases? J Clin Exp Hepatol 2022; 12:1285-1292. [PMID: 36157153 PMCID: PMC9499836 DOI: 10.1016/j.jceh.2022.04.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 04/24/2022] [Indexed: 12/12/2022] Open
Abstract
Background The pringle manoeuvre is commonly used during hepatectomy, which may cause ischaemia-reperfusion injury and transient liver dysfunction. Post-operative liver transaminases are often used to assess ischaemia-reperfusion injury, although there is conflicting evidence on survival outcomes. The primary aim was to assess post-operative alanine aminotransferase (ALT) with survival outcomes. Secondary aims were to assess ALT level with the length of stay and overall complications. Methods Post-operative day 2 ALT levels of five times the upper limit of normal (i.e. 280 U/L) were considered as clinically significant transaminitis. Kaplan-Meier survival curves were studied using log-rank analysis to identify the predictors of overall survival (OS) and recurrence-free survival (RFS). Results Out of 752 patients who underwent hepatectomy, 527 (70.1%) patients had low ALT (<280 U/L) and 225 (29.9%) patients had high ALT on day 2 post-op. Post-operative ALT did not affect OS (P = 0.883) or RFS (P = 0.063). Factors associated with a worse OS and RFS on multivariate analysis were pre-operative chemotherapy, number of tumours and largest tumour size (>4 cm). A high post-operative ALT was not associated with the increased length of stay or more complications. Conclusions Post-operative ALT does not affect survival outcomes post-hepatectomy for colorectal liver metastases.
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Affiliation(s)
- Iram Parwaiz
- Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, UK
| | - Abdul Hakeem
- St James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK
| | - Obi Nwogwugwu
- Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, UK
| | - Raj Prasad
- St James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK
| | - Ernest Hidalgo
- St James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK
| | - Peter Lodge
- St James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK
| | - Giles Toogood
- St James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK
| | - Samir Pathak
- Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, UK
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16
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Funayama M, Koreki A, Mimura Y, Takata T, Ogino S, Kurose S, Shimizu Y, Kudo S. Restrictive type and infectious complications might predict nadir hematological values among individuals with anorexia nervosa during the refeeding period: a retrospective study. J Eat Disord 2022; 10:64. [PMID: 35513879 PMCID: PMC9074196 DOI: 10.1186/s40337-022-00586-x] [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: 01/28/2022] [Accepted: 05/01/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Although hematological abnormalities in patients with anorexia nervosa have been documented, the mechanisms involved have not been fully clarified, especially during the refeeding period when hematological values further decrease after admission prior to improving. Here we address potential mechanisms underlying the hematological abnormalities of inpatients with anorexia nervosa during the refeeding period. METHODS We recruited patients from 101 admissions corresponding to 55 individual patients with anorexia nervosa with severe malnutrition (body mass index, 13.4 ± 3.4) from the neuropsychiatry unit in Ashikaga Red Cross Hospital during the period from October 1999 to March 2018. We analyzed three hematological cell measures, i.e., hemoglobin, white cell count, and platelet count, to determine their levels at admission and their lowest levels during the refeeding period and calculated the percent decrease in those values from admission to the nadir levels. We analyzed each measure using a general mixed model with explanatory variables, including data upon admission and a treatment-related indicator, i.e., energy intake. RESULTS The initial hemoglobin value of 12.1 ± 2.7 g/dl decreased by 22.3% to 9.4 ± 2.5 g/dl; the initial white cell count was 5387 ± 3474/μl, which decreased by 33.6% to 3576 ± 1440/μl; the initial platelet count of 226 ± 101 × 103/μl decreased by 24.3% to 171 ± 80 × 103/μl. All nadir levels were observed during the refeeding period from the fifth to tenth day of hospitalization. Significant correlations among the three hematological cell measures, particularly at the nadir levels, were found. Of note, 41.7% of our patients who received red blood cell transfusion during hospitalization showed normal hemoglobin levels upon admission. The anorexia nervosa restrictive type was associated with a lower nadir level of white blood cell count. Infectious complications were related to a lower nadir level of hemoglobin and a greater percent decrease in hemoglobin level as well as to the need for red blood cell transfusion. CONCLUSIONS Nadir hematological cell measures of inpatients with anorexia nervosa might be predicted by the restrictive type and infectious complications. The anorexia nervosa restrictive type was associated with further decrease in hematological values during the refeeding period.
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Affiliation(s)
- Michitaka Funayama
- Department of Neuropsychiatry, Ashikaga Red Cross Hospital, 284-1 Yobe, Ashikaga, Tochigi, 326-0843, Japan.
| | - Akihiro Koreki
- Department of Neuropsychiatry, Ashikaga Red Cross Hospital, 284-1 Yobe, Ashikaga, Tochigi, 326-0843, Japan.,Department of Neuropsychiatry, Keio University School of Medicine, Shinjuku, Tokyo, Japan.,Department of Psychiatry, National Hospital Organization Shimofusa Psychiatric Medical Center, Chiba, Japan
| | - Yu Mimura
- Department of Neuropsychiatry, Ashikaga Red Cross Hospital, 284-1 Yobe, Ashikaga, Tochigi, 326-0843, Japan.,Department of Neuropsychiatry, Keio University School of Medicine, Shinjuku, Tokyo, Japan
| | - Taketo Takata
- Department of Neuropsychiatry, Ashikaga Red Cross Hospital, 284-1 Yobe, Ashikaga, Tochigi, 326-0843, Japan
| | - Satoyuki Ogino
- Department of Neuropsychiatry, Ashikaga Red Cross Hospital, 284-1 Yobe, Ashikaga, Tochigi, 326-0843, Japan.,Department of Trauma and Critical Care Medicine, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
| | - Shin Kurose
- Department of Neuropsychiatry, Ashikaga Red Cross Hospital, 284-1 Yobe, Ashikaga, Tochigi, 326-0843, Japan.,Department of Neuropsychiatry, Keio University School of Medicine, Shinjuku, Tokyo, Japan.,Department of Psychiatry, National Hospital Organization Shimofusa Psychiatric Medical Center, Chiba, Japan
| | - Yusuke Shimizu
- Department of Neuropsychiatry, Ashikaga Red Cross Hospital, 284-1 Yobe, Ashikaga, Tochigi, 326-0843, Japan.,Department of Trauma and Critical Care Medicine, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
| | - Shun Kudo
- Department of Neuropsychiatry, Ashikaga Red Cross Hospital, 284-1 Yobe, Ashikaga, Tochigi, 326-0843, Japan.,Department of Neuropsychiatry, Keio University School of Medicine, Shinjuku, Tokyo, Japan
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17
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Liang C, Takahashi K, Furuya K, Ohkohchi N, Oda T. Dualistic role of platelets in living donor liver transplantation: Are they harmful? World J Gastroenterol 2022; 28:897-908. [PMID: 35317052 PMCID: PMC8908284 DOI: 10.3748/wjg.v28.i9.897] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 07/04/2021] [Accepted: 01/27/2022] [Indexed: 02/06/2023] Open
Abstract
Platelets are anucleate fragments mainly involved in hemostasis and thrombosis, and there is emerging evidence that platelets have other nonhemostatic potentials in inflammation, angiogenesis, regeneration and ischemia/reperfusion injury (I/R injury), which are involved in the physiological and pathological processes during living donor liver transplantation (LDLT). LDLT is sometimes associated with impaired regeneration and severe I/R injury, leading to postoperative complications and decreased patient survival. Recent studies have suggested that perioperative thrombocytopenia is associated with poor graft regeneration and postoperative morbidity in the short and long term after LDLT. Although it is not fully understood whether thrombocytopenia is the cause or result, increasing platelet counts are frequently suggested to improve posttransplant outcomes in clinical studies. Based on rodent experiments, previous studies have identified that platelets stimulate liver regeneration after partial hepatectomy. However, the role of platelets in LDLT is controversial, as platelets are supposed to aggravate I/R injury in the liver. Recently, a rat model of partial liver transplantation (LT) was used to demonstrate that thrombopoietin-induced thrombocytosis prior to surgery accelerated graft regeneration and improved the survival rate after transplantation. It was clarified that platelet-derived liver regeneration outweighed the associated risk of I/R injury after partial LT. Clinical strategies to increase perioperative platelet counts, such as thrombopoietin, thrombopoietin receptor agonist and platelet transfusion, may improve graft regeneration and survival after LDLT.
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Affiliation(s)
- Chen Liang
- Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
| | - Kazuhiro Takahashi
- Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
| | - Kinji Furuya
- Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
| | - Nobuhiro Ohkohchi
- Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
| | - Tatsuya Oda
- Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
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Kisaoglu A, Doğru V, Yilmaz VT, Demiryilmaz I, Avanaz A, Sarikaya SM, Dinc B, Aydinli B. Safety and Threshold Analysis of Preoperative Platelets in Right Lobe Living Donors for Liver Transplantation. J Gastrointest Surg 2022; 26:77-85. [PMID: 34100245 DOI: 10.1007/s11605-021-05047-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Accepted: 05/17/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND Low perioperative platelet count is a powerful independent risk factor for posthepatectomy liver failure. Usually, categorical effect of thrombocytopenia was taken into account; upper thresholds were not studied in depth, exclusively in living liver donors. METHODS Living liver donors who underwent right hepatectomy were included. Preoperative characteristics of donors were identified and examined to predict posthepatectomy liver failure. To eliminate selection bias, one-to-one propensity score matching was performed. RESULTS There were a total of 139 living donors and 40 (29%) donors developed posthepatectomy liver failure in the aftermath of the operation. Remnant liver volume ratio and preoperative platelet count were identified as adjustable independent risk factors (OR: 0.89 and 0.99, 95% CI: 0.79-0.99 and 0.98-0.99, respectively). After propensity score matching, odds ratio of preoperative platelet count was 0.99 (95% CI: 0.98-1.00). CONCLUSIONS Preoperative platelet count, in addition to remnant liver volume ratio, can be used as a surrogate marker to predict the risk of posthepatectomy liver failure in living liver right lobe donors. Probability curves figured out from logistic regression analysis, in this regard, provided an explicit perspective of platelets having a decisive role on liver donor safety. Thus, remaining in safer remnant liver volume ratio limits with respect to preoperative platelet count should be addressed in safe donor selection strategies.
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Affiliation(s)
- Abdullah Kisaoglu
- Department of Organ Transplantation, Akdeniz University School of Medicine, Antalya, Turkey
| | - Volkan Doğru
- Department of General Surgery, Akdeniz University School of Medicine, Antalya, Turkey.
| | - Vural Taner Yilmaz
- Department of Organ Transplantation, Akdeniz University School of Medicine, Antalya, Turkey
| | - Ismail Demiryilmaz
- Department of Organ Transplantation, Akdeniz University School of Medicine, Antalya, Turkey
| | - Ali Avanaz
- Department of Organ Transplantation, Akdeniz University School of Medicine, Antalya, Turkey
| | | | - Bora Dinc
- Department of Anesthesiology, Akdeniz University School of Medicine, Antalya, Turkey
| | - Bulent Aydinli
- Department of Organ Transplantation, Akdeniz University School of Medicine, Antalya, Turkey
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Biondo-Simões MDELP, Pessini VCDEA, Ichi CA, Robes RR, Ioshii S. Acetylsalicylic acid (Aspirin®) and liver regeneration: experimental study in rats. Rev Col Bras Cir 2021; 48:e20213164. [PMID: 34816883 PMCID: PMC10683428 DOI: 10.1590/0100-6991e-20213164] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 10/06/2021] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVE to evaluate the influence of acetylsalicylic acid (ASA) on cell proliferation after partial hepatectomy in rats. METHODS 40 male Wistar rats were separated into four groups of ten rats each. Groups 1 and 2 (controls): undergoing 30% partial hepatectomy and, after one day (group 1) and seven days (group 2), to euthanasia; daily administration of 0.9% saline solution (1mL per 200g of body weight). Groups 3 and 4 (experimental): undergoing 30% partial hepatectomy and, after one day (group 3) and seven days (group 4), to euthanasia; daily administration of ASA (40mg/mL, 1mL per 200g of body weight). The absolute number of cells stained with PCNA was counted in photomicrographs, in five fields, and it was calculated the mean of positive cells per animal and per group. RESULTS the final mean of PCNA+ cells per group was: in group 1, 17.57 ± 6.77; in group 2, 19.31 ± 5.30; in group 3, 27.46 ± 11.55; and, in group 4, 12.40 ± 5.23. There was no significant difference at the two evaluation times in the control group (p=0.491), but there was in the experimental group (p=0.020), with a lower number of PCNA+ cells on the seventh day. The comparison between the two groups, on the first day, showed more PCNA+ cells in the livers of the animals that received ASA (p=0.047), and on the seventh day the number was lower in the experimental group (p=0.007). CONCLUSION ASA induced greater hepatocyte proliferation.
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Affiliation(s)
| | | | | | - Rogério Ribeiro Robes
- - Universidade Federal do Paraná (UFPR), Departamento de Veterinária - Curitiba - PR - Brasil
| | - Sérgio Ioshii
- - Universidade Federal do Paraná (UFPR), Departamento de Anatomia Patológica - Curitiba - PR - Brasil
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20
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Jiang H, Li Y, Sheng Q, Dou X. Relationship between Hepatitis B virus infection and platelet production and dysfunction. Platelets 2021; 33:212-218. [PMID: 34806523 DOI: 10.1080/09537104.2021.2002836] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Hepatitis B virus (HBV) is a kind of hepatotropic DNA virus. The main target organ is liver, except for liver, HBV has been found in a variety of extrahepatic tissues, such as kidney, thyroid, pancreas, bone marrow, etc. HBV can cause severe complications by invading these tissues. Among them, pancytopenia is one of the common complications, especially thrombocytopenia that causes life-threatening bleeding. However, the mechanism of thrombocytopenia is unclear and the treatment is extremely difficult. It has been confirmed that HBV has a close relationship with platelets. HBV can directly infect bone marrow, inhibit platelet production, and accelerate platelet destruction by activating monocyte-macrophage system and immune system. While platelets act as a double-edged sword to HBV. On one hand, the activated platelets can degranulate and release inflammatory mediators to help clear the viruses. Furthermore, platelets can provide anti-fibrotic molecules to improve liver functions and reduce hepatic fibrosis. On the other hand, platelets can also cause negative effects. The infected platelets collect HBV-specific CD8+ T cells and nonspecific inflammatory cells into liver parenchyma, inducing chronic inflammation, liver fibrosis and hepatic carcinoma. This article explores the interaction between HBV infection and platelets, providing a theoretical basis for clinical treatment of thrombocytopenia and severe hemorrhage caused by HBV infection.
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Affiliation(s)
- Huinan Jiang
- Department of Infectious Diseases, China Medical University of Shengjing Hospital, Shenyang, China.,Liaoning Key Laboratory of Viral Hepatitis, China Medical University of Shengjing Hospital, Shenyang, China
| | - Yanwei Li
- Department of Infectious Diseases, China Medical University of Shengjing Hospital, Shenyang, China.,Liaoning Key Laboratory of Viral Hepatitis, China Medical University of Shengjing Hospital, Shenyang, China
| | - Qiuju Sheng
- Department of Infectious Diseases, China Medical University of Shengjing Hospital, Shenyang, China.,Liaoning Key Laboratory of Viral Hepatitis, China Medical University of Shengjing Hospital, Shenyang, China
| | - Xiaoguang Dou
- Department of Infectious Diseases, China Medical University of Shengjing Hospital, Shenyang, China.,Liaoning Key Laboratory of Viral Hepatitis, China Medical University of Shengjing Hospital, Shenyang, China
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21
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Wang Q, Wang A, Sparrelid E, Zhang J, Zhao Y, Ma K, Brismar TB. Predictive value of gadoxetic acid-enhanced MRI for posthepatectomy liver failure: a systematic review. Eur Radiol 2021; 32:1792-1803. [PMID: 34562137 PMCID: PMC8831250 DOI: 10.1007/s00330-021-08297-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 07/21/2021] [Accepted: 08/23/2021] [Indexed: 12/04/2022]
Abstract
Objectives Effective and non-invasive biomarkers to predict and avoid posthepatectomy liver failure (PHLF) are urgently needed. This systematic review aims to evaluate the efficacy of gadoxetic acid–enhanced MRI-derived parameters as an imaging biomarker in preoperative prediction of PHLF. Methods A systematic literature search was performed in the databases of PubMed/Medline, Web of Science, Embase, and Cochrane Library up to 11 December 2020. Studies evaluating the incidence of PHLF on patients who underwent hepatectomy with preoperative liver function assessment using gadoxetic acid–enhanced MRI were included. Data was extracted using pre-designed tables. The Quality In Prognostic Studies (QUIPS) tool was adopted to evaluate the risk of bias. Results A total of 15 studies were identified for qualitative synthesis and most studies were marked as low to moderate risk of bias in each domain of QUIPS. The most commonly used parameter was relative liver enhancement or its related parameters. The reported incidence of PHLF ranged from 3.9 to 40%. The predictive sensitivity and specificity of gadoxetic acid–enhanced MRI parameters varied from 75 to 100% and from 54 to 93% in ten reported studies. A majority of the studies revealed that the gadoxetic acid–enhanced MRI parameter was a predictor for PHLF. Conclusions Gadoxetic acid–enhanced MRI showed a high predictive capacity for PHLF and represents a promising imaging biomarker in prediction of PHLF. Multicenter, prospective trials with large sample size and reliable, unified liver function parameters are required to validate the efficacy of individual liver function parameters. Key Points • There is an obvious heterogeneity of the published studies, not only in variance of MRI liver function parameters but also in indication and extent of the liver resection. • Signal intensity (SI)–based parameters derived from gadoxetic acid–enhanced MRI are the commonly used method for PHLF prediction. • Gadoxetic acid–enhanced MRI-derived parameters showed high predictive efficacy for PHLF and can potentially serve as a predictor for the incidence of PHLF. Supplementary Information The online version contains supplementary material available at 10.1007/s00330-021-08297-8.
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Affiliation(s)
- Qiang Wang
- Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
- Department of Radiology, Karolinska University Hospital Huddinge, 141 86, Stockholm, Sweden
| | - Anrong Wang
- Department of Hepatobiliary Surgery, People's Hospital of Dianjiang County, Chongqing, China
| | - Ernesto Sparrelid
- Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Jiaxing Zhang
- Department of Pharmacy, Guizhou Provincial People's Hospital, Guiyang, Guizhou Province, China
| | - Ying Zhao
- Experimental Cancer Medicine, Clinical Research Center, Karolinska Institutet, Stockholm, Sweden
- Clinical Research Center (KFC) and Center for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Kuansheng Ma
- Institute of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China
| | - Torkel B Brismar
- Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
- Department of Radiology, Karolinska University Hospital Huddinge, 141 86, Stockholm, Sweden.
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22
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Xu H, Li YM, Yi Y, Zheng YW, Ohkohchi N. The Effect of the Platelet Administration for the Patients with Liver Dysfunction after Liver Resection: Preliminary Clinical Trial. Case Rep Gastrointest Med 2021; 2021:9948854. [PMID: 34540297 PMCID: PMC8448609 DOI: 10.1155/2021/9948854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 09/02/2021] [Indexed: 11/17/2022] Open
Abstract
The aim of this study is to investigate the effect of platelet on the improvement of deteriorated liver function after liver resection. Six patients with hepatocellular carcinoma and liver cirrhosis have received the partial hepatectomy in the institution. Their Child-Pugh grade was B, and platelet count was below 7,000/µl. After hepatectomy, 20 units of platelet transfusion were carried out, liver function and side effects were investigated after 4 weeks, and the number of platelets increased to approximately 15,000/µl. Liver functions, such as aspartate transaminase (AST), alanine aminotransferase (ALT), cholinesterase (ChE), and prothrombin time, as well as albumin, recover to the same level as those before operation and 4 weeks after the operation. Any side effects were not recognized in all patients. Administration of platelets for cirrhotic patient with hepatectomy was carried with safety. But remarkable effect on the improvement of liver function was not recognized.
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Affiliation(s)
- Hui Xu
- Institute of Regenerative Medicine and Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212001, Jiangsu, China
| | - Yu-Mei Li
- Institute of Regenerative Medicine and Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212001, Jiangsu, China
| | - Yongxiang Yi
- Department of Surgery, The Second Hospital of Nanjing, Nanjing 210003, China
| | - Yun-Wen Zheng
- Institute of Regenerative Medicine and Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212001, Jiangsu, China
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
- Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, and School of Biotechnology and Heath Sciences, Wuyi University, Jiangmen 529020, Guangdong Province, China
- Yokohama City University School of Medicine, Yokohama, Kanagawa 234-0006, Japan
| | - Nobuhiro Ohkohchi
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
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23
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Han S. Possible roles of platelets in liver transplantation: regeneration and cancer recurrence. Anesth Pain Med (Seoul) 2021; 16:225-231. [PMID: 34352964 PMCID: PMC8342825 DOI: 10.17085/apm.21063] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 07/03/2021] [Indexed: 12/28/2022] Open
Abstract
When tissue injury results in breakage, platelets are not only involved in plug formation and wound sealing, but they also play an important role throughout the tissue recovery process. Specifically, platelets accumulate at the site of injury and release a large number of biologically active mediators at injury sites, which initiate or modulate damaged tissue regeneration. Moreover, extensive experimental evidence has elucidated the involvement of platelets in tumor growth and metastasis. As such, this mini-review aimed to highlight the relatively lesser known functions of platelets.
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Affiliation(s)
- Sangbin Han
- Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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24
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Starlinger P, Pereyra D, Hackl H, Ortmayr G, Braunwarth E, Santol J, Najarnia S, Driedger MR, Gregory L, Alva‐Ruiz R, Glasgow A, Assinger A, Nagorney DM, Habermann EB, Staetttner S, Cleary SP, Smoot RL, Gruenberger T. Consequences of Perioperative Serotonin Reuptake Inhibitor Treatment During Hepatic Surgery. Hepatology 2021; 73:1956-1966. [PMID: 33078426 PMCID: PMC8251772 DOI: 10.1002/hep.31601] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 09/14/2020] [Accepted: 10/01/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Platelet-stored serotonin critically affects liver regeneration in mice and humans. Selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenalin reuptake inhibitors (SNRIs) reduce intraplatelet serotonin. As SSRIs/SNRIs are now one of the most commonly prescribed drugs in the United States and Europe and given serotonin's impact on liver regeneration, we evaluated whether perioperative use of SSRIs/SNRIs affects outcome after hepatic resection. APPROACH AND RESULTS Consecutive patients undergoing hepatic resection (n = 754) were retrospectively included from prospectively maintained databases from two European institutions. Further, an independent cohort of 495 patients from the United States was assessed to validate our exploratory findings. Perioperative intake of SSRIs/SNRIs was recorded, and patients were followed up for postoperative liver dysfunction (LD), morbidity, and mortality. Perioperative intraplatelet serotonin levels were significantly decreased in patients receiving SSRI/SNRI treatment. Patients treated with SSRIs/SNRIs showed a higher incidence of morbidity, severe morbidity, LD, and LD requiring intervention. Associations were confirmed in the independent validation cohort. Combined cohorts documented a significant increase in deleterious postoperative outcome (morbidity odds ratio [OR], 1.56; 95% confidence interval [CI], 1.07-2.31; severe morbidity OR, 1.86; 95% CI, 1.22-2.79; LD OR, 1.96; 95% CI, 1.23-3.06; LD requiring intervention OR, 2.22; 95% CI, 1.03-4.36). Further, multivariable analysis confirmed the independent association of SSRIs/SNRIs with postoperative LD, which was closely associated with postoperative 90-day mortality and 1-year overall survival. CONCLUSIONS We observed a significant association of perioperative SSRI/SNRI intake with adverse postoperative outcome after hepatic resection. This indicates that SSRIs/SNRIs should be avoided perioperatively in patients undergoing hepatic resections.
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Affiliation(s)
- Patrick Starlinger
- Department of SurgeryMedical University of ViennaGeneral HospitalViennaAustria
- Department of SurgeryDivision of Hepatobiliary and Pancreas SurgeryMayo ClinicRochesterMN
| | - David Pereyra
- Department of SurgeryMedical University of ViennaGeneral HospitalViennaAustria
| | - Hubert Hackl
- Institute of BioinformaticsBiocenterMedical University of InnsbruckInnsbruckAustria
| | - Gregor Ortmayr
- Department of SurgeryMedical University of ViennaGeneral HospitalViennaAustria
| | - Eva Braunwarth
- Department of Visceral, Transplantation and Thoracic SurgeryMedical University InnsbruckInnsbruckAustria
| | - Jonas Santol
- Department of SurgeryMedical University of ViennaGeneral HospitalViennaAustria
| | - Sina Najarnia
- Department of SurgeryMedical University of ViennaGeneral HospitalViennaAustria
| | - Michael R. Driedger
- Department of SurgeryDivision of Hepatobiliary and Pancreas SurgeryMayo ClinicRochesterMN
| | - Lindsey Gregory
- Department of SurgeryDivision of Hepatobiliary and Pancreas SurgeryMayo ClinicRochesterMN
| | - Roberto Alva‐Ruiz
- Department of SurgeryDivision of Hepatobiliary and Pancreas SurgeryMayo ClinicRochesterMN
| | - Amy Glasgow
- Robert D. and Patricia E. Kern Center for the Science of Health Care DeliverMayo ClinicRochesterMN
| | - Alice Assinger
- Center of Physiology and PharmacologyMedical University of ViennaViennaAustria
| | - David M. Nagorney
- Department of SurgeryDivision of Hepatobiliary and Pancreas SurgeryMayo ClinicRochesterMN
| | - Elizabeth B. Habermann
- Robert D. and Patricia E. Kern Center for the Science of Health Care DeliverMayo ClinicRochesterMN
| | - Stefan Staetttner
- Department of Visceral, Transplantation and Thoracic SurgeryMedical University InnsbruckInnsbruckAustria
- Department of General, Visceral and Vascular SurgerySKG KlinikumVöcklabruckAustria
| | - Sean P. Cleary
- Department of SurgeryDivision of Hepatobiliary and Pancreas SurgeryMayo ClinicRochesterMN
| | - Rory L. Smoot
- Department of SurgeryDivision of Hepatobiliary and Pancreas SurgeryMayo ClinicRochesterMN
| | - Thomas Gruenberger
- Department of SurgeryHPB CenterViennese Health NetworkClinic Favoriten and Sigmund Freud Private UniversityViennaAustria
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25
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Till Death Do Us Part-The Multifaceted Role of Platelets in Liver Diseases. Int J Mol Sci 2021; 22:ijms22063113. [PMID: 33803718 PMCID: PMC8003150 DOI: 10.3390/ijms22063113] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 03/09/2021] [Accepted: 03/16/2021] [Indexed: 02/07/2023] Open
Abstract
Platelets are tightly connected with the liver, as both their production and their clearance are mediated by the liver. Platelets, in return, participate in a variety of liver diseases, ranging from non-alcoholic fatty liver diseases, (viral) hepatitis, liver fibrosis and hepatocellular carcinoma to liver regeneration. Due to their versatile functions, which include (1) regulation of hemostasis, (2) fine-tuning of immune responses and (3) release of growth factors and cellular mediators, platelets quickly adapt to environmental changes and modulate disease development, leading to different layers of complexity. Depending on the (patho)physiological context, platelets exert both beneficial and detrimental functions. Understanding the precise mechanisms through which platelet function is regulated at different stages of liver diseases and how platelets interact with various resident and non-resident liver cells helps to draw a clear picture of platelet-related therapeutic interventions. Therefore, this review summarizes the current knowledge on platelets in acute and chronic liver diseases and aims to shed light on how the smallest cells in the circulatory system account for changes in the (patho)physiology of the second largest organ in the human body.
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26
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Ju BJ, Jin M, Tian Y, Zhen X, Kong DX, Wang WL, Yan S. Model for liver hardness using two-dimensional shear wave elastography, durometer, and preoperative biomarkers. World J Gastrointest Surg 2021; 13:127-140. [PMID: 33643533 PMCID: PMC7898182 DOI: 10.4240/wjgs.v13.i2.127] [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: 08/27/2020] [Revised: 11/27/2020] [Accepted: 12/17/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Post-hepatectomy liver failure (PHLF) increases morbidity and mortality after liver resection for patients with advanced liver fibrosis and cirrhosis. Preoperative liver stiffness using two-dimensional shear wave elastography (2D-SWE) is widely used to evaluate the degree of fibrosis. However, the 2D-SWE results were not accurate. A durometer measures hardness by quantifying the ability of a material to locally resist the intrusion of hard objects into its surface. However, the durometer score can only be obtained during surgery.
AIM To measure correlations among 2D-SWE, palpation by surgeons, and durometer-measured objective liver hardness and to construct a liver hardness regression model.
METHODS We enrolled 74 hepatectomy patients with liver hardness in a derivation cohort. Tactile-based liver hardness scores (0-100) were determined through palpation of the liver tissue by surgeons. Additionally, liver hardness was measured using a durometer. Correlation coefficients for durometer-measured hardness and preoperative parameters were calculated. Multiple linear regression models were constructed to select the best predictive durometer scale. Receiver operating characteristic (ROC) curves and univariate and multivariate analyses were used to calculate the best model’s prediction of PHLF and risk factors for PHLF, respectively. A separate validation cohort (n = 162) was used to evaluate the model.
RESULTS The stiffness measured using 2D-SWE and palpation scale had good linear correlation with durometer-measured hardness (Pearson rank correlation coefficient 0.704 and 0.729, respectively, P < 0.001). The best model for the durometer scale (hardness scale model) was based on stiffness, hepatitis B virus surface antigen, and albumin level and had an R2 value of 0.580. The area under the ROC for the durometer and hardness scale for PHLF prediction were 0.807 (P = 0.002) and 0.785 (P = 0.005), respectively. The optimal cutoff value of the durometer and hardness scale was 27.38 (sensitivity = 0.900, specificity = 0.660) and 27.87 (sensitivity = 0.700, specificity = 0.787), respectively. Patients with a hardness scale score of > 27.87 were at a significantly higher risk of PHLF with hazard ratios of 7.835 (P = 0.015). The model’s PHLF predictive ability was confirmed in the validation cohort.
CONCLUSION Liver stiffness assessed by 2D-SWE and palpation correlated well with durometer hardness values. The multiple linear regression model predicted durometer hardness values and PHLF.
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Affiliation(s)
- Bing-Jie Ju
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou 310009, Zhejiang Province, China
- Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou 310009, Zhejiang Province, China
- Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou 310009, Zhejiang Province, China
- Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310009, Zhejiang Province, China
| | - Ming Jin
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou 310009, Zhejiang Province, China
- Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou 310009, Zhejiang Province, China
- Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou 310009, Zhejiang Province, China
- Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310009, Zhejiang Province, China
| | - Yang Tian
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou 310009, Zhejiang Province, China
- Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou 310009, Zhejiang Province, China
- Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou 310009, Zhejiang Province, China
- Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310009, Zhejiang Province, China
| | - Xiang Zhen
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou 310009, Zhejiang Province, China
- Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou 310009, Zhejiang Province, China
- Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou 310009, Zhejiang Province, China
- Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310009, Zhejiang Province, China
| | - De-Xing Kong
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
- School of Mathematical Sciences, Zhejiang University, Hangzhou 310027, Zhejiang Province, China
| | - Wei-Lin Wang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou 310009, Zhejiang Province, China
- Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou 310009, Zhejiang Province, China
- Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou 310009, Zhejiang Province, China
- Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310009, Zhejiang Province, China
| | - Sheng Yan
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou 310009, Zhejiang Province, China
- Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou 310009, Zhejiang Province, China
- Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou 310009, Zhejiang Province, China
- Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310009, Zhejiang Province, China
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27
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Arisaka S, Matsuyama R, Goto K, Suwa Y, Mori R, Morioka D, Taguri M, Endo I. Predictive Ability of Preoperative PT-INR and Postoperative MCP1 for Post-hepatectomy Liver Failure. In Vivo 2021; 34:1255-1263. [PMID: 32354916 DOI: 10.21873/invivo.11899] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Revised: 03/09/2020] [Accepted: 03/12/2020] [Indexed: 01/13/2023]
Abstract
BACKGROUND We sought a diagnostic tool using perioperative variables that might predict post-hepatectomy liver failure (PHLF). PATIENTS AND METHODS In 68 patients undergoing major hepatectomy, data on inflammatory markers and coagulation factors were prospectively collected and were compared between patients with International Study Group of Liver Surgery definition grade B/C PHLF (LF group) and those without LF (non-LF group). RESULTS Preoperatively, the LF group (n=9; 13.2%) had a lower platelet count and a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) activity and a higher prothrombin time-International Normalized Ratio (PT-INR) than the non-LF group. On postoperative day 1, the LF group had significantly higher serum interleukin 6 (IL6), C-C motif chemokine ligand 2 (CCL2), and IL10 levels than the non-LF group. The logistic regression model that included preoperative PT-INR and CCL2 on postoperative day 1 predicted grade B/C PHLF with 100% sensitivity and 89.8% specificity. CONCLUSION Our findings suggest that the combination of preoperative PT-INR and CCL2 on postoperative day 1 can predict PHLF earlier and precisely after major hepatectomy.
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Affiliation(s)
- Sayaka Arisaka
- Department of Gastroenterological Surgery, Yokohama City University, Yokohama, Japan
| | - Ryusei Matsuyama
- Department of Gastroenterological Surgery, Yokohama City University, Yokohama, Japan
| | - Koki Goto
- Department of Gastroenterological Surgery, Yokohama City University, Yokohama, Japan
| | - Yusuke Suwa
- Department of Gastroenterological Surgery, Yokohama City University, Yokohama, Japan
| | - Ryutaro Mori
- Department of Gastroenterological Surgery, Yokohama City University, Yokohama, Japan
| | - Daisuke Morioka
- Department of Gastroenterological Surgery, Yokohama City University, Yokohama, Japan
| | - Masataka Taguri
- Department of Biostatistics, Yokohama City University, Yokohama, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University, Yokohama, Japan
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28
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Avolio AW, Franco A, Schlegel A, Lai Q, Meli S, Burra P, Patrono D, Ravaioli M, Bassi D, Ferla F, Pagano D, Violi P, Camagni S, Dondossola D, Montalti R, Alrawashdeh W, Vitale A, Teofili L, Spoletini G, Magistri P, Bongini M, Rossi M, Mazzaferro V, Di Benedetto F, Hammond J, Vivarelli M, Agnes S, Colledan M, Carraro A, Cescon M, De Carlis L, Caccamo L, Gruttadauria S, Muiesan P, Cillo U, Romagnoli R, De Simone P. Development and Validation of a Comprehensive Model to Estimate Early Allograft Failure Among Patients Requiring Early Liver Retransplant. JAMA Surg 2020; 155:e204095. [PMID: 33112390 PMCID: PMC7593884 DOI: 10.1001/jamasurg.2020.4095] [Citation(s) in RCA: 75] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 06/21/2020] [Indexed: 12/15/2022]
Abstract
IMPORTANCE Expansion of donor acceptance criteria for liver transplant increased the risk for early allograft failure (EAF), and although EAF prediction is pivotal to optimize transplant outcomes, there is no consensus on specific EAF indicators or timing to evaluate EAF. Recently, the Liver Graft Assessment Following Transplantation (L-GrAFT) algorithm, based on aspartate transaminase, bilirubin, platelet, and international normalized ratio kinetics, was developed from a single-center database gathered from 2002 to 2015. OBJECTIVE To develop and validate a simplified comprehensive model estimating at day 10 after liver transplant the EAF risk at day 90 (the Early Allograft Failure Simplified Estimation [EASE] score) and, secondarily, to identify early those patients with unsustainable EAF risk who are suitable for retransplant. DESIGN, SETTING, AND PARTICIPANTS This multicenter cohort study was designed to develop a score capturing a continuum from normal graft function to nonfunction after transplant. Both parenchymal and vascular factors, which provide an indication to list for retransplant, were included among the EAF determinants. The L-GrAFT kinetic approach was adopted and modified with fewer data entries and novel variables. The population included 1609 patients in Italy for the derivation set and 538 patients in the UK for the validation set; all were patients who underwent transplant in 2016 and 2017. MAIN OUTCOMES AND MEASURES Early allograft failure was defined as graft failure (codified by retransplant or death) for any reason within 90 days after transplant. RESULTS At day 90 after transplant, the incidence of EAF was 110 of 1609 patients (6.8%) in the derivation set and 41 of 538 patients (7.6%) in the external validation set. Median (interquartile range) ages were 57 (51-62) years in the derivation data set and 56 (49-62) years in the validation data set. The EASE score was developed through 17 entries derived from 8 variables, including the Model for End-stage Liver Disease score, blood transfusion, early thrombosis of hepatic vessels, and kinetic parameters of transaminases, platelet count, and bilirubin. Donor parameters (age, donation after cardiac death, and machine perfusion) were not associated with EAF risk. Results were adjusted for transplant center volume. In receiver operating characteristic curve analyses, the EASE score outperformed L-GrAFT, Model for Early Allograft Function, Early Allograft Dysfunction, Eurotransplant Donor Risk Index, donor age × Model for End-stage Liver Disease, and Donor Risk Index scores, estimating day 90 EAF in 87% (95% CI, 83%-91%) of cases in both the derivation data set and the internal validation data set. Patients could be stratified in 5 classes, with those in the highest class exhibiting unsustainable EAF risk. CONCLUSIONS AND RELEVANCE This study found that the developed EASE score reliably estimated EAF risk. Knowledge of contributing factors may help clinicians to mitigate risk factors and guide them through the challenging clinical decision to allocate patients to early liver retransplant. The EASE score may be used in translational research across transplant centers.
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Affiliation(s)
- Alfonso W. Avolio
- Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
- Università Cattolica del Sacro Cuore, Rome, Italy
| | - Antonio Franco
- Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
| | | | | | | | | | | | | | | | | | - Duilio Pagano
- ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy
| | | | | | - Daniele Dondossola
- Fondazione IRCCS Ospedale Maggiore Policlinico, Università degli Studi, Milan, Italy
| | | | | | | | - Luciana Teofili
- Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
- Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gabriele Spoletini
- Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
- Newcastle Upon Tyne Hospital, Newcastle Upon Tyne, United Kingdom
| | | | - Marco Bongini
- Istituto Nazionale Tumori, IRCCS, and Università degli Studi, Milan, Italy
| | | | | | | | - John Hammond
- Newcastle Upon Tyne Hospital, Newcastle Upon Tyne, United Kingdom
| | | | - Salvatore Agnes
- Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
- Università Cattolica del Sacro Cuore, Rome, Italy
| | | | | | - Matteo Cescon
- S. Orsola-Malpighi University Hospital, Bologna, Italy
| | | | - Lucio Caccamo
- Fondazione IRCCS Ospedale Maggiore Policlinico, Università degli Studi, Milan, Italy
| | - Salvatore Gruttadauria
- ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy
| | - Paolo Muiesan
- Queen Elizabeth Hospital, Birmingham, United Kingdom
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Issues to be considered to address the future liver remnant prior to major hepatectomy. Surg Today 2020; 51:472-484. [PMID: 32894345 DOI: 10.1007/s00595-020-02088-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 07/08/2020] [Indexed: 02/08/2023]
Abstract
An accurate preoperative evaluation of the hepatic function and application of portal vein embolization in selected patients have helped improve the safety of major hepatectomy. In planning major hepatectomy, however, several issues remain to be addressed. The first is which cut-off values for serum total bilirubin level and prothrombin time should be used to define post-hepatectomy liver failure. Other issues include what minimum future liver remnant (FLR) volume is required; whether the total liver volume measured using computed tomography or the standard liver volume calculated based on the body surface area should be used to assess the adequacy of the FLR volume; whether there is a discrepancy between the FLR volume and function during the recovery period after portal vein embolization or hepatectomy; and how best the function of a specific FLR can be assessed. Various studies concerning these issues have been reported with controversial results. We should also be aware that different strategies and management are required for different types of liver damage, such as cirrhosis in hepatocellular carcinoma, cholangitis in biliary tract cancer, and chemotherapy-induced hepatic injury.
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Platelets Boost Recruitment of CD133 + Bone Marrow Stem Cells to Endothelium and the Rodent Liver-The Role of P-Selectin/PSGL-1 Interactions. Int J Mol Sci 2020; 21:ijms21176431. [PMID: 32899390 PMCID: PMC7504029 DOI: 10.3390/ijms21176431] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 08/28/2020] [Accepted: 08/31/2020] [Indexed: 02/06/2023] Open
Abstract
We previously demonstrated that clinical administration of mobilized CD133+ bone marrow stem cells (BMSC) accelerates hepatic regeneration. Here, we investigated the potential of platelets to modulate CD133+BMSC homing to hepatic endothelial cells and sequestration to warm ischemic livers. Modulatory effects of platelets on the adhesion of CD133+BMSC to human and mouse liver-sinusoidal- and micro- endothelial cells (EC) respectively were evaluated in in vitro co-culture systems. CD133+BMSC adhesion to all types of EC were increased in the presence of platelets under shear stress. This platelet effect was mostly diminished by antagonization of P-selectin and its ligand P-Selectin-Glyco-Ligand-1 (PSGL-1). Inhibition of PECAM-1 as well as SDF-1 receptor CXCR4 had no such effect. In a model of the isolated reperfused rat liver subsequent to warm ischemia, the co-infusion of platelets augmented CD133+BMSC homing to the injured liver with heightened transmigration towards the extra sinusoidal space when compared to perfusion conditions without platelets. Extravascular co-localization of CD133+BMSC with hepatocytes was confirmed by confocal microscopy. We demonstrated an enhancing effect of platelets on CD133+BMSC homing to and transmigrating along hepatic EC putatively depending on PSGL-1 and P-selectin. Our insights suggest a new mechanism of platelets to augment stem cell dependent hepatic repair.
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31
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Amygdalos I, Czigany Z, Bednarsch J, Boecker J, Santana DAM, Meister FA, von der Massen J, Liu WJ, Strnad P, Neumann UP, Lurje G. Low Postoperative Platelet Counts Are Associated with Major Morbidity and Inferior Survival in Adult Recipients of Orthotopic Liver Transplantation. J Gastrointest Surg 2020; 24:1996-2007. [PMID: 31388889 DOI: 10.1007/s11605-019-04337-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Accepted: 07/19/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND Platelets (PLT) play an essential functional role in cellular injury and liver regeneration following partial hepatectomy and orthotopic liver transplantation (OLT). Here, we investigated the association of postoperative PLT counts with short- and long-term outcomes in adult OLT recipients. METHODS Three hundred consecutive patients from our prospective OLT database were analyzed retrospectively (May 2010-November 2017). Ninety-day post-OLT complications were graded using the Clavien-Dindo (CD) classification and quantified by the comprehensive complication index (CCI). To determine the prognostic accuracy of PLT counts, the area under the receiver operating characteristic curve (AUROC) was calculated for major complications (CD ≥ 3b). Parametric and non-parametric tests were applied for subgroup analyses. Uni- and multivariable logistic regression analyses were performed to identify risk factors for major complications. Graft and patient survival were analyzed using the Kaplan-Meier method as well as uni- and multivariable Cox regression analyses. RESULTS Postoperative day 6 PLT counts < 70 × 109/L (POD6-70) were identified as the best cutoff for predicting major complications (AUROC = 0.7; p < 0.001; Youden index 0.317). The stratification of patients into low- (n = 113) and high-PLT (n = 187) groups highlighted significant differences in major complications (CCI 68 ± 29 vs. 43 ± 28, p < 0.001); length of hospital and intensive care unit (ICU) stay (53 ± 43 vs. 31 ± 25, p < 0.001; 21 ± 29 vs. 7 ± 11, p < 0.001, respectively) and estimated procedural costs. POD6-70 was associated with inferior 5-year graft survival. Multivariable logistic regression analysis identified POD6-70 as an independent predictor of major complications (odds ratio 2.298, confidence intervals 1.179-4.478, p = 0.015). CONCLUSION In OLT patients, a PLT count on POD6 of less than 70 × 109/L bears a prognostic significance warranting further investigations.
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Affiliation(s)
- Iakovos Amygdalos
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany
| | - Zoltan Czigany
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany
| | - Jan Bednarsch
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany
| | - Joerg Boecker
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany
| | | | - Franziska Alexandra Meister
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany
| | - Jelena von der Massen
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany
| | - Wen-Jia Liu
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany
| | - Pavel Strnad
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Ulf Peter Neumann
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany
- Department of Surgery, Maastricht University Medical Centre (MUMC), Maastricht, Netherlands
| | - Georg Lurje
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
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Takahashi K, Liang C, Oda T, Ohkohchi N. Platelet and liver regeneration after liver surgery. Surg Today 2020; 50:974-983. [PMID: 31720801 DOI: 10.1007/s00595-019-01890-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 08/03/2019] [Indexed: 02/06/2023]
Abstract
The success of liver surgery, including resection and transplantation, is largely dependent on the ability of the liver to regenerate. Despite substantial improvement in surgical techniques and perioperative care, one of the main concerns is post-hepatectomy liver failure and early allograft dysfunction, both of which are associated with impaired liver regeneration. Recent studies have demonstrated the positive role of platelets in promoting liver regeneration and protecting hepatocytes; however, the underlying mechanisms responsible for these effects are not fully understood. In this review, we updated the accumulated evidence of the role of platelets in promoting liver regeneration, with a focus on liver resection and liver transplantation. The goal of these studies was to support the clinical implementation of platelet agents, such as thrombopoietin receptor agonists, to augment liver regeneration after liver surgery. This "platelet therapy" may become a treatment choice for post-hepatectomy liver failure and early allograft dysfunction.
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Affiliation(s)
- Kazuhiro Takahashi
- Department of Surgery, University of Tsukuba, 1-1-1, Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
- Department of Surgery, Mito Central Hospital, 1136-1, Rokutanda-cho, Mito, 311-1135, Japan
| | - Chen Liang
- Department of Surgery, University of Tsukuba, 1-1-1, Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
- Department of Surgery, Mito Central Hospital, 1136-1, Rokutanda-cho, Mito, 311-1135, Japan
| | - Tatsuya Oda
- Department of Surgery, University of Tsukuba, 1-1-1, Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
- Department of Surgery, Mito Central Hospital, 1136-1, Rokutanda-cho, Mito, 311-1135, Japan
| | - Nobuhiro Ohkohchi
- Department of Surgery, University of Tsukuba, 1-1-1, Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan.
- Department of Surgery, Mito Central Hospital, 1136-1, Rokutanda-cho, Mito, 311-1135, Japan.
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Midorikawa Y, Takayama T, Higaki T, Aramaki O, Teramoto K, Yoshida N, Tsuji S, Kanda T, Moriyama M. High platelet count as a poor prognostic factor for liver cancer patients without cirrhosis. Biosci Trends 2020; 14:368-375. [PMID: 32713867 DOI: 10.5582/bst.2020.03230] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
A low platelet count, one of parameters of portal hypertension, is clinically a predictor of postoperative mortality, while platelets induce tumor development during growth factor secretion. In this study, we retrospectively investigated whether high platelet count negatively affects the survival of patients with hepatocellular carcinoma (HCC). Patients undergoing initial and curative resection for HCC were included. Surgical outcomes were compared between the high platelet (platelet count ≥ 20 × 104/μL) and control (< 20 × 104/μL) groups in patients without cirrhosis and between the low platelet (< 10 × 104/μL) and control (≥ 10 × 104/μL) groups in patients with cirrhosis. Among patients without cirrhosis, tumor was larger (P < 0.001) and tumor thrombus was more frequent (P < 0.001) in the high-platelet group than in the control group. After a median follow-up period of 3.1 years (range 0.2-16.2), median overall survival was 6.3 years (95% confidence interval [CI], 5.3-7.8) and 7.6 years (6.6-10.9) in the high-platelet (n = 273) and control (n = 562) groups, respectively (P = 0.027). Among patients with cirrhosis, liver function was worse (P < 0.001) and varices were more frequent (P < 0.001) in the low-platelet group. The median overall survival of patients in the low-platelet group (n = 172) was significantly shorter than that of patients in the control group (n = 275) (4.5 years [95% CI, 3.7-6.0] vs. 5.9 years [4.5-7.5], P = 0.038). Taken together, thrombocytopenia indicates poor prognosis in HCC patients with cirrhosis, while thrombocytosis is a poor prognostic predictor for those without cirrhosis.
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Affiliation(s)
- Yutaka Midorikawa
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Tokio Higaki
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Osamu Aramaki
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Kenichi Teramoto
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Nao Yoshida
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Shingo Tsuji
- Genome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan
| | - Tatsuo Kanda
- Department of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan
| | - Mitsuhiko Moriyama
- Department of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan
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Kusakabe J, Hata K, Tanaka S, Omae K, Okamura Y, Tajima T, Tamaki I, Miyauchi H, Kubota T, Tanaka H, Uemoto S. Prognostic index consisting of early post-transplant variables <2 weeks in adult living-donor liver transplantation. Hepatol Res 2020; 50:741-753. [PMID: 32012392 PMCID: PMC7317571 DOI: 10.1111/hepr.13489] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Revised: 01/21/2020] [Accepted: 01/26/2020] [Indexed: 12/11/2022]
Abstract
AIM Six-month recipient mortality after adult-to-adult living-donor liver transplantation (LDLT) remains high. Early and accurate prediction of recipient outcome and continuous monitoring of recipient severity after surgery are both essential for guiding appropriate care. This study was designed to identify early post-transplant parameters associated with 6-month mortality, and thereby to construct a discriminatory prognostic index (PI). METHODS We retrospectively analyzed 400 consecutive primary adult-to-adult LDLTs in our center (2006-2017). Perioperative variables were comprehensively analyzed for their accuracy in predicting recipient mortality by comparing the area under the receiver operating characteristic (AUROC) of each factor. RESULTS The AUROCs of preoperative predictive factors, for example, Model for End-stage Liver Disease (MELD) score and donor age, were 0.56 and 0.64, respectively, whereas those of post-transplant platelet count (PLT), total bilirubin (T-BIL), and prothrombin time - international normalized ratio (INR) on postoperative day (POD)-7-14 were 0.71/0.84, 0.68/0.82, and 0.71/0.78, respectively. Logistic regression analysis provided a formula: PIPOD-14 = 3.39 + 0.12 × PLTPOD-14 - 0.09 × T-BILPOD-14 - 1.23 × INRPOD-14 , indicating a high AUROC of 0.87. Recipient 6-month survival with PIPOD-14 < 2.38 (n = 173) was 71.7%, whereas that with PIPOD-14 ≥ 2.38 (n = 222) was 97.7% (P < 0.001). The AUROCs of PIPOD-7 were as high as 0.8 in the subgroups with younger donors (<50 years of age), right lobe grafts, ABO-identical/compatible combinations, or low MELD score (<20), indicating usefulness of PI to identify unexpectedly complicated cases within the first week. CONCLUSIONS A novel, post-transplant survival estimator, PI, accurately predicts recipient 6-month mortality within 1-2 weeks after adult LDLT. Daily monitoring of PI could facilitate early interventions including retransplantation in critically ill patients.
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Affiliation(s)
- Jiro Kusakabe
- Department of Surgery, Division of Hepato‐Biliary‐Pancreatic Surgery and TransplantationKyoto University Graduate School of MedicineKyotoJapan
| | - Koichiro Hata
- Department of Surgery, Division of Hepato‐Biliary‐Pancreatic Surgery and TransplantationKyoto University Graduate School of MedicineKyotoJapan
| | - Shiro Tanaka
- Department of Clinical BiostatisticsKyoto University Graduate School of MedicineKyotoJapan
| | - Katsuhiro Omae
- Department of Clinical BiostatisticsKyoto University Graduate School of MedicineKyotoJapan
| | - Yusuke Okamura
- Department of Surgery, Division of Hepato‐Biliary‐Pancreatic Surgery and TransplantationKyoto University Graduate School of MedicineKyotoJapan
| | - Tetsuya Tajima
- Department of Surgery, Division of Hepato‐Biliary‐Pancreatic Surgery and TransplantationKyoto University Graduate School of MedicineKyotoJapan
| | - Ichiro Tamaki
- Department of Surgery, Division of Hepato‐Biliary‐Pancreatic Surgery and TransplantationKyoto University Graduate School of MedicineKyotoJapan
| | - Hidetaka Miyauchi
- Department of Surgery, Division of Hepato‐Biliary‐Pancreatic Surgery and TransplantationKyoto University Graduate School of MedicineKyotoJapan
| | - Toyonari Kubota
- Department of Surgery, Division of Hepato‐Biliary‐Pancreatic Surgery and TransplantationKyoto University Graduate School of MedicineKyotoJapan
| | - Hirokazu Tanaka
- Department of Surgery, Division of Hepato‐Biliary‐Pancreatic Surgery and TransplantationKyoto University Graduate School of MedicineKyotoJapan
| | - Shinji Uemoto
- Department of Surgery, Division of Hepato‐Biliary‐Pancreatic Surgery and TransplantationKyoto University Graduate School of MedicineKyotoJapan
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Balaphas A, Meyer J, Perozzo R, Zeisser-Labouebe M, Berndt S, Turzi A, Fontana P, Scapozza L, Gonelle-Gispert C, Bühler LH. Platelet Transforming Growth Factor-β1 Induces Liver Sinusoidal Endothelial Cells to Secrete Interleukin-6. Cells 2020; 9:1311. [PMID: 32466100 PMCID: PMC7290849 DOI: 10.3390/cells9051311] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 05/17/2020] [Accepted: 05/18/2020] [Indexed: 02/06/2023] Open
Abstract
The roles and interactions of platelets and liver sinusoidal endothelial cells in liver regeneration are unclear, and the trigger that initiates hepatocyte proliferation is unknown. We aimed to identify the key factors released by activated platelets that induce liver sinusoidal endothelial cells to produce interleukin-6 (IL-6), a cytokine implicated in the early phase of liver regeneration. We characterized the releasate of activated platelets inducing the in vitro production of IL-6 by mouse liver sinusoidal endothelial cells and observed that the stimulating factor was a thermolabile protein. Following gel filtration, a single fraction of activated platelet releasate induced a maximal IL-6 secretion by liver sinusoidal endothelial cells (90.2 ± 13.9 versus control with buffer, 9.0 ± 0.8 pg/mL, p < 0.05). Mass spectroscopy analysis of this fraction, followed by in silico processing, resulted in a reduced list of 18 candidates. Several proteins from the list were tested, and only recombinant transforming growth factor β1 (TGF-β1) resulted in an increased IL-6 production up to 242.7 ± 30.5 pg/mL, which was comparable to non-fractionated platelet releasate effect. Using neutralizing anti-TGF-β1 antibody or a TGF-β1 receptor inhibitor, IL-6 production by liver sinusoidal endothelial cells was dramatically reduced. These results support a role of platelet TGF-β1 β1 in the priming phase of liver regeneration.
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Affiliation(s)
- Alexandre Balaphas
- Division of Digestive Surgery, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland;
- Unit of Surgical Research, University of Geneva, Rue Michel-Servet 1, 1206 Geneva, Switzerland
| | - Jeremy Meyer
- Division of Digestive Surgery, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland;
- Unit of Surgical Research, University of Geneva, Rue Michel-Servet 1, 1206 Geneva, Switzerland
| | - Remo Perozzo
- Pharmaceutical Biochemistry Group, School of Pharmaceutical Sciences, University of Geneva, 1211 Geneva, Switzerland; (M.Z.-L.); (L.S.)
- Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1211 Geneva, Switzerland
| | - Magali Zeisser-Labouebe
- Pharmaceutical Biochemistry Group, School of Pharmaceutical Sciences, University of Geneva, 1211 Geneva, Switzerland; (M.Z.-L.); (L.S.)
- Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1211 Geneva, Switzerland
| | - Sarah Berndt
- Regen Lab SA, En Budron b2, 1052 Le Mont-sur-Lausanne, Switzerland; (S.B.); (A.T.)
| | - Antoine Turzi
- Regen Lab SA, En Budron b2, 1052 Le Mont-sur-Lausanne, Switzerland; (S.B.); (A.T.)
| | - Pierre Fontana
- Division of Angiology and Haemostasis, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland;
- Geneva Platelet Group, University of Geneva, Rue Michel-Servet 1, 1206 Genève, Switzerland
| | - Leonardo Scapozza
- Pharmaceutical Biochemistry Group, School of Pharmaceutical Sciences, University of Geneva, 1211 Geneva, Switzerland; (M.Z.-L.); (L.S.)
- Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1211 Geneva, Switzerland
| | - Carmen Gonelle-Gispert
- Faculty of Science and Medicine, Section of Medicine, University of Fribourg, Route Albert-Gockel 1, 1700 Fribourg, Switzerland; (C.G.-G.); (L.H.B.)
| | - Leo H. Bühler
- Faculty of Science and Medicine, Section of Medicine, University of Fribourg, Route Albert-Gockel 1, 1700 Fribourg, Switzerland; (C.G.-G.); (L.H.B.)
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Yamazaki S, Takayama T, Mitsuka Y, Aoki M, Midorikawa Y, Moriguchi M, Higaki T. Platelet recovery correlates parenchymal volume recovery after liver resection. Hepatol Res 2020; 50:620-628. [PMID: 31965697 DOI: 10.1111/hepr.13488] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Revised: 01/06/2020] [Accepted: 01/07/2020] [Indexed: 02/08/2023]
Abstract
AIM Platelet count seems to assess liver function and predict liver regeneration, but factors associated with liver regeneration remain unclear. This study analyzed the relationship between platelet recovery and postresection liver regeneration. METHODS Data from 343 candidates from 1245 consecutive patients with liver resection of more than Couinaud's segments were analyzed. Patients were divided into a low-platelet-recovery rate (LPRR) group (lowest 25%) or a control group on the basis of the platelet recovery rate on postoperative day (POD)7. Data were matched before analysis to adjust for operation scale. Trends in liver functional recovery were assessed, and liver volume recovery and remnant ischemic area was calculated using computed tomography volumetry. Factors predicting liver regeneration were analyzed. RESULTS In 78 matched-pair patients, the all-complications rate (42.3% vs. 26.9%, P = 0.002) and infectious complications rate (21.8% vs. 9.0%, P = 0.027) were significantly higher in the LPRR group than in controls. Trends in liver functional recovery did not differ significantly, whereas significant differences remained for platelet recovery. Parenchyma volume recovery was delayed in the LPRR group from POD7 (84.5% vs. 78.1, P < 0.01) to POD30 (92.5% vs. 85.6, P < 0.01). Platelet recovery rate on POD7 correlated negatively with ischemic liver volume as evaluated on POD2 by computed tomography (r = 0.691). Postoperative ischemic volume on POD2 (5.41 [1.98-11.21], P < 0.001), infectious complications (3.48 [1.44-7.37], P < 0.001), and multiple resection (1.67 [1.10-4.11], P = 0.011) predicted delayed platelet recovery rate on multivariate analysis. CONCLUSION Platelet recovery correlated with liver volume recovery and occurrence of complications. Large ischemic area might negatively impact regeneration after liver resection.
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Affiliation(s)
- Shintaro Yamazaki
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1 Oyaguchikami-machi, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1 Oyaguchikami-machi, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Yusuke Mitsuka
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1 Oyaguchikami-machi, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Masaru Aoki
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1 Oyaguchikami-machi, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Yutaka Midorikawa
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1 Oyaguchikami-machi, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Masamichi Moriguchi
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1 Oyaguchikami-machi, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Tokio Higaki
- Department of Digestive Surgery, Nihon University School of Medicine, 30-1 Oyaguchikami-machi, Itabashi-ku, Tokyo, 173-8610, Japan
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Meyer J, Balaphas A, Combescure C, Morel P, Gonelle-Gispert C, Bühler L. Systematic review and meta-analysis of thrombocytopenia as a predictor of post-hepatectomy liver failure. HPB (Oxford) 2019; 21:1419-1426. [PMID: 30846279 DOI: 10.1016/j.hpb.2019.01.016] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2018] [Revised: 11/22/2018] [Accepted: 01/31/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND We performed a systematic review and meta-analysis to assess whether thrombocytopenia constituted a risk factor for post-hepatectomy liver failure (PHLF). METHODS We searched MEDLINE and EMBASE from inception until February the 17th, 2018 for studies reporting cases of PHLF in patients with and without thrombocytopenia (defined as a platelet count below 100 or 150 (G/l)) and/or platelet counts in patients with and without PHLF. Pooled odd ratios for PHLF, as well as mean difference in platelet counts between patients with and without PHLF, were obtained by random effects models. Robustness was tested by subgroups and leave-one out sensitivity analyses. Heterogeneity was assessed using the Q-test and quantified based on I2 value. RESULTS We included 15 studies representing 3966 patients. Pooled odds ratio for PHLF in thrombocytopenic patients was 3.71 (95% CI: 2.51 to 5.48; I2 = 0%). Pooled odds ratio was 5.53 (95% CI: 2.85 to 10.48) when pooling only studies based on preoperative platelet count, and 3.13 (95% CI: 1.75 to 5.58) when pooling studies including only patients without liver cirrhosis. The pooled mean difference in platelet counts between patients with and without PHLF was -21.2 (G/l) (95% CI: -36.1 to 6.4) in disfavor of patients with PHLF. When pooling only patients with various qualities of liver tissue, the pooled mean difference was 0.6 (G/l) (95% CI: -21.1 to 22.2). CONCLUSION Preoperative and/or postoperative thrombocytopenia constitute significant risk factors for PHLF in cirrhotic and non-cirrhotic patients.
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Affiliation(s)
- Jeremy Meyer
- Division of Digestive Surgery, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, 1205, Genève, Switzerland; Unit of Surgical Research, University of Geneva, Rue Michel-Servet 1, 1205, Genève, Switzerland.
| | - Alexandre Balaphas
- Division of Digestive Surgery, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, 1205, Genève, Switzerland; Unit of Surgical Research, University of Geneva, Rue Michel-Servet 1, 1205, Genève, Switzerland
| | - Christophe Combescure
- Division of Clinical Epidemiology, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, 1205, Genève, Switzerland
| | - Philippe Morel
- Division of Digestive Surgery, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, 1205, Genève, Switzerland; Unit of Surgical Research, University of Geneva, Rue Michel-Servet 1, 1205, Genève, Switzerland
| | - Carmen Gonelle-Gispert
- Unit of Surgical Research, University of Geneva, Rue Michel-Servet 1, 1205, Genève, Switzerland
| | - Léo Bühler
- Division of Digestive Surgery, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, 1205, Genève, Switzerland; Unit of Surgical Research, University of Geneva, Rue Michel-Servet 1, 1205, Genève, Switzerland
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38
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Agopian VG, Harlander-Locke MP, Markovic D, Dumronggittigule W, Xia V, Kaldas FM, Zarrinpar A, Yersiz H, Farmer DG, Hiatt JR, Busuttil RW. Evaluation of Early Allograft Function Using the Liver Graft Assessment Following Transplantation Risk Score Model. JAMA Surg 2019; 153:436-444. [PMID: 29261831 DOI: 10.1001/jamasurg.2017.5040] [Citation(s) in RCA: 116] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Importance Early allograft dysfunction (EAD) following a liver transplant (LT) unequivocally portends adverse graft and patient outcomes, but a widely accepted classification or grading system is lacking. Objective To develop a model for individualized risk estimation of graft failure after LT and then compare the model's prognostic performance with the existing binary EAD definition (bilirubin level of ≥10 mg/dL on postoperative day 7, international normalized ratio of ≥1.6 on postoperative day 7, or aspartate aminotransferase or alanine aminotransferase level of >2000 U/L within the first 7 days) and the Model for Early Allograft Function (MEAF) score. Design, Setting, and Participants This retrospective single-center analysis used a transplant database to identify all adult patients who underwent a primary LT and had data on 10 days of post-LT laboratory variables at the Dumont-UCLA Transplant Center of the David Geffen School of Medicine at UCLA between February 1, 2002, and June 30, 2015. Data collection took place from January 4, 2016, to June 30, 2016. Data analysis was conducted from July 1, 2016, to August 30, 2017. Main Outcomes and Measures Three-month graft failure-free survival. Results Of 2021 patients who underwent primary LT over the study period, 2008 (99.4%) had available perioperative data and were included in the analysis. The median (interquartile range [IQR]) age of recipients was 56 (49-62) years, and 1294 recipients (64.4%) were men. Overall survival and graft-failure-free survival rates were 83% and 81% at year 1, 74% and 71% at year 3, and 69% and 65% at year 5, with an 11.1% (222 recipients) incidence of 3-month graft failure or death. Multivariate factors associated with 3-month graft failure-free survival included post-LT aspartate aminotransferase level, international normalized ratio, bilirubin level, and platelet count, measures of which were used to calculate the Liver Graft Assessment Following Transplantation (L-GrAFT) risk score. The L-GrAFT model had an excellent C statistic of 0.85, with a significantly superior discrimination of 3-month graft failure-free survival compared with the existing EAD definition (C statistic, 0.68; P < .001) and the MEAF score (C statistic, 0.70; P < .001). Compared with patients with lower L-GrAFT risk, LT recipients in the highest 10th percentile of L-GrAFT scores had higher Model for End-Stage Liver Disease scores (median [IQR], 34 [26-40] vs 31 [25-38]; P = .005); greater need for pretransplant hospitalization (56.8% vs 44.8%; P = .003), renal replacement therapy (42.9% vs 30.5%; P < .001), mechanical ventilation (35.8% vs 18.1%; P < .001), and vasopressors (22.9% vs 11.0%; P < .001); longer cold ischemia times (median [IQR], 436 [311-539] vs 401 [302-506] minutes; P = .04); greater intraoperative blood transfusions (median [IQR], 17 [10-26] vs 10 [6-17] units of packed red blood cells; P < .001); and older donors (median [IQR] age, 47 [28-56] vs 41 [25-52] years; P < .001). Conclusions and Relevance The L-GrAFT risk score allows a highly accurate, individualized risk estimation of 3-month graft failure following LT that is more accurate than existing EAD and MEAF scores. Multicenter validation may allow for the adoption of the L-GrAFT as a tool for evaluating the need for a retransplant, for establishing standardized grading of early allograft function across transplant centers, and as a highly accurate clinical end point in translational studies aiming to mitigate ischemia or reperfusion injury by modulating donor quality and recipient factors.
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Affiliation(s)
- Vatche G Agopian
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles
| | - Michael P Harlander-Locke
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles
| | | | - Wethit Dumronggittigule
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles.,Department of Surgery, Faculty of Medicine, Siriraj Hospital, Mahidol University, Salaya, Thailand
| | - Victor Xia
- Department of Anesthesia, David Geffen School of Medicine at UCLA, Los Angeles
| | - Fady M Kaldas
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles
| | - Ali Zarrinpar
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles
| | - Hasan Yersiz
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles
| | - Douglas G Farmer
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles
| | - Jonathan R Hiatt
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles
| | - Ronald W Busuttil
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles
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Peng W, Li JW, Zhang XY, Li C, Wen TF, Yan LN, Yang JY. A novel model for predicting posthepatectomy liver failure in patients with hepatocellular carcinoma. PLoS One 2019; 14:e0219219. [PMID: 31269063 PMCID: PMC6608969 DOI: 10.1371/journal.pone.0219219] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 06/19/2019] [Indexed: 02/06/2023] Open
Abstract
Posthepatectomy liver failure (PHLF) is the most leading cause of mortality following hepatectomy in patients with hepatocellular carcinoma (HCC). Platelet count was reported to be a simple but useful indicator of liver cirrhosis and function of spleen. Spleen stiffness (SS) was used to evaluate the morphological change of spleen and was reported to be related to liver cirrhosis and portal hypertension. However, the predictive value of platelet to spleen stiffness ratio (PSR) on PHLF remains unknown. A retrospective study was performed to analyze 158 patients with HCC following hepatectomy from August 2015 to February 2016. Univariate and multivariate analyses were performed to evaluate the value of each risk factor for predicting PHLF. The predictive efficiency of the risk factors was evaluated by receiver operating characteristic (ROC) curve. PHLF occured in 23 (14.6%) patients. PSR (P<0.001, odds ratio (OR) = 0.622, 95% confidence interval (CI) 0.493~0.784), hepatic inflow occlusion (HIO) (P = 0.003, OR = 1.044, 95% CI 1.015~1.075) and major hepatectomy (P = 0.019, OR = 5.967, 95% CI 1.346~26.443) were demonstrated to be the independent predictive factors for development of PHLF in a multivariate analysis. Results of the present study suggested PSR is a novel and non-invasive model for predicting PHLF in patients with HCC.
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Affiliation(s)
- Wei Peng
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Jia-Wu Li
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Xiao-Yun Zhang
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Chuan Li
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
- * E-mail:
| | - Tian-Fu Wen
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Lv-Nan Yan
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Jia-Yin Yang
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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40
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Duhme C, Lehwald N, Kehrel BE, Bauchrowitz E, Ngepi A, Schmelzle M, Kolokotronis T, Benhidjeb T, Krüger M, Jurk K, Knoefel WT, Robson SC, Schulte Am Esch J. CD133 + bone marrow stem cells (BMSC) control platelet activation - Role of ectoNTPDase-1 (CD39). Blood Cells Mol Dis 2019; 77:142-148. [PMID: 31075617 DOI: 10.1016/j.bcmd.2019.04.012] [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: 01/29/2019] [Revised: 04/25/2019] [Accepted: 04/26/2019] [Indexed: 01/15/2023]
Abstract
BACKGROUND We previously demonstrated CD133+ bone marrow stem cells (BMSC) to promote hepatic proliferation for liver regeneration. Here, we evaluated the capacity of CD133+BMSC to utilize platelets for homing to vasculature and concomitant controlling their aggregability upon ADP stimulation. METHODS CD133+BMSC and platelets were co-cultured along micro endothelial cells under variable flow conditions and tested for homing levels along vasculature. Aggregometry and FACS analysis were utilized to evaluate platelet reactivity following co-incubation ± CD133+BMSC. RT-PCR and FACS analyses served to characterize ADP degrading ectonucleoside triphosphate diphosphohydrolase-1 (ectoNTPDase-1/CD39) expression on various cell types. RESULTS Platelets attracted human CD133+BMSC to autologous micro endothelium under shear stress unaffected by ADP stimulation. However, CD133+BMSC inhibited ADP-mediated platelet activation and aggregation. Latter was dependent on ectoNTPDase-1 expression levels. Platelet aggregatory control was increased with CD133+BMSC compared to CD133+PHSC. Different effects of those stem cell subtypes positively correlated with their FACS-detected expression levels of ectoNTPDase-1. CONCLUSION We provide evidence that CD133+BMSC are capable of controlling ADP-dependent platelet aggregation and activation by direct interaction dependent on cellular expression of ectoNTPDase-1. Whether different capacities of BMSC modulate platelet-depending thrombogenicity at sites of regeneration impact effectiveness and adverse event profiles of regenerative treatment requires further evaluation.
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Affiliation(s)
- Constanze Duhme
- Department of Surgery A, University Hospital Duesseldorf, Germany
| | - Nadja Lehwald
- Department of Surgery A, University Hospital Duesseldorf, Germany
| | - Beate E Kehrel
- Department of Anesthesiology Intensive Care and Pain Medicine, Experimental and Clinical Hemostasis, University of Muenster, Muenster, Germany
| | | | - Arlette Ngepi
- Department of Surgery A, University Hospital Duesseldorf, Germany
| | | | - Theodoros Kolokotronis
- Center of Visceral Medicine, Department of General and Visceral Surgery, Protestant Hospital of Bethel Foundation, Bielefeld, Germany
| | - Tahar Benhidjeb
- Center of Visceral Medicine, Department of General and Visceral Surgery, Protestant Hospital of Bethel Foundation, Bielefeld, Germany
| | - Martin Krüger
- Center of Visceral Medicine, Department of Gastroenterology and Internal Medicine, Protestant Hospital of Bethel Foundation, Bielefeld, Germany
| | - Kerstin Jurk
- Department of Anesthesiology Intensive Care and Pain Medicine, Experimental and Clinical Hemostasis, University of Muenster, Muenster, Germany; Center for Thrombosis and Hemostasis, Johannes Gutenberg-University, Mainz, Germany
| | | | - Simon C Robson
- The Transplant Institute and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
| | - Jan Schulte Am Esch
- Center of Visceral Medicine, Department of General and Visceral Surgery, Protestant Hospital of Bethel Foundation, Bielefeld, Germany.
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Sonbare DJ. Comment on "Predicting Outcome Early in Living Donor Liver Transplantation: Complex Interplay of Patient Factors, Variables, and the Intended Outcome". Ann Surg 2019; 269:e78-e79. [PMID: 31082928 DOI: 10.1097/sla.0000000000002991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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42
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Alkozai EM, Mahmoodi BK, Decruyenaere J, Porte RJ, Oude Lansink-Hartgring A, Lisman T, Nijsten MW. Systematic comparison of routine laboratory measurements with in-hospital mortality: ICU-Labome, a large cohort study of critically ill patients. Clin Chem Lab Med 2019; 56:1140-1151. [PMID: 29306908 DOI: 10.1515/cclm-2016-1028] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2016] [Accepted: 11/23/2017] [Indexed: 02/03/2023]
Abstract
BACKGROUND In intensive care unit (ICU) patients, many laboratory measurements can be deranged when compared with the standard reference interval (RI). The assumption that larger derangements are associated with worse outcome may not always be correct. The ICU-Labome study systematically evaluated the univariate association of routine laboratory measurements with outcome. METHODS We studied the 35 most frequent blood-based measurements in adults admitted ≥6 h to our ICU between 1992 and 2013. Measurements were from the first 14 ICU days and before ICU admission. Various metrics, including variability, were related with hospital survival. ICU- based RIs were derived from measurements obtained at ICU discharge in patients who were not readmitted to the ICU and survived for >1 year. RESULTS In 49,464 patients (cardiothoracic surgery 43%), we assessed >20·106 measurements. ICU readmissions, in-hospital and 1-year mortality were 13%, 14% and 19%, respectively. On ICU admission, lactate had the strongest relation with hospital mortality. Variability was independently related with hospital mortality in 30 of 35 measurements, and 16 of 35 measurements displayed a U-shaped outcome-relation. Medians of 14 of 35 ICU-based ranges were outside the standard RI. Remarkably, γ-glutamyltransferase (GGT) had a paradoxical relation with hospital mortality in the second ICU week because more abnormal GGT-levels were observed in hospital survivors. CONCLUSIONS ICU-based RIs for may be more useful than standard RIs in identifying ICU patients at risk. The association of variability with outcome for most of the measurements suggests this is a consequence and not a cause of a worse ICU outcome. Late elevation of GGT may confer protection to ICU patients.
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Affiliation(s)
- Edris M Alkozai
- Department of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, TheNetherlands.,Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, TheNetherlands
| | | | - Johan Decruyenaere
- Department of Intensive Care Medicine, Ghent University Hospital, Ghent, Belgium
| | - Robert J Porte
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, TheNetherlands
| | | | - Ton Lisman
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, TheNetherlands
| | - Maarten W Nijsten
- Department of Critical Care, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands, Phone: 00-31-50-3616161, Fax: 0031-50-3615644
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Zhang L, Yao W, Xia J, Wang T, Huang F. Glucagon-Induced Acetylation of Energy-Sensing Factors in Control of Hepatic Metabolism. Int J Mol Sci 2019; 20:ijms20081885. [PMID: 30995792 PMCID: PMC6515121 DOI: 10.3390/ijms20081885] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 04/04/2019] [Accepted: 04/10/2019] [Indexed: 12/15/2022] Open
Abstract
The liver is the central organ of glycolipid metabolism, which regulates the metabolism of lipids and glucose to maintain energy homeostasis upon alterations of physiological conditions. Researchers formerly focused on the phosphorylation of glucagon in controlling liver metabolism. Noteworthily, emerging evidence has shown glucagon could additionally induce acetylation to control hepatic metabolism in response to different physiological states. Through inducing acetylation of complex metabolic networks, glucagon interacts extensively with various energy-sensing factors in shifting from glucose metabolism to lipid metabolism during prolonged fasting. In addition, glucagon-induced acetylation of different energy-sensing factors is involved in the advancement of nonalcoholic fatty liver disease (NAFLD) to liver cancer. Here, we summarize the latest findings on glucagon to control hepatic metabolism by inducing acetylation of energy-sensing factors. Finally, we summarize and discuss the potential impact of glucagon on the treatment of liver diseases.
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Affiliation(s)
- Li Zhang
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
| | - Weilei Yao
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
| | - Jun Xia
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
| | - Tongxin Wang
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
| | - Feiruo Huang
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
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Intrahepatic fibrin(ogen) deposition drives liver regeneration after partial hepatectomy in mice and humans. Blood 2019; 133:1245-1256. [PMID: 30655274 DOI: 10.1182/blood-2018-08-869057] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Accepted: 01/09/2019] [Indexed: 02/06/2023] Open
Abstract
Platelets play a pivotal role in stimulating liver regeneration after partial hepatectomy in rodents and humans. Liver regeneration in rodents is delayed when platelets are inhibited. However, the exact mechanisms whereby platelets accumulate and promote liver regeneration remain uncertain. Thrombin-dependent intrahepatic fibrin(ogen) deposition was recently reported after partial hepatectomy (PHx) in mice, but the role of fibrin(ogen) deposits in liver regeneration has not been investigated. We tested the hypothesis that fibrin(ogen) contributes to liver regeneration by promoting intrahepatic platelet accumulation and identified the trigger of rapid intrahepatic coagulation after PHx. PHx in wild-type mice triggered rapid intrahepatic coagulation, evidenced by intrahepatic fibrin(ogen) deposition. Intrahepatic fibrin(ogen) deposition was abolished in mice with liver-specific tissue factor deficiency, pinpointing the trigger of coagulation after PHx. Direct thrombin activation of platelets through protease-activated receptor-4 did not contribute to hepatocyte proliferation after PHx, indicating that thrombin contributes to liver regeneration primarily by driving intrahepatic fibrin(ogen) deposition. Fibrinogen depletion with ancrod reduced both intrahepatic platelet accumulation and hepatocyte proliferation after PHx, indicating that fibrin(ogen) contributes to liver regeneration after PHx by promoting intrahepatic platelet accumulation. Consistent with the protective function of fibrin(ogen) in mice, low postoperative plasma fibrinogen levels were associated with liver dysfunction and mortality in patients undergoing liver resection. Moreover, increased intrahepatic fibrin(ogen) deposition was evident in livers of patients after liver resection but was remarkably absent in patients displaying hepatic dysfunction postresection. The results suggest a novel mechanism whereby coagulation-dependent intrahepatic fibrin(ogen) deposition drives platelet accumulation and liver regeneration after PHx.
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Aryal B, Yamakuchi M, Shimizu T, Kadono J, Furoi A, Gejima K, Komokata T, Hashiguchi T, Imoto Y. Therapeutic implication of platelets in liver regeneration -hopes and hues. Expert Rev Gastroenterol Hepatol 2018; 12:1219-1228. [PMID: 30791793 DOI: 10.1080/17474124.2018.1533813] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Mounting evidence highlights platelet involvement in liver regeneration via interaction with liver cells, growth factors release, and signaling contributions. Existing research suggests a compelling biological rationale for utilizing platelet biology, with the goal of improving liver function and accelerating its regenerative potential. Despite its expanding application in several clinical areas, the contribution of the platelet and its therapeutic implementation in liver regeneration so far has not yet fulfilled the initial high expectations. Areas covered: This review scrutinizes the progress, current updates, and discusses how recent understanding - particularly in the clinical implications of platelet-based therapy - may enable strategies to introduce and harness the therapeutic potential of the platelet during liver regeneration. Expert commentary: Several clinical and translational studies have facilitated a platform for the development of platelet-based therapy to enhance liver regeneration. While some of these therapies are effective to augment liver regeneration, the others have had some detrimental outcomes. The existing evidence represents a challenge for future projects that are focused on directly incorporating platelet-based therapies to induce liver regeneration.
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Affiliation(s)
- Bibek Aryal
- a Cardiovascular and Gastroenterological Surgery, Graduate School of Medical and Dental Sciences , Kagoshima University , Kagoshima , Japan
| | - Munekazu Yamakuchi
- b Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences , Kagoshima University , Kagoshima , Japan
| | - Toshiaki Shimizu
- b Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences , Kagoshima University , Kagoshima , Japan
| | - Jun Kadono
- c Department of Surgery , Kirishima Medical Center , Kirishima , Japan
| | - Akira Furoi
- c Department of Surgery , Kirishima Medical Center , Kirishima , Japan
| | - Kentaro Gejima
- a Cardiovascular and Gastroenterological Surgery, Graduate School of Medical and Dental Sciences , Kagoshima University , Kagoshima , Japan
| | - Teruo Komokata
- d Department of Surgery , Kagoshima Medical Center . Kagoshima , Japan
| | - Teruto Hashiguchi
- b Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences , Kagoshima University , Kagoshima , Japan
| | - Yutaka Imoto
- a Cardiovascular and Gastroenterological Surgery, Graduate School of Medical and Dental Sciences , Kagoshima University , Kagoshima , Japan
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Elevated ADAMTS13 Activity is Associated with Poor Postoperative Outcome in Patients Undergoing Liver Resection. Sci Rep 2018; 8:16823. [PMID: 30429491 PMCID: PMC6235878 DOI: 10.1038/s41598-018-34794-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2018] [Accepted: 10/19/2018] [Indexed: 02/08/2023] Open
Abstract
Recently, von-Willebrand-Factor (vWF) has been shown to correlate with postoperative liver dysfunction (LD). Accordingly, “disintegrin-like metalloprotease with thrombospondin type1 motif” (ADAMTS13) is known to cleave vWF in less active fragments. Thus, we aimed to evaluate the diagnostic potential of ADAMTS13-activity (ADAMTS13-AC) to identify patients with postoperative LD after hepatectomy. Accordingly 37 patients undergoing hepatectomy for different neoplastic entities were included in this study. Plasma ADAMTS13-AC and vWF-Ag were measured 1 day prior to (preOP), 1 and 5 days (POD1/5) after hepatectomy. In accordance to the ISGLS-criteria LD was prospectively recorded. In this context, perioperative ADAMTS13-AC- and vWF-Ag/ADAMTS13-AC-ratio- levels revealed a significant increase after hepatectomy. Accordingly, elevated vWF-Ag/ADAMTS13-AC-ratio significantly predicted LD (preOP AUC: 0.75, p = 0.02; POD1 AUC: 0.80, p = 0.03). Patients who fulfilled our perioperative vWF-Ag/ADAMTS13-AC-ratio cut-off-levels (preOP: ≥116, POD1: ≥165) suffered from significantly higher incidences of LD (preOP: 70% vs. 30%, p = 0.01; POD1: 83% vs. 17%, p = 0.001). In conclusion, perioperative ADAMTS13-AC measurement may serve as a useful parameter to early detect high-risk patients developing postoperative LD prior to liver resection in patients suffering from hepatic malignancies. Indeed, further investigations have to be performed to consolidate its role as a predictive marker for LD.
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Golriz M, Ghamarnejad O, Khajeh E, Sabagh M, Mieth M, Hoffmann K, Ulrich A, Hackert T, Weiss KH, Schirmacher P, Büchler MW, Mehrabi A. Preoperative Thrombocytopenia May Predict Poor Surgical Outcome after Extended Hepatectomy. Can J Gastroenterol Hepatol 2018; 2018:1275720. [PMID: 30515369 PMCID: PMC6236772 DOI: 10.1155/2018/1275720] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Revised: 06/12/2018] [Accepted: 06/27/2018] [Indexed: 12/12/2022] Open
Abstract
Background It is a novel idea that platelet counts may be associated with postoperative outcome following liver surgery. This may help in planning an extended hepatectomy (EH), which is a surgical procedure with high morbidity and mortality. Aim The aim of this study was to evaluate the predictive potential of platelet counts on the outcome of EH in patients without portal hypertension, splenomegaly, or cirrhosis. Methods A series of 213 consecutive patients underwent EH (resection of ≥ five liver segments) between 2001 and 2016. The association of preoperative platelet counts with posthepatectomy liver failure (PHLF), morbidity (based on Clavien-Dindo classification), and 30-day mortality was evaluated using multivariate analysis. Results PHLF was detected in 26.3% of patients, major complications in 26.8%, and 30-day mortality in 11.3% of patients. Multivariate analysis revealed that the preoperative platelet count is an independent predictor of PHLF (odds ratio [OR] 4.4, 95% confidence interval [CI] 1.3-15.0, p=0.020) and 30-day mortality (OR 4.4, 95% CI 1.1-18.8, p=0.043). Conclusions Preoperative platelet count is associated with PHLF and mortality following extended liver resection. This association was independent of other related parameters. Prospective studies are needed to evaluate the predictive role and to determine the impact of preoperative correction of platelet count on postoperative outcomes after EH.
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Affiliation(s)
- Mohammad Golriz
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Omid Ghamarnejad
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Elias Khajeh
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Mohammadsadegh Sabagh
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Markus Mieth
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Katrin Hoffmann
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Alexis Ulrich
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Thilo Hackert
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Karl Heinz Weiss
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
- Department of Gastroenterology and Hepatology, University of Heidelberg, Heidelberg, Germany
| | - Peter Schirmacher
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
- Institute of Pathology, University of Heidelberg, Heidelberg, Germany
| | - Markus W. Büchler
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
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Eyraud D, Suner L, Dupont A, Bachelot-Loza C, Smadja DM, Helley D, Bertil S, Gostian O, Szymezak J, Loncar Y, Puybasset L, Lebray P, Vezinet C, Vaillant JC, Granger B, Gaussem P. Evolution of platelet functions in cirrhotic patients undergoing liver transplantation: A prospective exploration over a month. PLoS One 2018; 13:e0200364. [PMID: 30071043 PMCID: PMC6072007 DOI: 10.1371/journal.pone.0200364] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Accepted: 06/25/2018] [Indexed: 12/23/2022] Open
Abstract
This prospective observational study was designed to analyze platelet functions across time in 50 patients scheduled for liver transplantation (LT) secondary to decompensated cirrhosis or hepatocellular carcinoma. Platelet functions were assessed before LT (pre-LT), one week (D7) and 1 month (D28) after LT. Platelet count significantly increased from pre-LT time to day 28 as well as circulating CD34+hematopoietic stem cells. To avoid any influence of platelet count on assays, platelet function was evaluated on platelet-rich-plasma adjusted to pre-LT platelet count. Although platelet secretion potential did not differ between time-points, as evaluated by the expression of CD62P upon strong activation, platelet aggregation in response to various agonists significantly increased along time, however with no concomitant increase of circulating markers of platelet activation: platelet microvesicles, platelet-leukocyte complexes, soluble CD40L and soluble CD62P. In the multivariate analysis, hepatic function was associated with platelet count and function. A lower platelet aggregation recovery was correlated with Child C score. History of thrombosis or bleeding was associated with respective higher or lower values of platelet aggregation. This longitudinal analysis of platelet functions in LT patients showed an improvement of platelet functions along time together with platelet count increase, with no evidence of platelet hyperactivation at any time-point.
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Affiliation(s)
- Daniel Eyraud
- AP-HP, Pitié-Salpêtrière University Hospital, Department of Anesthesiology and Reanimation, Paris, France
- AP-HP, Pitié-Salpêtrière University Hospital, Department of Digestive, HPB Surgery, and Liver Transplantation, Paris, France
- Université Pierre et Marie Curie, Paris, France
| | - Ludovic Suner
- AP-HP, European University Hospital Georges Pompidou, Hematology Department, Paris, France
| | - Axelle Dupont
- Université Pierre et Marie Curie, Paris, France
- AP-HP, Pitié-Salpêtrière University Hospital, Department of statistics, Clinical Research Unit, Paris, France
| | - Christilla Bachelot-Loza
- Inserm UMR-S1140, Faculté de Pharmacie, Paris, France
- Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - David M. Smadja
- AP-HP, European University Hospital Georges Pompidou, Hematology Department, Paris, France
- Inserm UMR-S1140, Faculté de Pharmacie, Paris, France
- Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Dominique Helley
- AP-HP, European University Hospital Georges Pompidou, Hematology Department, Paris, France
- Université Paris Descartes, Sorbonne Paris Cité, Paris, France
- Inserm UMR-S970, Paris, France
| | - Sébastien Bertil
- AP-HP, European University Hospital Georges Pompidou, Hematology Department, Paris, France
| | - Ovidiu Gostian
- AP-HP, Pitié-Salpêtrière University Hospital, Department of Anesthesiology and Reanimation, Paris, France
- Université Pierre et Marie Curie, Paris, France
| | - Jean Szymezak
- AP-HP, European University Hospital Georges Pompidou, Hematology Department, Paris, France
| | - Yann Loncar
- AP-HP, Pitié-Salpêtrière University Hospital, Department of Anesthesiology and Reanimation, Paris, France
- Université Pierre et Marie Curie, Paris, France
| | - Louis Puybasset
- AP-HP, Pitié-Salpêtrière University Hospital, Department of Anesthesiology and Reanimation, Paris, France
- Université Pierre et Marie Curie, Paris, France
| | - Pascal Lebray
- AP-HP, Pitié-Salpêtrière University Hospital, Hepatology Department, Paris, France
| | - Corinne Vezinet
- AP-HP, Pitié-Salpêtrière University Hospital, Department of Anesthesiology and Reanimation, Paris, France
| | - Jean-Christophe Vaillant
- AP-HP, Pitié-Salpêtrière University Hospital, Department of Digestive, HPB Surgery, and Liver Transplantation, Paris, France
- Université Pierre et Marie Curie, Paris, France
| | - Benjamin Granger
- Université Pierre et Marie Curie, Paris, France
- AP-HP, Pitié-Salpêtrière University Hospital, Department of statistics, Clinical Research Unit, Paris, France
| | - Pascale Gaussem
- AP-HP, European University Hospital Georges Pompidou, Hematology Department, Paris, France
- Inserm UMR-S1140, Faculté de Pharmacie, Paris, France
- Université Paris Descartes, Sorbonne Paris Cité, Paris, France
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Mehrabi A, Golriz M, Khajeh E, Ghamarnejad O, Probst P, Fonouni H, Mohammadi S, Weiss KH, Büchler MW. Meta-analysis of the prognostic role of perioperative platelet count in posthepatectomy liver failure and mortality. Br J Surg 2018; 105:1254-1261. [PMID: 29999190 DOI: 10.1002/bjs.10906] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2018] [Revised: 05/08/2018] [Accepted: 05/09/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Emerging evidence suggests that the perioperative platelet count (PLT) can predict posthepatectomy liver failure (PHLF). In this systematic review and meta-analysis, the impact of perioperative PLT on PHLF and mortality was evaluated. METHODS MEDLINE and Web of Science databases were searched systematically for relevant literature up to January 2018. All studies comparing PHLF or mortality in patients with a low versus high perioperative PLT were included. Study quality was assessed using methodological index for non-randomized studies (MINORS) criteria. Meta-analyses were performed using Mantel-Haenszel tests with a random-effects model, and presented as odds ratios (ORs) with 95 per cent confidence intervals. RESULTS Thirteen studies containing 5260 patients were included in the meta-analysis. Two different cut-off values for PLT were used: 150 and 100/nl. Patients with a perioperative PLT below 150/nl had higher PHLF (4 studies, 817 patients; OR 4·79, 95 per cent c.i. 2·89 to 7·94) and mortality (4 studies, 3307 patients; OR 3·78, 1·48 to 9·62) rates than patients with a perioperative PLT of 150/nl or more. Similarly, patients with a PLT below 100/nl had a significantly higher risk of PHLF (4 studies, 949 patients; OR 4·65, 2·60 to 8·31) and higher mortality rates (7 studies, 3487 patients; OR 6·35, 2·99 to 13·47) than patients with a PLT of 100/nl or greater. CONCLUSION A low perioperative PLT correlates with higher PHLF and mortality rates after hepatectomy.
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Affiliation(s)
- A Mehrabi
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - M Golriz
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - E Khajeh
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - O Ghamarnejad
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - P Probst
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.,Study Centre of the German Surgical Society, University of Heidelberg, Heidelberg, Germany
| | - H Fonouni
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - S Mohammadi
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - K H Weiss
- Department of Gastroenterology and Hepatology, University of Heidelberg, Heidelberg, Germany
| | - M W Büchler
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
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50
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Huang L, Yu Q, Wang J. Association Between Changes in Splanchnic Hemodynamics and Risk Factors of Portal Venous System Thrombosis After Splenectomy with Periesophagogastric Devascularization. Med Sci Monit 2018; 24:4355-4362. [PMID: 29937539 PMCID: PMC6048999 DOI: 10.12659/msm.909403] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background The purpose of this study was to investigate splanchnic hemodynamic changes and determine an optimal cutoff value for risk factors of portal venous system thrombosis (PVST) after splenectomy with periesophagogastric devascularization (SPD) in cirrhotic patients with esophageal and gastric variceal bleeding (EGVB) and portal hypertension (PH). Material/Methods Data on patients who underwent SPD were collected retrospectively from January 2013 to December 2017. Color Doppler ultrasound was performed to detect hemodynamic changes of the hepatic artery, splenic artery, splenic vein, and portal vein in included patients (n=60) and healthy volunteers (n=30). Outcomes were compared between preoperative and postoperative biochemical indicators. The cutoff values for hemodynamics were identified using receiver operating characteristic (ROC) curve analysis, and univariate and multivariate analyses of risk factors of PVST were performed. Results In our series, hemodynamic indexes of splenic artery, spleen vein, and portal vein in the study group were significantly higher than that of the control group (P<0.05). Multivariate analysis revealed that the portal vein flow and the internal diameter of the portal vein were significantly correlated with PVST. The ROC analysis revealed that the cutoff points for portal vein flow and internal diameter of the splenic vein and portal vein were ≥1822.32 ml/min, ≥1.37 cm, and ≥1.56 cm, respectively. Conclusions SPD is an effective treatment in cirrhotic patients with concomitant EGVB and PH by increasing hepatic artery flow and decreasing portal vein flow. High portal vein flow and wider diameters of the portal vein and splenic vein are important markers of PVST.
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Affiliation(s)
- Long Huang
- Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China (mainland).,1st Department of Surgery, The First Hospital Affiliated to Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China (mainland)
| | - Qingsheng Yu
- Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China (mainland).,1st Department of Surgery, The First Hospital Affiliated to Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China (mainland)
| | - Jiajia Wang
- 1st Department of Surgery, The First Hospital Affiliated to Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China (mainland)
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