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Rossi AP, Katz-Greenberg G, Coscia L, Brady CW, Doligalski C, Irani RA, Matas A, Shah S, Lentine KL. Living Donation and Pregnancy-Related Complications: State of the Evidence and Call To Action for Improved Risk Assessment. Clin J Am Soc Nephrol 2024; 19:1659-1670. [PMID: 39652653 PMCID: PMC11637692 DOI: 10.2215/cjn.0000000593] [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] [Indexed: 10/18/2024]
Abstract
Living kidney donation and living liver donation significantly increases organ supply to make lifesaving transplants possible, offering survival benefits to the recipients and cost savings to society. Of all living donors, 40% are women of childbearing age. However, limited data exist regarding the effect of donation on future pregnancies and of pregnancy-related complications on postdonation outcomes. In February 2023, the American Society of Transplantation Women's Health Community of Practice held a virtual Controversies Conference on reproductive health, contraception, and pregnancy after transplantation and living donation. Experts in the field presented the available data. Smaller breakout sessions were created to discuss findings, identify knowledge gaps, and develop recommendations. We present the conference findings related to living donation. The evidence reviewed shows that gestational hypertension and gestational diabetes mellitus before kidney donation have been associated with an increased risk of developing postdonation hypertension and diabetes mellitus, respectively, without increasing the risk of developing an eGFR <45 ml/min after donation. The risk of preeclampsia in living kidney donors increases to 4%-10%, and low-dose aspirin may help reduce that risk. Little is known about the financial burden for living donors who become pregnant, their risk of postpartum depression, or the optimal time between donation and conception. The data on living liver donors are even scarcer. The creation of a registry of donor candidates may help answer many of these questions and, in turn, educate prospective donors so that they can make an informed choice.
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Affiliation(s)
| | - Goni Katz-Greenberg
- Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina
| | - Lisa Coscia
- Transplant Pregnancy Registry International, Gift of Life, Philadelphia, Pennsylvania
| | - Carla W. Brady
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina
| | - Christina Doligalski
- Department of Pharmacy, University of North Carolina Hospitals and Clinics, Chapel Hill, North Carolina
| | - Roxanna A. Irani
- Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, California
| | - Arthur Matas
- Division of Transplantation, Department of Surgery, University of Minnesota, Minneapolis, Minnesota
| | - Silvi Shah
- Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio
| | - Krista L. Lentine
- SSM Health Saint Louis University Transplant Center, Saint Louis University School of Medicine, St. Louis, Missouri
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Uriarte I, Santamaria E, López-Pascual A, Monte MJ, Argemí J, Latasa MU, Adán-Villaescusa E, Irigaray A, Herranz JM, Arechederra M, Basualdo J, Lucena F, Corrales FJ, Rotellar F, Pardo F, Merlen G, Rainteau D, Sangro B, Tordjmann T, Berasain C, Marín JJG, Fernández-Barrena MG, Herrero I, Avila MA. New insights into the regulation of bile acids synthesis during the early stages of liver regeneration: A human and experimental study. Biochim Biophys Acta Mol Basis Dis 2024; 1870:167166. [PMID: 38642480 DOI: 10.1016/j.bbadis.2024.167166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 04/04/2024] [Accepted: 04/08/2024] [Indexed: 04/22/2024]
Abstract
BACKGROUND AND AIMS Liver regeneration is essential for the preservation of homeostasis and survival. Bile acids (BAs)-mediated signaling is necessary for liver regeneration, but BAs levels need to be carefully controlled to avoid hepatotoxicity. We studied the early response of the BAs-fibroblast growth factor 19 (FGF19) axis in healthy individuals undergoing hepatectomy for living donor liver transplant. We also evaluated BAs synthesis in mice upon partial hepatectomy (PH) and acute inflammation, focusing on the regulation of cytochrome-7A1 (CYP7A1), a key enzyme in BAs synthesis from cholesterol. METHODS Serum was obtained from twelve human liver donors. Mice underwent 2/3-PH or sham-operation. Acute inflammation was induced with bacterial lipopolysaccharide (LPS) in mice fed control or antoxidant-supplemented diets. BAs and 7α-hydroxy-4-cholesten-3-one (C4) levels were measured by HPLC-MS/MS; serum FGF19 by ELISA. Gene expression and protein levels were analyzed by RT-qPCR and western-blot. RESULTS Serum BAs levels increased after PH. In patients with more pronounced hypercholanemia, FGF19 concentrations transiently rose, while C4 levels (a readout of CYP7A1 activity) dropped 2 h post-resection in all cases. Serum BAs and C4 followed the same pattern in mice 1 h after PH, but C4 levels also dropped in sham-operated and LPS-treated animals, without marked changes in CYP7A1 protein levels. LPS-induced serum C4 decline was attenuated in mice fed an antioxidant-supplemented diet. CONCLUSIONS In human liver regeneration FGF19 upregulation may constitute a protective response from BAs excess during liver regeneration. Our findings suggest the existence of post-translational mechanisms regulating CYP7A1 activity, and therefore BAs synthesis, independent from CYP7A1/Cyp7a1 gene transcription.
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Affiliation(s)
- Iker Uriarte
- Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Eva Santamaria
- Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Amaya López-Pascual
- Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain; Instituto de Investigaciones Sanitarias de Navarra IdiSNA, Pamplona, Spain
| | - María J Monte
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Université Paris-Saclay, Inserm U1193, Orsay, France
| | - Josepmaria Argemí
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigaciones Sanitarias de Navarra IdiSNA, Pamplona, Spain; Hepatology Unit, CCUN, Navarra University Clinic, Pamplona, Spain
| | - M Ujue Latasa
- Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain; Instituto de Investigaciones Sanitarias de Navarra IdiSNA, Pamplona, Spain
| | - Elena Adán-Villaescusa
- Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain
| | - Ainara Irigaray
- Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain
| | - Jose M Herranz
- Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - María Arechederra
- Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigaciones Sanitarias de Navarra IdiSNA, Pamplona, Spain
| | - Jorge Basualdo
- Hepatology Unit, CCUN, Navarra University Clinic, Pamplona, Spain; Internal Medicine Department, ICOT Hospital Ciudad de Telde, Las Palmas, Spain
| | - Felipe Lucena
- Internal Medicine Department, Navarra University Clinic, Pamplona, Spain
| | - Fernando J Corrales
- Functional Proteomics Laboratory, Centro Nacional de Biotecnología (CSIC), Madrid, Spain
| | - Fernando Rotellar
- General Surgery Department, Navarra University Clinic, Pamplona, Spain
| | - Fernando Pardo
- General Surgery Department, Navarra University Clinic, Pamplona, Spain
| | | | - Dominique Rainteau
- Sorbonne Université, Inserm U938, Centre de Recherche Saint-Antoine, Paris, France
| | - Bruno Sangro
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigaciones Sanitarias de Navarra IdiSNA, Pamplona, Spain; Hepatology Unit, CCUN, Navarra University Clinic, Pamplona, Spain
| | | | - Carmen Berasain
- Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Jose J G Marín
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Experimental Hepatology and Drug Targeting (HEVEPHARM), University of Salamanca, IBSAL, Salamanca, Spain
| | - Maite G Fernández-Barrena
- Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigaciones Sanitarias de Navarra IdiSNA, Pamplona, Spain
| | - Ignacio Herrero
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigaciones Sanitarias de Navarra IdiSNA, Pamplona, Spain; Hepatology Unit, CCUN, Navarra University Clinic, Pamplona, Spain.
| | - Matias A Avila
- Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigaciones Sanitarias de Navarra IdiSNA, Pamplona, Spain.
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Takahashi K, Gosho M, Miyazaki Y, Nakahashi H, Shimomura O, Furuya K, Doi M, Owada Y, Ogawa K, Ohara Y, Akashi Y, Enomoto T, Hashimoto S, Oda T. Preoperative albumin-bilirubin score and liver resection percentage determine postoperative liver regeneration after partial hepatectomy. World J Gastroenterol 2024; 30:2006-2017. [PMID: 38681122 PMCID: PMC11045494 DOI: 10.3748/wjg.v30.i14.2006] [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: 12/07/2023] [Revised: 02/05/2024] [Accepted: 03/25/2024] [Indexed: 04/12/2024] Open
Abstract
BACKGROUND The success of liver resection relies on the ability of the remnant liver to regenerate. Most of the knowledge regarding the pathophysiological basis of liver regeneration comes from rodent studies, and data on humans are scarce. Additionally, there is limited knowledge about the preoperative factors that influence postoperative regeneration. AIM To quantify postoperative remnant liver volume by the latest volumetric software and investigate perioperative factors that affect posthepatectomy liver regeneration. METHODS A total of 268 patients who received partial hepatectomy were enrolled. Patients were grouped into right hepatectomy/trisegmentectomy (RH/Tri), left hepatectomy (LH), segmentectomy (Seg), and subsegmentectomy/nonanatomical hepatectomy (Sub/Non) groups. The regeneration index (RI) and late regeneration rate were defined as (postoperative liver volume)/[total functional liver volume (TFLV)] × 100 and (RI at 6-months - RI at 3-months)/RI at 6-months, respectively. The lower 25th percentile of RI and the higher 25th percentile of late regeneration rate in each group were defined as "low regeneration" and "delayed regeneration". "Restoration to the original size" was defined as regeneration of the liver volume by more than 90% of the TFLV at 12 months postsurgery. RESULTS The numbers of patients in the RH/Tri, LH, Seg, and Sub/Non groups were 41, 53, 99 and 75, respectively. The RI plateaued at 3 months in the LH, Seg, and Sub/Non groups, whereas the RI increased until 12 months in the RH/Tri group. According to our multivariate analysis, the preoperative albumin-bilirubin (ALBI) score was an independent factor for low regeneration at 3 months [odds ratio (OR) 95%CI = 2.80 (1.17-6.69), P = 0.02; per 1.0 up] and 12 months [OR = 2.27 (1.01-5.09), P = 0.04; per 1.0 up]. Multivariate analysis revealed that only liver resection percentage [OR = 1.03 (1.00-1.05), P = 0.04] was associated with delayed regeneration. Furthermore, multivariate analysis demonstrated that the preoperative ALBI score [OR = 2.63 (1.00-1.05), P = 0.02; per 1.0 up] and liver resection percentage [OR = 1.02 (1.00-1.05), P = 0.04; per 1.0 up] were found to be independent risk factors associated with volume restoration failure. CONCLUSION Liver regeneration posthepatectomy was determined by the resection percentage and preoperative ALBI score. This knowledge helps surgeons decide the timing and type of rehepatectomy for recurrent cases.
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Affiliation(s)
- Kazuhiro Takahashi
- Department of Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058-575, Ibaraki, Japan
| | - Masahiko Gosho
- Department of Biostatistics, University of Tsukuba, Tsukuba 3058-575, Ibaraki, Japan
| | - Yoshihiro Miyazaki
- Department of Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058-575, Ibaraki, Japan
| | - Hiromitsu Nakahashi
- Department of Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058-575, Ibaraki, Japan
| | - Osamu Shimomura
- Department of Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058-575, Ibaraki, Japan
| | - Kinji Furuya
- Department of Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058-575, Ibaraki, Japan
| | - Manami Doi
- Department of Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058-575, Ibaraki, Japan
| | - Yohei Owada
- Department of Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058-575, Ibaraki, Japan
| | - Koichi Ogawa
- Department of Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058-575, Ibaraki, Japan
| | - Yusuke Ohara
- Department of Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058-575, Ibaraki, Japan
| | - Yoshimasa Akashi
- Department of Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058-575, Ibaraki, Japan
| | - Tsuyoshi Enomoto
- Department of Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058-575, Ibaraki, Japan
| | - Shinji Hashimoto
- Department of Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058-575, Ibaraki, Japan
| | - Tatsuya Oda
- Department of Gastrointestinal and Hepatobiliary-Pancreatic Surgery, University of Tsukuba, Tsukuba 3058-575, Ibaraki, Japan
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Shah BS, Sabnis GR, Kumar D, Lanjewar C. Platypnea-orthodeoxia syndrome (POS) in a patient who had undergone partial liver resection. BMJ Case Rep 2024; 17:e258755. [PMID: 38331445 PMCID: PMC10860005 DOI: 10.1136/bcr-2023-258755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/28/2024] [Indexed: 02/10/2024] Open
Abstract
A South Asian male in his early 60s presented with acute-onset dyspnoea on postoperative day 4 after undergoing middle hepatic vein sacrificing partial liver resection for epithelioid angiomyolipoma. The patient's SpO2 on presentation was 65% in standing position which improved to 90% in left lateral decubitus. He was suspected of having platypnea-orthodeoxia syndrome (POS) which was confirmed on echocardiogram with microbubble contrast showing a large intracardiac right-to-left shunt. The patient was taken up for transcatheter closure of patent foramen ovale (PFO). A 30 mm Amplatzer PFO Occluder was deployed across the PFO which reduced the intracardiac shunt resulting in an improved arterial saturation as well as immediate relief of patient's symptoms. This case illustrates the importance of suspecting and recognising POS clinically as well as the efficacy of transcatheter closure of PFO in such cases leading to resolution of hypoxaemia in a short span of time.
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Affiliation(s)
| | | | - Dhiraj Kumar
- Cardiology, KEM Hospital and Seth G S Medical College, Mumbai, India
| | - Charan Lanjewar
- Cardiology, KEM Hospital and Seth G S Medical College, Mumbai, India
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Han S, Dicker ML, Lopez-Ichikawa M, Vu NK, Rubinsky B, Chang TT. Irreversible Electroporation of the Liver Increases the Transplant Engraftment of Hepatocytes. J Surg Res 2024; 293:128-135. [PMID: 37738854 PMCID: PMC10999114 DOI: 10.1016/j.jss.2023.08.015] [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: 03/01/2023] [Revised: 07/25/2023] [Accepted: 08/23/2023] [Indexed: 09/24/2023]
Abstract
INTRODUCTION Irreversible electroporation (IRE) is a tissue ablation technology that kills cells with short electrical pulses that do not induce thermal damage, thereby preserving the extracellular matrix. Preclinical research suggests that IRE may be developed as a tool for regenerative surgery by clearing existing host cells within a solid organ and creating a supportive niche for new cell engraftment. We hypothesized that hepatocytes transplanted by injection into the portal circulation would preferentially engraft within liver parenchyma pretreated with IRE. METHODS Transgene-positive β-galactosidase-expressing hepatocytes were isolated from B6.129S7-Gt(ROSA)26Sor/J (ROSA26) mice and transplanted by intrasplenic injection into wild-type littermates that received liver IRE pretreatment or control sham treatment. Engraftment of donor hepatocytes in recipient livers was determined by X-gal staining. RESULTS Significantly higher numbers of X-gal+ donor hepatocytes engrafted in the livers of IRE-treated mice as compared to sham-treated mice. X-gal+ hepatocytes persisted in IRE-treated recipients for at least 11 d post-transplant and formed clusters. Immunostaining demonstrated the presence of HNF4A/Ki67/β-galactosidase triple-positive cells within IRE-ablation zones, indicating that transplanted hepatocytes preferentially engrafted in IRE-treated liver parenchyma and proliferated. CONCLUSIONS IRE pretreatment of the liver increased engraftment of transplanted hepatocytes within the IRE-ablation zone. IRE treatment of the host liver may be developed clinically as a strategy to increase engraftment efficiency of primary hepatocytes and/or hepatocytes derived from stem cells in cell transplant therapies.
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Affiliation(s)
- Simon Han
- Department of Surgery, University of California, San Francisco, California
| | - Marie L Dicker
- Department of Surgery, University of California, San Francisco, California
| | | | - Ngan K Vu
- Department of Surgery, University of California, San Francisco, California
| | - Boris Rubinsky
- Department of Mechanical Engineering, University of California, Berkeley, California
| | - Tammy T Chang
- Department of Surgery, University of California, San Francisco, California; Liver Center, University of California, San Francisco, California.
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Akdur A, Ayvazoğlu Soy HE, Karakaya E, Yıldırım S, Moray G, Haberal M. Living and Deceased Liver Donation Criteria of Baskent University. EXP CLIN TRANSPLANT 2022; 20:80-87. [DOI: 10.6002/ect.donorsymp.2022.o16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Zhang Y, Li B, He Q, Chu Z, Ji Q. Comparison of liver regeneration between donors and recipients after adult right lobe living-donor liver transplantation. Quant Imaging Med Surg 2022; 12:3184-3192. [PMID: 35655846 PMCID: PMC9131329 DOI: 10.21037/qims-21-1077] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 03/03/2022] [Indexed: 02/04/2025]
Abstract
BACKGROUND Living-donor liver transplantation (LDLT) is recognized as the standard treatment for end-stage liver diseases. The regeneration of the residual liver and graft after LDLT is important in evaluating surgical success. Previous studies have attempted to elucidate mechanisms, principles of liver regeneration after LDLT, or influencing factors. However, they have not ruled out patients with complications and reached a uniform conclusion. In this study, for the first time, we unified measurement methods of liver volumes and eliminated patients with complications to compare liver regeneration trends between donors and recipients after LDLT and search for potential influencing factors. METHODS A total of 61 donors and 62 recipients without complications after adult right lobe LDLT were included in this retrospective observational cohort study. The liver regeneration ratios (LRRs) at different time points in donors and recipients after LDLT were calculated and compared. Factors that affect LRRs include gender, age, graft with or without the middle hepatic vein (MHV), initial remnant liver (IRLV)/estimated standard liver volume (ESLV), initial graft volume (IGV)/ESLV, Child-Pugh grade, and model for end-stage liver disease (MELD) score of the recipients. Analysis of variance, independent-sample t-test, and correlation analysis were performed for statistical analyses. RESULTS Significant differences were found in LRRs between the donors and recipients after LDLT (all P<0.05). The LRRs of donors at 0.5, 1, 3, and 6 months were 80.80%±24.12% (72.87%, 88.73%), 98.62%±37.47% (75.97%, 121.26%), 103.34%±23.47% (83.73%, 122.96%), and 130.18%±17.68% (102.04%, 158.32%), respectively. The LRRs of recipients at 0.5, 1, 3, and 6 months were 58.49%±26.67% (49.04%, 67.95%), 50.16%±27.25% (40.94%, 59.38%), 44.36%±26.75% (35.30%, 53.41%), and 31.19%±22.57% (20.91%, 41.47%), respectively. The former values were higher than the latter. The LRRs of recipients with the MHV was higher than those without MHV at 1 and 3 months (P<0.05). The LRRs at 1 month were 59.63%±27.48% and 41.68%±24.73%, and at 3 months were 57.25%±25.42% and 32.81%±22.79%, respectively. The IRLV/ESLV and IGV/ESLV were negatively correlated with LRRs at several times [r=-0.419 (-0.646, -0.134), -0.608 (-0.832, -0.318), respectively; P<0.05]. At 0.5 month, significant difference was found between Child-Pugh score of ≤9.55 and >9.55 (P<0.05) and MELD score of ≤14 and >14 (P<0.05). CONCLUSIONS After LDLT, donors had more significant and faster liver regeneration than the recipients. Graft with or without MHV, initial liver volume, and preoperative liver function status of the recipients significantly affect liver regeneration.
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Affiliation(s)
- Yuling Zhang
- The First Central Clinical School, Tianjin Medical University, Nankai District, Tianjin, China
- Department of Radiology, Tianjin First Central Hospital, Nankai District, Tianjin, China
| | - Bei Li
- The First Central Clinical School, Tianjin Medical University, Nankai District, Tianjin, China
- Department of Radiology, Tianjin First Central Hospital, Nankai District, Tianjin, China
| | - Qing He
- The First Central Clinical School, Tianjin Medical University, Nankai District, Tianjin, China
- Department of Radiology, Tianjin First Central Hospital, Nankai District, Tianjin, China
| | - Zhiqiang Chu
- Department of Transplantation, Tianjin First Central Hospital, Nankai District, Tianjin, China
| | - Qian Ji
- Department of Radiology, Tianjin First Central Hospital, Nankai District, Tianjin, China
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García IC, Villalba JS, Iovino D, Franchi C, Iori V, Pettinato G, Inversini D, Amico F, Ietto G. Liver Trauma: Until When We Have to Delay Surgery? A Review. Life (Basel) 2022; 12:life12050694. [PMID: 35629360 PMCID: PMC9143295 DOI: 10.3390/life12050694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 04/06/2022] [Accepted: 04/29/2022] [Indexed: 01/09/2023] Open
Abstract
Liver involvement after abdominal blunt trauma must be expected, and in up to 30% of cases, spleen, kidney, and pancreas injuries may coexist. Whenever hemodynamics conditions do not contraindicate the overcoming of the ancient dogma according to which exploratory laparotomy should be performed after every major abdominal trauma, a CT scan has to clarify the liver lesions so as to determine the optimal management strategy. Except for complete vascular avulsion, no liver trauma grade precludes nonoperative management. Every attempt to treat the injured liver by avoiding a strong surgical approach may be considered. Each time, a nonoperative management (NOM) consisting of a basic “wait and see” attitude combined with systemic support and blood replacement are inadequate. Embolization should be considered to stop the bleeding. Percutaneous drainage of collections, endoscopic retrograde cholangiopancreatography (ERCP) with papilla sphincterotomy or stent placement and percutaneous transhepatic biliary drainage (PTBD) may avoid, or at least delay, surgical reconstruction or resection until systemic and hepatic inflammatory remodeling are resolved. The pathophysiological principle sustaining these leanings is based on the opportunity to limit the further release of cell debris fragments acting as damage-associated molecular patterns (DAMPs) and the following stress response associated with the consequent immune suppression after trauma. The main goal will be a faster recovery combined with limited cell death of the liver through the ischemic events that may directly follow the trauma, exacerbated by hemostatic procedures and surgery, in order to reduce the gross distortion of a regenerated liver.
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Affiliation(s)
- Inés Cañas García
- General and Digestive Surgery, Hospital Clínico San Cecilio of Granada, 18002 Granada, Spain;
| | - Julio Santoyo Villalba
- General and Digestive Surgery, Hospital Virgen de Las Nieves of Granada, 18002 Granada, Spain;
| | - Domenico Iovino
- General, Emergency and Transplant Surgery Department, ASST-Settelaghi and University of Insubria, 21100 Varese, Italy; (D.I.); (C.F.); (V.I.); (D.I.)
| | - Caterina Franchi
- General, Emergency and Transplant Surgery Department, ASST-Settelaghi and University of Insubria, 21100 Varese, Italy; (D.I.); (C.F.); (V.I.); (D.I.)
| | - Valentina Iori
- General, Emergency and Transplant Surgery Department, ASST-Settelaghi and University of Insubria, 21100 Varese, Italy; (D.I.); (C.F.); (V.I.); (D.I.)
| | - Giuseppe Pettinato
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA;
| | - Davide Inversini
- General, Emergency and Transplant Surgery Department, ASST-Settelaghi and University of Insubria, 21100 Varese, Italy; (D.I.); (C.F.); (V.I.); (D.I.)
| | - Francesco Amico
- Trauma Service, Department of Surgery, University of Newcastle, Newcastle 2308, Australia;
| | - Giuseppe Ietto
- General, Emergency and Transplant Surgery Department, ASST-Settelaghi and University of Insubria, 21100 Varese, Italy; (D.I.); (C.F.); (V.I.); (D.I.)
- Correspondence: ; Tel.: +39-339-8758024
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Azoulay D, Feray C, Lim C, Salloum C, Conticchio M, Cherqui D, Sa Cunha A, Adam R, Vibert E, Samuel D, Allard MA, Golse N. A systematic review of auxiliary liver transplantation of small for size grafts in patients with chronic liver disease. JHEP Rep 2022; 4:100447. [PMID: 35310820 PMCID: PMC8927838 DOI: 10.1016/j.jhepr.2022.100447] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/26/2022] [Accepted: 01/28/2022] [Indexed: 12/14/2022] Open
Abstract
Background & Aims The shortage of liver grafts continues to worsen. Because the expanded use of small-for-size grafts (SFSGs) would substantially alleviate this shortage, we aimed to analyse the available knowledge on auxiliary liver transplantation (ALT) with SFSGs in patients with chronic liver disease (CLD) to identify opportunities to develop ALT with SFSGs in patients with CLD. Methods This is a systematic review on ALT using SFSGs in patients with CLD. The review was completed by updates obtained from the authors of the retained reports. Results Heterotopic ALT was performed in 26 cases between 1980 and 2017, none for SFGS stricto sensu, and auxiliary partial orthotopic liver transplantation (APOLT) in 27 cases (from 1999 to 2021), all for SFSG. In APOLT cases, partial native liver resection was performed in most of cases, whereas the second-stage remnant native liver hepatectomy was performed in 9 cases only. The median graft-to-body weight ratio was 0.55, requiring perioperative or intraoperative portal modulation in 16 cases. At least 1 complication occurred in 24 patients following the transplant procedure (morbidity rate, 89%). Four patients (4/27, 15%) died after the APOLT procedure. At the long term, 19 (70%) patients were alive and well at 13 months to 24 years (median, 4.5 years) including 18 with the APOLT graft in place and 1 following retransplantation. Conclusions Despite high postoperative morbidity, and highly reported technical variability, the APOLT technique is a promising technique to use SFSGs in patients with CLD, achieving satisfactory long-term results. The results need to be confirmed on a larger scale, and a standardised technique could lead to even better results. Lay summary At the cost of a high postoperative morbidity, the long-term results of APOLT for small-for-size grafts are good. Standardisation of the procedure and of portal modulation remain needed.
Using a small-for-size graft is a risk factor of small-for-size syndrome. Auxiliary liver transplantation can be orthotopic or heterotopic. In auxiliary transplantation, the remnant native liver prevents small-for-size syndrome. Transplantation with a small-for-size graft requires individually tailored portal modulation. Auxiliary liver transplantation might substantially increase the number of available grafts.
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A modified animal model of hepatic regeneration induced by hilar bile duct ligation. Sci Rep 2021; 11:20201. [PMID: 34642435 PMCID: PMC8511257 DOI: 10.1038/s41598-021-99758-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Accepted: 09/24/2021] [Indexed: 11/08/2022] Open
Abstract
Mechanisms of the proliferation of liver are mainly studied in animal model of liver regeneration after partial hepatectomy (PH). However, the PH model involves complex regeneration mechanisms, including hemodynamic factors, cytokines, growth factors, and metabolites. Among liver metabolites, bile acid (BA) is a key signaling molecule that regulates liver regeneration. This study aimed to establish a new type of rapid liver hyperplasia model induced mainly by bile acid pathway through hepatoenteral circulation with hilar bile duct ligation (HBDL). We first established the HBDL model by ligating the bile duct of all hepatic lobes but the right lateral lobe in rabbits and compared with the PVL model and sham operation group. Changes in the liver lobe and hemodynamics were observed. Liver function and the bile acid level were also analyzed. Then we verified the HBDL model in mice. Liver function and the levels of bile acids and cytokines were tested. The protein and mRNA levels of FXR, FGF15, CYP7A1 and FoxM1b in liver tissue were also analyzed. After hilar ligation of the biliary tract, the unligated liver lobes proliferated significantly. Compared with those in the sham group, the volume and weight of the unligated right lateral lobe of the liver in the HBDL group and the PVL group increased significantly (P < 0.05). Transient liver function impairment occurred both in the HBDL group and PVL group in the rabbit model as well as the mouse models. The bile acid levels in the HBDL groups of the rabbit model and mouse model increased significantly within first week after surgery (P < 0.05). The immunohistochemistry results confirmed the proliferation of hepatocytes in the unligated liver lobe. Compared with those in the sham group, the levels of FXR, FGF15 and FoxM1b in the HBDL group were significantly increased (P < 0.05), while the expression of CYP7A1 was inhibited. Compared with those in the HBDL group, the postoperative hemodynamic changes in the PVL group were significant (P < 0.05). The levels of IL-6 and TNF-α in the HBDL group were higher than those in the sham group. The HBDL model is simple to establish and exhibits good surgical tolerance. The model has definite proliferative effect and strong specificity of bile acid pathway. This is an ideal animal model to study the mechanism of liver regeneration through bile acid pathway.
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Sonnenberg EM, Lee-Riddle GS, Walls DO, Caicedo JC, Jackson WE, Hughes L, Ladner DP, Liapakis A, Pomfret EA, Sarkar M, Selzner N, Torres AM, Abt PL, Olthoff KM. Pregnancy Outcomes After Living Liver Donation: A Multi-Institutional Study. Liver Transpl 2021; 27:1262-1272. [PMID: 33993632 DOI: 10.1002/lt.26098] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 04/07/2021] [Accepted: 05/03/2021] [Indexed: 01/13/2023]
Abstract
Nearly half of living liver donors in North America are women of child-bearing age. Fetal and maternal outcomes after donation are unknown. We conducted a retrospective cohort study of female living liver donors (aged 18-50 years at donation) from 6 transplant centers. Participants were surveyed about their pregnancies and fertility. Outcomes were compared between predonation and postdonation pregnancies. Generalized estimating equations were clustered on donor and adjusted for age at pregnancy, parity, and pregnancy year. Among the 276 donors surveyed, 151 donors responded (54.7% response rate) and reported 313 pregnancies; 168/199 (68.8%) of the predonation pregnancies and 82/114 (71.9%) of the postdonation pregnancies resulted in live births, whereas 16.6% and 24.6% resulted in miscarriage, respectively. Women with postdonation pregnancies were older (32.0 versus 26.7 years; P < 0.001) and more frequently reported abnormal liver enzymes during pregnancy (3.5% versus 0.0%; P = 0.02) and delivery via cesarean delivery (35.4% versus 19.7%; P = 0.01). On adjusted analysis, there was no difference in cesarean delivery (odds ratio [OR], 2.44; 95% confidence interval [95% CI], 0.98-6.08), miscarriage (OR, 1.59; 95% CI, 0.78-3.24), combined endpoints of pregnancy-induced hypertension and preeclampsia (OR, 1.27; 95% CI, 0.36-4.49), or intrauterine growth restriction and preterm birth (OR, 0.91; 95% CI, 0.19-4.3). Of the 49 women who attempted pregnancy after donation, 11 (22.5%) self-reported infertility; however, 8/11 (72.7%) eventually had live births. Aside from increased reporting of abnormal liver enzymes and cesarean deliveries, there was no significant difference in pregnancy outcomes before and after living liver donation. One-fifth of women who attempt pregnancy after liver donation reported infertility, and although the majority went on to successful live births, further exploration is needed to understand the contributing factors. Future research should continue to monitor this patient-centered outcome across a large cohort of donors.
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Affiliation(s)
| | - Grace S Lee-Riddle
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - David O Walls
- Department of Surgery, Robert Wood Johnson Medical School, New Brunswick, NJ
| | - Juan C Caicedo
- Comprehensive Transplant Center, Northwestern University Transplant Outcomes Research Collaborative, Feinberg School of Medicine, Northwestern University, Chicago, IL
| | - Whitney E Jackson
- Division of Gastroenterology and Hepatology, Department of Medicine, and the Colorado Center for Transplantation Care, Research and Education, University of Colorado, Aurora, CO
| | - Lisa Hughes
- Department of Medicine, Yale University, New Haven, CT
| | - Daniela P Ladner
- Comprehensive Transplant Center, Northwestern University Transplant Outcomes Research Collaborative, Feinberg School of Medicine, Northwestern University, Chicago, IL
| | | | - Elizabeth A Pomfret
- Department of Surgery and the Colorado Center for Transplantation Care, Research and Education, University of Colorado, Aurora, CO
| | - Monika Sarkar
- Department of Medicine, University of California San Francisco, San Francisco, CA
| | - Nazia Selzner
- Department of Medicine, Toronto General Hospital, Toronto, ON, Canada
| | - Ana Marie Torres
- Department of Medicine, University of California San Francisco, San Francisco, CA
| | - Peter L Abt
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Kim M Olthoff
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA
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12
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Kong L, Lv T, Yang J, Jiang L, Yang J. Adult split liver transplantation: A PRISMA-compliant Chinese single-center retrospective case-control study. Medicine (Baltimore) 2020; 99:e23750. [PMID: 33371134 PMCID: PMC7748205 DOI: 10.1097/md.0000000000023750] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Accepted: 11/17/2020] [Indexed: 02/05/2023] Open
Abstract
Although pediatric split liver transplantation (SLT) has been proven safe and the waitlist mortality rate has been successfully reduced, the safety of adult SLT has not been confirmed.Using 1:2 matching, 47 recipients who underwent adult SLT were matched to 94 of 743 recipients who underwent adult whole graft liver transplantation (WGLT). Eventually, 141 recipients were included in the case-control study. Subgroup analysis of 43 recipients in the SLT group was performed based on the presence of the middle hepatic vein (MHV) in the grafts.No significant differences in 5-year survival (80.8% vs 81.6%, P = .465) were observed between the adult SLT and WGLT groups. However, compared to recipients in the WGLT group, those in the SLT group had more Clavien-Dindo grade III-V complications, longer hospitalization duration, and higher mortality within 45 days. Furthermore, on multivariate analysis, 45-day postoperative mortality in recipients in the SLT group was mainly affected by hyperbilirubinemia within postoperative day (POD) 7-14, surgery time, and intraoperative blood loss. Subgroup analysis showed no significant differences in hyperbilirubinemia within POD 7-14, complications, and survival rate between SLTMHV(+) and SLTMHV [-].Adult SLT is safe and effective based on long-term survival rates; however, a reduction in the incidence of short-term complications is required. Non-obstructive hyperbilirubinemia within POD 7 to 14 is an independent predictor of short-term mortality after SLT.
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13
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Karakaya E, Akdur A, Ayvazoglu Soy EH, Harman A, Coskun M, Haberal M. Our Living Donor Protocol for Liver Transplant: A SingleCenter Experience. EXP CLIN TRANSPLANT 2020; 18:689-695. [PMID: 33187462 DOI: 10.6002/ect.2020.0280] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES The shortage of deceased donor organs is a limiting factor in transplant. The growing discrepancy between the wait list demand versus the supply of deceased donor organs has created an incentive for consideration of living donor liver transplant as an alternative. Here, we describe our evaluation process and donor complications. MATERIALS AND METHODS Since 1988, we have performed 659 (449 living donor and 210 deceased donor) liver transplants. The most important evaluation criteria is the relationship between donor and recipient, and we require thatthe donor must be related to the recipient. The evaluation protocol has 5 stages. Donor complications were defined as simple, moderate, and severe. RESULTS We retrospectively investigated data for 1387 candidates, and 938 (67.7%) were rejected; subsequently, 449 living donor liver transplants were performed. There were no complications in 398 of the donors (88.7%). Total complication rate was 11.3%. Simple complications were seen in 31 patients (6.9%). Moderate complications were seen in 19 patients (4.2%). We had only 1 severe complication, ie, organ failure from unspecified liver necrosis, which resulted in death. CONCLUSIONS The relationship between donor and recipient and donor safety should be the primary focus for living donor liver transplant. Donor selection should be made carefully to minimize complications and provide adequately functional grafts.
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Affiliation(s)
- Emre Karakaya
- From the Baskent University Faculty of Medicine, Department of General Surgery, Division of Transplantation, Ankara, Turkey
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Preoperative Alanine Aminotransferase and Remnant Liver Volume Predict Liver Regeneration After Live Donor Hepatectomy. J Gastrointest Surg 2020; 24:1818-1826. [PMID: 31388890 DOI: 10.1007/s11605-019-04332-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Accepted: 07/16/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND Regeneration of the remnant liver in early postoperative period determines the outcome in live liver donors (LLDs). The aim of the current study is to evaluate the factors that influence liver regeneration following live donor hepatectomy. METHODS Total liver volume (TLV), estimated graft volume (EGV), and remnant liver volume (RLV) were calculated preoperatively in a prospective study of 154 LLDs. Absolute and percentage growth of remnant liver (regeneration index) in donor was estimated at 7th postoperative day (POD) by computed tomography (CT) volumetric analysis. RESULTS One hundred eighteen donors underwent right hepatectomy (RH), 29 underwent left hepatectomy (LH), 6 donors had left lateral sectionectomy (LLS), and one had right posterior sectionectomy. The median percentage growth of remnant liver at the end of the first week was 46.14% (51.74%, 35.32%, and 17.38% for RH, LH, and LLS, respectively). On univariate analysis, female donors (p = 0.051), RH graft (p = 0.001), no steatosis on ultrasonography (p = 0.042), lower TLV (p = 0.029), RLV (p = < 0.001), RLV-to-body weight ratio (RLVBWR) (p = < 0.001), preoperative alanine aminotransferase (ALT) level (p = 0.017), aspartate aminotransferase (AST) (p = 0.035) and higher POD 7 alkaline phosphatase (ALP) (p = 0.033), and POD 7 gamma-glutamyl transferase GGT (p = 0.006) were found to be predictors of greater liver regeneration. Among them, lower RLV (P = 0.008), RLVBWR (p = 0.011), and preoperative ALT level (p = 0.021) were most significant factors predictive of liver regeneration on logistic regression analysis with backward elimination. CONCLUSION The liver regenerates rapidly in LLDs following hepatectomy. Low RLV, RLVBWR, and preoperative ALT levels were predictors of liver regeneration in the first week following donor hepatectomy.
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Truant S, Baillet C, Fulbert M, Olivier A, Sergent G, Turpin A, Boleslawski E, El Amrani M, Huglo D, Pruvot FR. Asymmetric kinetics of volume and function of the remnant liver after major hepatectomy as a key for postoperative outcome - A case-matched study. HPB (Oxford) 2020; 22:855-863. [PMID: 31669198 DOI: 10.1016/j.hpb.2019.10.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 08/22/2019] [Accepted: 10/01/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND The kinetics of remnant liver (RL) function is unknown after major hepatectomy (MH), especially in case of post-hepatectomy liver failure (PHLF). This study investigated the change in RL function after MH using 99mTc-labelled-mebrofenin SPECT-scintigraphy and its correlation with RL volume and PHLF. METHODS From 2011 to 2015, 125 patients undergoing MH had volumetric assessment by CT and functional SPECT-scintigraphy preoperatively and at day 7 (POD7) and 1 month (1M). RL volume and function changes were compared in (i) overall population and (ii) 17 patients with vs. 42 without PHLF (ISGLS) matched on preoperative RL function. RESULTS Increase in RL function correlated poorly with volume increase at POD7 (r = 0.035, p = 0.43) and 1M (r = 0.394, p < 0.0001). Overall, function increase on POD7 (+38.8%) was lower than volume (+49.4%), but comparable at 1M (+78.8% vs. +73%). PHLF patients showed lower function increase on POD7 (+2.1% [-89%-77.8%] vs. +50% [-39%-218%]; p = 0.006). At 1M, 4 PHLF patients died with no function increase despite significant volumetric gain. CONCLUSIONS We first showed via sequential SPECT-scintigraphy that RL function increase after MH is slower than volume increase. A poor kinetic of function was correlated with PHLF as early as POD7, contrasting with substantial volume gain in PHLF patients.
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Affiliation(s)
- Stéphanie Truant
- Department of Digestive Surgery and Transplantation, CHU, Univ Nord de France, F-59000 Lille, France.
| | - Clio Baillet
- Department of Nuclear Medicine, CHU, Univ Nord de France, F-59000 Lille, France
| | - Maxence Fulbert
- Department of Digestive Surgery and Transplantation, CHU, Univ Nord de France, F-59000 Lille, France
| | - Anais Olivier
- Department of Nuclear Medicine, CHU, Univ Nord de France, F-59000 Lille, France
| | - Géraldine Sergent
- Department of Radiology, CHU, Univ Nord de France, F-59000 Lille, France
| | - Anthony Turpin
- Department of Medical Oncology, CHU, Univ Nord de France, F-59000 Lille, France
| | - Emmanuel Boleslawski
- Department of Digestive Surgery and Transplantation, CHU, Univ Nord de France, F-59000 Lille, France
| | - Mehdi El Amrani
- Department of Digestive Surgery and Transplantation, CHU, Univ Nord de France, F-59000 Lille, France
| | - Damien Huglo
- Department of Nuclear Medicine, CHU, Univ Nord de France, F-59000 Lille, France
| | - François-René Pruvot
- Department of Digestive Surgery and Transplantation, CHU, Univ Nord de France, F-59000 Lille, France
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16
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Aierken Y, Kong LX, Li B, Liu XJ, Lu S, Yang JY. Liver fibrosis is a major risk factor for liver regeneration: A comparison between healthy and fibrotic liver. Medicine (Baltimore) 2020; 99:e20003. [PMID: 32481371 DOI: 10.1097/md.0000000000020003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Blood flow factors, such as congestion or ischemia after hepatectomy, have a significant impact on liver regeneration, but with the popularization of precise hepatectomy technology, segmental hepatectomy without congestion or ischemia has become the preferred treatment. Our aim is to investigate the factors affecting liver regeneration after hepatectomy without blood flow changes, and to provide clinical evidence for surgeons on the timing of second hepatectomy for cirrhosis patients with hepatocellular carcinoma (HCC). METHODS This study retrospectively analyzed data from patients who underwent right hepatectomy without middle hepatic vein (MHV) in West China Hospital between January 2016 and January 2018. Eighteen living-donors without MHV as normal group and 45 HCC patients, further classified into 3 subgroups based on the severity of fibrosis using the Scheure system. Demographic data, pre- and postoperative liver function indexes, and remnant liver volume (RLV) were retrospectively compared. We also analyzed the remnant liver regeneration rate (RLRR) post-operatively in each group. The significant indexes in univariate analysis were further analyzed using both receiver operating characteristic (ROC) analysis and multivariate regression analysis. RESULTS Liver regeneration occurred in both living-donor and HCC groups after hepatectomy; the RLRRs at 1 month were 59.46 ± 10.39% and 57.27 ± 4.77% (P = .509), respectively. Regeneration in the cirrhosis group occurred more slowly and less completely compared with that in other groups. The regeneration rate in the first 6 months showed rapid increase and the RLRR reached above 70% in cirrhosis group. Multivariate and ROC analyses revealed that Alb and the hepatic fibrosis grade in the early postoperative period were significant predictors of remnant liver regeneration. CONCLUSION The liver regenerated in all HCC patients; however, regeneration was significantly slower and less complete compared with the normal liver, especially in the patients with cirrhosis. Therefore, it can be concluded that the degree of liver fibrosis is a major predictor of liver regeneration. Furthermore, the optimal time for second resection in recurrent HCC patients with cirrhosis was 6 months after the first operation.
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Affiliation(s)
| | - Ling-Xiang Kong
- Department of Liver Surgery and Liver Transplantation Center
| | - Bo Li
- Department of Liver Surgery and Liver Transplantation Center
| | - Xi-Jiao Liu
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Su Lu
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Jia-Yin Yang
- Department of Liver Surgery and Liver Transplantation Center
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Ability of the post-operative ALBI grade to predict the outcomes of hepatocellular carcinoma after curative surgery. Sci Rep 2020; 10:7290. [PMID: 32350365 PMCID: PMC7190718 DOI: 10.1038/s41598-020-64354-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 04/15/2020] [Indexed: 02/08/2023] Open
Abstract
The albumin-bilirubin (ALBI) grade has been validated as a significant predictor for hepatocellular carcinoma (HCC). However, there is little information about the impact of postoperative ALBI grade in patients with HCC who are undergoing liver resection. We enrolled 525 HCC patients who received primary resection from April 2001 to March 2017. The impact of the pre- and post-operative ALBI grades on overall survival (OS) and recurrence-free survival (RFS) were analyzed by multivariate analysis. During the follow-up period (mean, 65 months), 253 (48.1%) patients experienced recurrence, and 85 (16.2%) patients died. Multivariate analysis revealed that diabetes mellitus (DM) (p = 0.011), alpha-fetoprotein levels (AFP) (p < 0.001), low platelet count (p = 0.008), liver cirrhosis (p < 0.001), and the first year of ALBI grade after resection (p < 0.001) were independent predictors for RFS. Additionally, old age (p = 0.006), DM (p = 0.002), AFP (p = 0.027), and ALBI grade at the first year after resection (p < 0.001) were independent risk factors for poor liver-related survival. Patients with post-operative ALBI grades II/III had older age (p = 0.019), hypoalbuminemia (p = 0.038), DM (p = 0.043), and high stages of pTNM (p = 0.021). The post-operative ALBI grade is better for predicting the outcomes in HCC patients after curative hepatectomy than the pre-operative ALBI grade.
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Hsieh CE, Lin KH, Hsu YL, Chou CT, Chen CB, Lin PY, Lin CC, Hung YJ, Weng LC, Chen YL. Clinical Outcome of Residual Liver Volume and Hepatic Steatosis After Right-Lobe Living-Donor Hepatectomy. Ann Transplant 2020; 25:e919502. [PMID: 32152262 PMCID: PMC7083085 DOI: 10.12659/aot.919502] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background We examine how residual liver volume (RLV) and hepatic steatosis (HS) of living liver donors affect the regeneration process and clinical outcomes. Material/Methods We longitudinally studied 58 donors who underwent right-lobe hepatectomy during the period February 2014 to February 2015 at a single medical institution. The patients were classified based on RLV (30–35%, 35–40%, 40–50%) subgroups and HS (<10%, 10–30%, 30–50%) subgroups. Clinical parameters such as clinical outcome, liver volumetric recovery (LVR,%) rate and remnant left-liver (RLL,%) growth rate were collected for analysis. Results The clinical features of postoperative peak total bilirubin (p=.024) were significant in the 3 RLV subgroups. Body mass index (p=.017), preoperative alanine transaminase (p<.001), and pleural effusion (p=.038) were significant in the 3 HS subgroups. The LVR rate and RLL growth rate equations showed significant variation in regeneration among the 3 RLV subgroups. The LVR rate and RLL growth rate equations did not show significant variation in regeneration among the 3 HS subgroups. Conclusions Hyperbilirubinemia was a risk factor in the small-RLV group, and a large amount of pleural effusion was a risk factor in the steatosis 30–50% group. Hepatic steatosis subgroups did not show significantly different degrees of regeneration. The safety of living donors was a major concern while we compiled the extended living-donor criteria presented in this paper.
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Affiliation(s)
- Chia-En Hsieh
- Department of Nursing, Changhua Christian Hospital, Changhua, Taiwan.,Graduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan
| | - Kuo-Hua Lin
- Department of General Surgery, Changhua Christian Hospital, Changhua, Taiwan
| | - Ya-Lan Hsu
- Department of Nursing, Changhua Christian Hospital, Changhua, Taiwan
| | - Chen-Te Chou
- Department of Radiology, Changhua Christian Hospital, Changhua, Taiwan.,Department of Biomedical Imaging and Radiological Science, National Yang-Ming Medical University, Taipei, Taiwan
| | - Chia-Bang Chen
- Department of Radiology, Changhua Christian Hospital, Changhua, Taiwan
| | - Ping-Yi Lin
- Transplant Medicine and Surgery Research Center, Changhua Christian Hospital, Changhua, Taiwan
| | - Chia-Cheng Lin
- Department of General Surgery, Changhua Christian Hospital, Changhua, Taiwan
| | - Yu-Ju Hung
- Department of General Surgery, Changhua Christian Hospital, Changhua, Taiwan
| | - Li-Chueh Weng
- Department of Nursing, Graduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan
| | - Yao-Li Chen
- Department of General Surgery, Changhua Christian Hospital, Changhua, Taiwan
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19
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Maeda T, Yokoyama Y, Ebata T, Igami T, Mizuno T, Yamaguchi J, Onoe S, Ando M, Nagino M. Discrepancy between volume and functional recovery in early phase liver regeneration following extended hepatectomy with extrahepatic bile duct resection. Hepatol Res 2019; 49:1227-1235. [PMID: 31117157 DOI: 10.1111/hepr.13378] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Revised: 04/30/2019] [Accepted: 05/13/2019] [Indexed: 02/08/2023]
Abstract
AIM To elucidate the clinical factors having an impact on liver regeneration rate following preoperative portal vein embolization (PVE) and subsequent extended hepatectomy. The correlation between liver volume and functional recovery after extended hepatectomy was also investigated. METHODS Records of patients who underwent extended hepatectomy with extrahepatic bile duct resection following PVE for perihilar cholangiocarcinoma were reviewed retrospectively with attention to liver regeneration. All patients underwent computed tomography before PVE, after PVE (immediately before surgery), and on postoperative day (POD) 7. The kinetic growth rate (KGR) was calculated as the percent increase in liver volume relative to the future liver remnant volume per day after PVE (KGRPVE ) and after POD 7 (KGRPOD7 ) using the computed tomography images before PVE, after PVE, and on POD 7. RESULTS In the 289 study patients, the median of KGRPVE was 1.35%/day whereas that of KGRPOD7 was 5.56%/day. The extent of liver resection had the greatest impact on both KGRPVE and KGRPOD7 and the impacts of other factors were less. There was a significant negative correlation between KGRPVE and KGRPOD7 (P = 0.002). No correlations were observed between KGRPVE or KGRPOD7 and serum total bilirubin and prothrombin time - international normalized ratio on POD 7, nor in the incidence of liver failure after surgery. CONCLUSIONS Early phase liver regeneration after extended hepatectomy was largely influenced by the extent of liver resection and showed no correlation with the indices of liver failure. There was a discrepancy between volume and functional recovery in early phase liver regeneration.
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Affiliation(s)
- Takashi Maeda
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine
| | - Yukihiro Yokoyama
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine
| | - Tomoki Ebata
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine
| | - Tsuyoshi Igami
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine
| | - Takashi Mizuno
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine
| | - Junpei Yamaguchi
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine
| | - Shunsuke Onoe
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine
| | - Masahiko Ando
- Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan
| | - Masato Nagino
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine
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Gong WF, Zhong JH, Lu Z, Zhang QM, Zhang ZY, Chen CZ, Liu X, Ma L, Zhang ZM, Xiang BD, Li LQ. Evaluation of liver regeneration and post-hepatectomy liver failure after hemihepatectomy in patients with hepatocellular carcinoma. Biosci Rep 2019; 39:BSR20190088. [PMID: 31383787 PMCID: PMC6706596 DOI: 10.1042/bsr20190088] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 07/03/2019] [Accepted: 07/30/2019] [Indexed: 02/06/2023] Open
Abstract
Aim: To explore clinical factors associated with extent of liver regeneration after hemihepatectomy to treat hepatocellular carcinoma (HCC).Methods: Future liver remnant volume (as a percentage of functional liver volume, %FLRV) and remnant liver volume were measured preoperatively and at 1, 5, 9, and 13 weeks postoperatively.Results: After hepatectomy, 1 of 125 patients (0.8%) died within 3 months, 13 (10.4%) experienced liver failure, and 99 (79.2%) experienced complications. %FLRV was able to predict liver failure with an area under the receiver operating characteristic curve of 0.900, and a cut-off value of 42.7% showed sensitivity of 85.7% and specificity of 88.6%. Postoperative median growth ratio was 21.3% at 1 week, 30.9% at 5 weeks, 34.6% at 9 weeks, and 37.1% at 13 weeks. Multivariate analysis identified three predictors associated with liver regeneration: FLRV < 601 cm3, %FLRV, and liver cirrhosis. At postoperative weeks (POWs) 1 and 5, liver function indicators were significantly better among patients showing high extent of regeneration than among those showing low extent, but these differences disappeared by POW 9.Conclusions: FLRV, %FLRV, and liver cirrhosis strongly influence extent of liver regeneration after hepatectomy. %FLRV values below 42.7% are associated with greater risk of post-hepatectomy liver failure.
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Affiliation(s)
- Wen-Feng Gong
- Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China
| | - Jian-Hong Zhong
- Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China
| | - Zhan Lu
- Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Qiu-Ming Zhang
- General Medicine Department, The First People's Hospital of Qinzhou, Qinzhou, China
| | - Zhi-Yuan Zhang
- Hepatobiliary Surgery Department, The Fifth Affiliated Hospital of Guangxi Medical University, Guigang, China
| | - Chang-Zhi Chen
- Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Xu Liu
- Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Liang Ma
- Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China
| | - Zhi-Ming Zhang
- Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China
| | - Bang-De Xiang
- Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China
| | - Le-Qun Li
- Hepatobiliary Surgery Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China
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Kim YH, Park UJ, Chung HS, Hong SH, Park CS, Choi JH, Choi HJ, Jung JY, Chae MS. Recovery of the Psoas Muscle Index in Living Donors after a Right Lobe Hepatectomy for Liver Transplantation: A Single-Center Experience. Transplant Proc 2019; 51:1853-1860. [PMID: 31256871 DOI: 10.1016/j.transproceed.2019.04.027] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Revised: 04/15/2019] [Accepted: 04/22/2019] [Indexed: 12/18/2022]
Abstract
OBJECTIVE The development of sarcopenia leads to adverse postoperative outcomes. However, no study has investigated perioperative loss in core muscle and the correlation between core muscle and residual liver volume in living donors for liver transplant. PATIENTS AND METHODS A total of 457 adult healthy donors who underwent a right lobe hepatectomy without the middle hepatic vein for elective liver transplant were retrospectively analyzed. Abdominal computed tomography was performed within 1 month before surgery and the first week and 3 months after the surgery. The average psoas muscle area between lumbar vertebrae 3 and 4 was measured and normalized by height squared (psoas muscle index [PMI] = psoas muscle area/height2). The initial whole liver volume and remnant left lobe volume were measured on computed tomography images. RESULTS The study cohort included 279 men (61.1%) and 178 women (38.9%). The median preoperative PMIs were 420.9 mm2/m2 (interquartile range, 360.6-487.0 mm2/m2) in men and 280.9 mm2/m2 (interquartile range, 243.5-318.7 mm2/m2) in women. The PMIs in men and women significantly decreased during the first week after surgery, and gradually recovered to preoperative levels during the first 3 months after surgery. Based on the ratio between the remnant left lobe and initial whole liver volume (≥30%), the increase in remnant left lobe volume was not correlated with the decrease in PMI on postoperative day 7. A postoperative U-shaped recovery in the core muscles was present in both male and female donors, independent of the remnant liver ratio. CONCLUSIONS Despite the requirements of partial liver regeneration and surgical wound repair, healthy donors did not suffer from sustained core muscle loss after surgery.
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Affiliation(s)
- Young Hye Kim
- Department of Anesthesiology and Pain Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ui Jin Park
- Department of Anesthesiology and Pain Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hyun Sik Chung
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sang Hyun Hong
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Chul Soo Park
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jong Ho Choi
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ho Joong Choi
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Joon-Yong Jung
- Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Min Suk Chae
- Department of Anesthesiology and Pain Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
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22
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Li M, Chu Z, Tan Z, Jin Y, Xu M, Ji Q. Impact of donor age on liver regeneration and function following adult living donor liver transplantation. Exp Ther Med 2019; 17:3965-3970. [PMID: 31007739 DOI: 10.3892/etm.2019.7454] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Accepted: 02/28/2019] [Indexed: 12/27/2022] Open
Abstract
The aim of the present study was to evaluate the impact of donor age on liver function and regeneration following living donor liver transplantation. Donors were divided into an elderly donor group (age >50 years old; n=8) and a young donor group (age <30 years old; n=35). The recipients were also divided into an elderly group (age >50 years old; n=5) and a young group (age <30 years old; n=25). Alanine aminotransferase, aspartate aminotransferase, total bilirubin (TB) and prothrombin time were recorded 1-5 days postoperatively. The liver regeneration ratio (LRR) was recorded 7 and 15 days postoperatively in donors and at 0.5, 1, 3 and 6 months postoperatively in recipients by contrast-enhanced multi-slice spiral computed tomography. Notably, the LRR in the young donor group was significantly increased compared with that in the elderly donor group at 7 days postoperatively (P<0.05). Among recipients, TB in the elderly group was significantly increased compared with that in the young group at 1-5 days postoperatively (P<0.05). The residual liver regeneration rate was decreased and the time of jaundice was prolonged in recipients in the elderly group 7 days postoperatively, but donor age had little impact on the short-term outcome of the residual liver and graft.
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Affiliation(s)
- Mingyang Li
- First Central Clinical College of Tianjin Medical University, Tianjin 300192, P.R. China
| | - Zhiqiang Chu
- Transplantation Center, Tianjin First Center Hospital, Tianjin 300192, P.R. China
| | - Zhijun Tan
- Department of General Surgery, Tianjin First Center Hospital, Tianjin 300192, P.R. China
| | - Yanyu Jin
- Department of General Surgery, Tianjin First Center Hospital, Tianjin 300192, P.R. China
| | - Min Xu
- First Central Clinical College of Tianjin Medical University, Tianjin 300192, P.R. China
| | - Qian Ji
- Department of Radiology, Tianjin First Center Hospital, Tianjin 300192, P.R. China
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23
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Soin AS, Chaudhary RJ, Pahari H, Pomfret EA. A Worldwide Survey of Live Liver Donor Selection Policies at 24 Centers With a Combined Experience of 19 009 Adult Living Donor Liver Transplants. Transplantation 2019; 103:e39-e47. [PMID: 30308575 DOI: 10.1097/tp.0000000000002475] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Although surgical technique in living donor liver transplantation (LDLT) has evolved with a focus on donor safety and recipient challenges, the donor selection criteria remain considerably disparate. METHODS A questionnaire on donor selection was sent to 41 centers worldwide. 24 centers with a combined experience of 19 009 LDLTs responded. RESULTS Centers were categorized into predominantly LDLT (18) or deceased donor liver transplantation (6), and high- (10) or low-volume (14) centers. At most centers, the minimum acceptable graft-to-recipient weight ratio was 0.7 or less (67%), and remnant was 30% (75%). The median upper limit of donor age was 60 years and body mass index of 33 kg/m. At 63% centers, age influenced the upper limit of body mass index inversely. Majority preferred aspartate transaminase and alanine transaminase less than 50 IU/mL. Most accepted donors with nondebilitating mild mental or physical disability and rejected donors with treated coronary artery disease, cerebrovascular accident and nonbrain, nonskin primary malignancies. Opinions were divided about previous psychiatric illness, substance abuse and abdominal surgery. Most performed selective liver biopsy, commonly for steatosis, raised transaminases and 1 or more features of metabolic syndrome. On biopsy, all considered macrovesicular and 50% considered microvesicular steatosis important. Nearly all (92%) rejected donors for early fibrosis, and minority for nonspecific granuloma or mild inflammation. Most anatomical anomalies except portal vein type D/E were acceptable at high-volume centers. There was no standard policy for preoperative or peroperative cholangiogram. CONCLUSIONS This first large live liver donor survey provides insight into donor selection practices that may aid standardization between centers, with potential expansion of the donor pool without compromising safety.
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Affiliation(s)
| | | | - Hirak Pahari
- Medanta Institute of Liver Transplantation, Haryana, India
| | - Elizabeth A Pomfret
- Division of Transplantation, University of Colorado Anschutz Medical Campus, Aurora, CO
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24
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Abu-Gazala S, Olthoff KM. Current Status of Living Donor Liver Transplantation in the United States. Annu Rev Med 2019; 70:225-238. [DOI: 10.1146/annurev-med-051517-125454] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Adult-to-adult living donor liver transplantation (LDLT) was introduced in response to the shortage of deceased donor liver grafts. The number of adult living donor transplants is increasing due to improved outcomes and increasing need. Advantages of LDLT include optimization of the timing of transplant, better organ quality, and lower rates of recipient mortality compared to staying on the wait list for deceased donor liver transplant. Donor safety remains the major focus when considering LDLT. Recent advancements have supported the increased use of LDLT to help decrease wait list death and improve long-term survival of transplant recipients.
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Affiliation(s)
- Samir Abu-Gazala
- Transplantation Unit, Department of Surgery, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel
| | - Kim M. Olthoff
- Division of Transplant Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-4283, USA
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25
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Yasuda S, Nomi T, Hokuto D, Yoshikawa T, Matsuo Y, Sho M. Liver Regeneration After Major Liver Resection for Hepatocellular Carcinoma in the Elderly. J INVEST SURG 2018; 33:332-338. [PMID: 30388925 DOI: 10.1080/08941939.2018.1517839] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Background: With an aging population, more elderly patients are being considered for hepatic resection for hepatocellular carcinoma (HCC). This study aimed to evaluate postoperative outcomes including liver regeneration after major hepatectomy for HCC in the elderly.Methods: We assessed 41 patients who underwent major hepatectomy (≥3 segments) at our institute between 2000 and 2013. Patients were divided into two age groups, elderly group (age ≥70 years, n = 23) and younger group (age <70 years, n = 18). Clinicopathological data and outcomes were retrospectively compared. To evaluate the effect of aging on liver regeneration, we measured liver volumes preoperatively and at 1 and 6 months after liver resection using a 3D simulation imaging system.Results: Overall and major complications after hepatectomy were not different between elderly and younger groups, and no case of mortality was recorded. Moreover, recurrence-free and overall survivals were similar in both groups. With regard to liver regeneration, no differences were observed between elderly and younger groups at 1 and 6 months after liver resection. Baseline liver functions were comparable between the groups. Furthermore, the only factor associated with liver regeneration was resected liver volume (R2 = 0.631, p < 0.001). Age was not correlated with liver regeneration rate (R2 = 0.00537, p = 0.695).Conclusions: Liver regeneration after major hepatectomy for HCC was not affected by age and that resected liver volume is an important factor for liver regeneration. Short- and long-term outcomes after major hepatectomy were similar in elderly and younger patients.
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Affiliation(s)
- Satoshi Yasuda
- Department of Surgery, Nara Medical University, 840 Shijo-cho Kashihara-shi, Nara 634-8522, Japan
| | - Takeo Nomi
- Department of Surgery, Nara Medical University, 840 Shijo-cho Kashihara-shi, Nara 634-8522, Japan
| | - Daisuke Hokuto
- Department of Surgery, Nara Medical University, 840 Shijo-cho Kashihara-shi, Nara 634-8522, Japan
| | - Takahiro Yoshikawa
- Department of Surgery, Nara Medical University, 840 Shijo-cho Kashihara-shi, Nara 634-8522, Japan
| | - Yasuko Matsuo
- Department of Surgery, Nara Medical University, 840 Shijo-cho Kashihara-shi, Nara 634-8522, Japan
| | - Masayuki Sho
- Department of Surgery, Nara Medical University, 840 Shijo-cho Kashihara-shi, Nara 634-8522, Japan
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26
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Hou CT, Chen YL, Lin CC, Chou CT, Lin KH, Lin PY, Hsu YL, Chen CB, Lin HC, Ko CJ, Wang SH, Weng LC, Hsieh CE. Portal venous velocity affects liver regeneration after right lobe living donor hepatectomy. PLoS One 2018; 13:e0204163. [PMID: 30222781 PMCID: PMC6141071 DOI: 10.1371/journal.pone.0204163] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Accepted: 09/03/2018] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVES We investigated whether chronological changes in portal flow and clinical factors play a role in the liver regeneration (LR) process after right donor-hepatectomy. MATERIALS AND METHODS Participants in this prospective study comprised 58 donors who underwent right donor-hepatectomy during the period February 2014 to February 2015 at a single medical institution. LR was estimated using two equations: remnant left liver (RLL) growth (%) and liver volumetric recovery (LVR) (%). Donors were classified into an excellent regeneration (ER) group or a moderate regeneration (MR) group based on how their LR on postoperative day 7 compared to the median value. RESULTS Multivariate analysis revealed that low residual liver volume (OR = .569, 95% CI: .367- .882) and high portal venous velocity in the immediate postoperative period (OR = 1.220, 95% CI: 1.001-1.488) were significant predictors of LR using the RLL growth equation; high portal venous velocity in the immediate postoperative period (OR = 1.325, 95% CI: 1.081-1.622) was a significant predictor of LR using the LVR equation. Based on the two equations, long-term LR was significantly greater in the ER group than in the MR group (p < .001). CONCLUSION Portal venous velocity in the immediate postoperative period was an important factor in LR. The critical time for short-term LR is postoperative day 7; it is associated with long-term LR in donor-hepatectomy.
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Affiliation(s)
- Chen-Tai Hou
- Surgical Critical Unit, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan
| | - Yao-Li Chen
- Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan
- School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- * E-mail: (CEH); (YLC)
| | - Chia-Cheng Lin
- Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan
| | - Chen-Te Chou
- Department of Radiology, Changhua Christian Hospital, Changhua, Taiwan
- Department of Biomedical Imaging and Radiological Science, National Yang-Ming Medical University, Taiper, Taiwan
| | - Kuo-Hua Lin
- Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan
| | - Ping-Yi Lin
- Transplant Medicine & Surgery Research Centre, Changhua Christian Hospital, Changhua, Taiwan
| | - Ya-Lan Hsu
- Department of Nursing, Changhua Christian Hospital, Changhua, Taiwan
| | - Chia-Bang Chen
- Department of Radiology, Changhua Christian Hospital, Changhua, Taiwan
| | - Hui-Chuan Lin
- Department of Nursing, Hung Kuang University, Taichung, Taiwan
| | - Chih-Jan Ko
- Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan
| | - Su-Han Wang
- Department of Nursing, Changhua Christian Hospital, Changhua, Taiwan
| | - Li-Chueh Weng
- Department of Nursing, Graduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan
| | - Chia-En Hsieh
- Department of Nursing, Changhua Christian Hospital, Changhua, Taiwan
- Graduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan
- * E-mail: (CEH); (YLC)
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27
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Abu-Gazala S, Olthoff KM. Status of Adult Living Donor Liver Transplantation in the United States: Results from the Adult-To-Adult Living Donor Liver Transplantation Cohort Study. Gastroenterol Clin North Am 2018; 47:297-311. [PMID: 29735025 DOI: 10.1016/j.gtc.2018.01.004] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/16/2023]
Abstract
This article reviews the Adult-to-Adult Living Donor Liver Transplant Cohort Study (A2ALL). The findings show that the number of adult-to-adult living donor liver transplants is consistently increasing. Living donor liver transplantation has an important benefit for patients with acute liver failure, does not compromise donor safety, and has lower rates of acute cellular rejection in biologically related donor and recipient. The conclusions from the A2ALL consortium have been critical in transplant advancement, supporting increased use to help decrease waitlist death and improve long-term survival of transplant recipients.
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Affiliation(s)
- Samir Abu-Gazala
- Department of Surgery, Transplantation Unit, Hadassah Hebrew University Medical Center, Kiryat Hadassah, POB 12000, Jerusalem 91120, Israel.
| | - Kim M Olthoff
- Department of Surgery, Division of Transplant Surgery, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
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28
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Aston PJ. A New Model for the Dynamics of Hepatitis C Infection: Derivation, Analysis and Implications. Viruses 2018; 10:v10040195. [PMID: 29652855 PMCID: PMC5923489 DOI: 10.3390/v10040195] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Revised: 03/29/2018] [Accepted: 04/10/2018] [Indexed: 02/07/2023] Open
Abstract
We review various existing models of hepatitis C virus (HCV) infection and show that there are inconsistencies between the models and known behaviour of the infection. A new model for HCV infection is proposed, based on various dynamical processes that occur during the infection that are described in the literature. This new model is analysed, and three steady state branches of solutions are found when there is no stem cell generation of hepatocytes. Unusually, the branch of infected solutions that connects the uninfected branch and the pure infection branch can be found analytically and always includes a limit point, subject to a few conditions on the parameters. When the action of stem cells is included, the bifurcation between the pure infection and infected branches unfolds, leaving a single branch of infected solutions. It is shown that this model can generate various viral load profiles that have been described in the literature, which is confirmed by fitting the model to four viral load datasets. Suggestions for possible changes in treatment are made based on the model.
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Affiliation(s)
- Philip J Aston
- Department of Mathematics, University of Surrey, Guildford, Surrey GU2 7XH, UK.
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29
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Sable SA, Maheshwari S, Sharma S, Yadav K, Chauhan A, Kapoor S, Varma V, Kumaran V. Kinetics of liver regeneration in donors after living donor liver transplantation: A retrospective analysis of "2/3rd partial hepatectomy" model at 3 months. Indian J Gastroenterol 2018; 37:133-140. [PMID: 29594724 DOI: 10.1007/s12664-018-0838-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Accepted: 03/01/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND/AIM Right lobe living donor (2/3rd partial hepatectomy) model is the best way to accurately study liver regeneration process in human beings. We aimed to study the kinetics of liver regeneration after 2/3rd partial hepatectomy in donors. METHODS Retrospective analysis of prospectively maintained volumetric recovery data in donors was performed in 23 donors, who underwent 29 contrast-enhanced computed tomography within 3 months for various clinical indications. RESULTS The absolute volumetric growth percentages were as follows: 37.60 ± 21.74 at 1st week, 92 ± 53.27 at 2nd week, 115.55 ± 59.65 at 4th week, and 110.79 ± 64.47 at 3 months. On sub-group analysis of our cohort, we found that 4.3%, 17%, 30.4%, and 39% donors attended ≥ 90% volumetric recovery at 1st, 2nd, 4th week, and 3 months, respectively. One patient at 4th week revealed 128% volumetric recovery. There was one more patient who exceeded original total liver volumes (TLV) (111% of TLV) at 2.5 months. The serum bilirubin and INR values peaked at postoperative day (POD) 3rd and then started showing a downward trend from POD 5th onwards. CONCLUSION Our study is the first to document complete volumetric recovery in donors as early as 3 weeks. Two of the donors overshot their original TLV during the early regenerative phase.
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Affiliation(s)
- Shailesh Anand Sable
- Department of Liver Transplantation and HPB Surgery, Kokilaben Dhirubhai Ambani Hospital, Mumbai, 400 053, India.
| | - Sharad Maheshwari
- Department of Radio-Diagnosis, Kokilaben Dhirubhai Ambani Hospital, Mumbai, 400 053, India
| | - Swapnil Sharma
- Department of Liver Transplantation and HPB Surgery, Kokilaben Dhirubhai Ambani Hospital, Mumbai, 400 053, India
| | - Kapildev Yadav
- Department of Liver Transplantation and HPB Surgery, Kokilaben Dhirubhai Ambani Hospital, Mumbai, 400 053, India
| | - Ashutosh Chauhan
- Department of Liver Transplantation and HPB Surgery, Kokilaben Dhirubhai Ambani Hospital, Mumbai, 400 053, India
| | - Sorabh Kapoor
- Department of Liver Transplantation and HPB Surgery, Kokilaben Dhirubhai Ambani Hospital, Mumbai, 400 053, India
| | - Vibha Varma
- Department of Liver Transplantation and HPB Surgery, Kokilaben Dhirubhai Ambani Hospital, Mumbai, 400 053, India
| | - Vinay Kumaran
- Department of Liver Transplantation and HPB Surgery, Kokilaben Dhirubhai Ambani Hospital, Mumbai, 400 053, India
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30
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Jung KW, Kim WJ, Jeong HW, Kwon HM, Moon YJ, Jun IG, Song JG, Hwang GS. Impact of Inhalational Anesthetics on Liver Regeneration After Living Donor Hepatectomy. Anesth Analg 2018; 126:796-804. [DOI: 10.1213/ane.0000000000002756] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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31
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Alvarez-Sola G, Uriarte I, Latasa MU, Jimenez M, Barcena-Varela M, Santamaría E, Urtasun R, Rodriguez-Ortigosa C, Prieto J, Corrales FJ, Baulies A, García-Ruiz C, Fernandez-Checa JC, Berraondo P, Fernandez-Barrena MG, Berasain C, Avila MA. Engineered fibroblast growth factor 19 protects from acetaminophen-induced liver injury and stimulates aged liver regeneration in mice. Cell Death Dis 2017; 8:e3083. [PMID: 28981086 PMCID: PMC5682649 DOI: 10.1038/cddis.2017.480] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Revised: 07/31/2017] [Accepted: 08/09/2017] [Indexed: 02/07/2023]
Abstract
The liver displays a remarkable regenerative capacity triggered upon tissue injury or resection. However, liver regeneration can be overwhelmed by excessive parenchymal destruction or diminished by pre-existing conditions hampering repair. Fibroblast growth factor 19 (FGF19, rodent FGF15) is an enterokine that regulates liver bile acid and lipid metabolism, and stimulates hepatocellular protein synthesis and proliferation. FGF19/15 is also important for liver regeneration after partial hepatectomy (PH). Therefore recombinant FGF19 would be an ideal molecule to stimulate liver regeneration, but its applicability may be curtailed by its short half-life. We developed a chimaeric molecule termed Fibapo in which FGF19 is covalently coupled to apolipoprotein A-I. Fibapo retains FGF19 biological activities but has significantly increased half-life and hepatotropism. Here we evaluated the pro-regenerative activity of Fibapo in two clinically relevant models where liver regeneration may be impaired: acetaminophen (APAP) poisoning, and PH in aged mice. The only approved therapy for APAP intoxication is N-acetylcysteine (NAC) and no drugs are available to stimulate liver regeneration. We demonstrate that Fibapo reduced liver injury and boosted regeneration in APAP-intoxicated mice. Fibapo improved survival of APAP-poisoned mice when given at later time points, when NAC is ineffective. Mechanistically, Fibapo accelerated recovery of hepatic glutathione levels, potentiated cell growth-related pathways and increased functional liver mass. When Fibapo was administered to old mice prior to PH, liver regeneration was markedly increased. The exacerbated injury developing in these mice upon PH was attenuated, and the hepatic biosynthetic capacity was enhanced. Fibapo reversed metabolic and molecular alterations that impede regeneration in aged livers. It reduced liver steatosis and downregulated p21 and hepatocyte nuclear factor 4 α (Hnf4α) levels, whereas it stimulated Foxm1b gene expression. Together our findings indicate that FGF19 variants retaining the metabolic and growth-promoting effects of this enterokine may be valuable for the stimulation of liver regeneration.
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Affiliation(s)
- Gloria Alvarez-Sola
- CIBERehd, Instituto de Salud Carlos III, Clinica Universidad de Navarra, Avda, Pio XII, n 36, Pamplona 31008, Spain
| | - Iker Uriarte
- CIBERehd, Instituto de Salud Carlos III, Clinica Universidad de Navarra, Avda, Pio XII, n 36, Pamplona 31008, Spain
| | - Maria U Latasa
- Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, Pamplona 31008, Spain
| | - Maddalen Jimenez
- Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, Pamplona 31008, Spain
| | - Marina Barcena-Varela
- Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, Pamplona 31008, Spain
| | - Eva Santamaría
- CIBERehd, Instituto de Salud Carlos III, Clinica Universidad de Navarra, Avda, Pio XII, n 36, Pamplona 31008, Spain
| | - Raquel Urtasun
- Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, Pamplona 31008, Spain
| | - Carlos Rodriguez-Ortigosa
- CIBERehd, Instituto de Salud Carlos III, Clinica Universidad de Navarra, Avda, Pio XII, n 36, Pamplona 31008, Spain
- Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, Pamplona 31008, Spain
| | - Jesús Prieto
- CIBERehd, Instituto de Salud Carlos III, Clinica Universidad de Navarra, Avda, Pio XII, n 36, Pamplona 31008, Spain
- Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, Pamplona 31008, Spain
| | - Fernando J Corrales
- Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, Pamplona 31008, Spain
- CIBERehd, Instituto de Salud Carlos III, Barcelona, Spain
| | - Anna Baulies
- CIBERehd, Instituto de Salud Carlos III, Barcelona, Spain
- Department of Cell Death and Proliferation, Instituto de Investigaciones Biomédicas de Barcelona, CSIC and Liver Unit-Hospital Clinic-IDIBAPS, Barcelona, Spain
- Research Center for ALPD, Keck School of Medicine, University of Southern California, Los Angeles 90033, CA, USA
| | - Carmen García-Ruiz
- CIBERehd, Instituto de Salud Carlos III, Barcelona, Spain
- Department of Cell Death and Proliferation, Instituto de Investigaciones Biomédicas de Barcelona, CSIC and Liver Unit-Hospital Clinic-IDIBAPS, Barcelona, Spain
- Research Center for ALPD, Keck School of Medicine, University of Southern California, Los Angeles 90033, CA, USA
| | - Jose C Fernandez-Checa
- CIBERehd, Instituto de Salud Carlos III, Barcelona, Spain
- Department of Cell Death and Proliferation, Instituto de Investigaciones Biomédicas de Barcelona, CSIC and Liver Unit-Hospital Clinic-IDIBAPS, Barcelona, Spain
- Research Center for ALPD, Keck School of Medicine, University of Southern California, Los Angeles 90033, CA, USA
| | - Pedro Berraondo
- Immunology and Immunotherapy Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, Pamplona 31008, Spain
| | - Maite G Fernandez-Barrena
- CIBERehd, Instituto de Salud Carlos III, Clinica Universidad de Navarra, Avda, Pio XII, n 36, Pamplona 31008, Spain
- Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, Pamplona 31008, Spain
| | - Carmen Berasain
- CIBERehd, Instituto de Salud Carlos III, Clinica Universidad de Navarra, Avda, Pio XII, n 36, Pamplona 31008, Spain
- Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, Pamplona 31008, Spain
| | - Matías A Avila
- CIBERehd, Instituto de Salud Carlos III, Clinica Universidad de Navarra, Avda, Pio XII, n 36, Pamplona 31008, Spain
- Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, Pamplona 31008, Spain
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Alvarez-Sola G, Uriarte I, Latasa MU, Jimenez M, Barcena-Varela M, Santamaría E, Urtasun R, Rodriguez-Ortigosa C, Prieto J, Berraondo P, Fernandez-Barrena MG, Berasain C, Avila MA. Bile acids, FGF15/19 and liver regeneration: From mechanisms to clinical applications. Biochim Biophys Acta Mol Basis Dis 2017; 1864:1326-1334. [PMID: 28709961 DOI: 10.1016/j.bbadis.2017.06.025] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Revised: 06/22/2017] [Accepted: 06/26/2017] [Indexed: 12/12/2022]
Abstract
The liver has an extraordinary regenerative capacity rapidly triggered upon injury or resection. This response is intrinsically adjusted in its initiation and termination, a property termed the "hepatostat". Several molecules have been involved in liver regeneration, and among them bile acids may play a central role. Intrahepatic levels of bile acids rapidly increase after resection. Through the activation of farnesoid X receptor (FXR), bile acids regulate their hepatic metabolism and also promote hepatocellular proliferation. FXR is also expressed in enterocytes, where bile acids stimulate the expression of fibroblast growth factor 15/19 (FGF15/19), which is released to the portal blood. Through the activation of FGFR4 on hepatocytes FGF15/19 regulates bile acids synthesis and finely tunes liver regeneration as part of the "hepatostat". Here we review the experimental evidences supporting the relevance of the FXR-FGF15/19-FGFR4 axis in liver regeneration and discuss potential therapeutic applications of FGF15/19 in the prevention of liver failure. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.
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Affiliation(s)
- Gloria Alvarez-Sola
- CIBERehd, Instituto de Salud Carlos III, Clinica Universidad de Navarra, Avda. Pio XII, n 36, 31008 Pamplona, Spain
| | - Iker Uriarte
- CIBERehd, Instituto de Salud Carlos III, Clinica Universidad de Navarra, Avda. Pio XII, n 36, 31008 Pamplona, Spain
| | - Maria U Latasa
- Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, 31008 Pamplona, Spain
| | - Maddalen Jimenez
- Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, 31008 Pamplona, Spain
| | - Marina Barcena-Varela
- Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, 31008 Pamplona, Spain
| | - Eva Santamaría
- CIBERehd, Instituto de Salud Carlos III, Clinica Universidad de Navarra, Avda. Pio XII, n 36, 31008 Pamplona, Spain
| | - Raquel Urtasun
- Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, 31008 Pamplona, Spain
| | - Carlos Rodriguez-Ortigosa
- CIBERehd, Instituto de Salud Carlos III, Clinica Universidad de Navarra, Avda. Pio XII, n 36, 31008 Pamplona, Spain; Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, 31008 Pamplona, Spain
| | - Jesús Prieto
- CIBERehd, Instituto de Salud Carlos III, Clinica Universidad de Navarra, Avda. Pio XII, n 36, 31008 Pamplona, Spain; Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, 31008 Pamplona, Spain
| | - Pedro Berraondo
- Immunology and Immunotherapy Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, 31008 Pamplona, Spain
| | - Maite G Fernandez-Barrena
- CIBERehd, Instituto de Salud Carlos III, Clinica Universidad de Navarra, Avda. Pio XII, n 36, 31008 Pamplona, Spain; Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, 31008 Pamplona, Spain
| | - Carmen Berasain
- CIBERehd, Instituto de Salud Carlos III, Clinica Universidad de Navarra, Avda. Pio XII, n 36, 31008 Pamplona, Spain; Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, 31008 Pamplona, Spain.
| | - Matías A Avila
- CIBERehd, Instituto de Salud Carlos III, Clinica Universidad de Navarra, Avda. Pio XII, n 36, 31008 Pamplona, Spain; Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, 31008 Pamplona, Spain.
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Wang HK, Lai YC, Lin YH, Chiou HJ, Chou YH. Increased Stiffness of the Remnant Right Lobe Liver After Left Lobectomy or Lateral Segmentectomy in Donors of Living-Donor Liver Transplantation. Transplant Proc 2017; 49:1073-1075. [PMID: 28583530 DOI: 10.1016/j.transproceed.2017.03.046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
BACKGROUND Liver stiffness is associated with the degree of fibrosis along with other factors. Abrupt change of liver perfusion after hepatectomy is one such factor. In this study, we performed ultrasound elastography to explore the stiffness of the right lobe liver before and after hepatectomy in donors who underwent resection of left lobe or lateral segment of liver. METHODS A total of 32 left lobe liver donors (18 male and 14 female; age range, 21-55 years; mean age, 35.1 years; 19 left lobectomy with middle hepatic reserved for graft and 13 lateral segmentectomy with middle hepatic vein reserved in the remnant liver) were included in this study. Liver stiffness was measured by means of ultrasound elastography with the use of acoustic radiation force impulse imaging. Stiffness of the right lobe liver was obtained by means of right intercostal approach. RESULTS The stiffness of remnant right lobe liver significantly increased after hepatectomy (1.24 ± 0.18 vs 1.10 ± 0.13 m/s; P = .001). Donors of left lobe liver showed higher stiffness in the remnant right lobe liver compared with donors of lateral segment (1.30 ± 0.18 vs 1.15 ± 0.14 m/s; P = .027). There was no significant correlation between the remnant right lobe liver stiffness, postoperative liver function, and flow parameters of hepatic artery and portal vein. CONCLUSIONS The stiffness of remnant liver significantly increased after hepatectomy. Furthermore, the stiffness was higher in donors undergoing left lobectomy compared with those undergoing lateral segmentectomy.
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Affiliation(s)
- H-K Wang
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
| | - Y-C Lai
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Y-H Lin
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - H-J Chiou
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Y-H Chou
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan
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Living donor liver transplantation: eliminating the wait for death in end-stage liver disease? Nat Rev Gastroenterol Hepatol 2017; 14:373-382. [PMID: 28196987 DOI: 10.1038/nrgastro.2017.2] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Adult-to-adult living donor liver transplantation (A2ALDLT), outside of Asia, remains an important yet underutilized gift of life. For patients with end-stage liver disease, A2ALDLT is a proven transplantation option, with lower waiting list mortality and suffering, and equivalent or better allograft and patient survival than deceased-donor liver transplantation (DDLT). The risks to living donors and the benefit to their recipients have been carefully defined with long-term level 1 and 2 evidence-based study. An overview of the development and practice of living donor liver transplant (LDLT), including donor and recipient surgical allograft innovation, is provided. The issues of recipient selection, outcomes and morbidity, including disease-variable study and challenges past and present are presented in comparison with DDLT cohorts, and future insights are described. Central to practice is the careful and concise review of donor evaluation and selection and donor outcome, morbidity, quality of life and present and future strategies for donor advocacy and growth of the technique.
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de Jonge J, Olthoff KM. Liver regeneration. BLUMGART'S SURGERY OF THE LIVER, BILIARY TRACT AND PANCREAS, 2-VOLUME SET 2017:93-109.e7. [DOI: 10.1016/b978-0-323-34062-5.00006-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Jang S, Lee JM, Lee DH, Joo I, Yoon JH, Chang W, Han JK. Value of MR elastography for the preoperative estimation of liver regeneration capacity in patients with hepatocellular carcinoma. J Magn Reson Imaging 2016; 45:1627-1636. [PMID: 27859840 DOI: 10.1002/jmri.25517] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Accepted: 10/01/2016] [Indexed: 12/30/2022] Open
Abstract
PURPOSE To demonstrate the negative relationship between liver stiffness (LS) values measured at preoperative magnetic resonance elastography (MRE) and the regeneration capacity of the remnant liver after major hepatectomy, in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS Thirty-eight patients with HCC (mean age, 57.1) who had undergone liver computed tomography (CT) and 1.5T MRE prior to right hepatectomy were included in this retrospective study. CT volumetric analysis of total functional liver (calculated by subtracting tumor volume from total liver volume), future liver remnant (FLR), and postoperative liver remnant (LR) were performed using a semiautomatic analysis program. The regeneration index was expressed as [(VLR -VFLR )/VFLR ] × 100, where VLR is the volume of the liver remnant and VFLR is the volume of the FLR. The relationship between degree of LS measured at MRE and the regeneration index was assessed using the Spearman correlation test. RESULTS Average LS value at MRE increased along with hepatic fibrosis (HF) stage (r = 0.604, P < 0.001). At MRE, a cutoff value greater than 2.46 kPa yielded 90.0% sensitivity and 100% specificity in identifying HF stage 2 or greater (area under the curve [AUC], 0.95). Mean VFLR and VLR were 477.1 ± 147.5 mL and 911.9 ± 188.8 mL, respectively. The regeneration index of the liver remnant was 102.1 ± 58.2%. LS values at MRE and calculated regeneration index after right hepatectomy showed moderate negative correlation (r = -0.361, P = 0.026). CONCLUSION LS values measured at MRE may serve as a postoperative predictor of liver regeneration in patients with liver cirrhosis and HCC. LEVEL OF EVIDENCE 4 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;45:1627-1636.
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Affiliation(s)
- Siwon Jang
- Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Korea
| | - Dong Ho Lee
- Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Korea
| | - Ijin Joo
- Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Korea
| | - Jeong Hee Yoon
- Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Korea
| | - Won Chang
- Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Korea
| | - Joon Koo Han
- Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Korea
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Kageyama Y, Kokudo T, Amikura K, Miyazaki Y, Takahashi A, Sakamoto H. Impaired liver function attenuates liver regeneration and hypertrophy after portal vein embolization. World J Hepatol 2016; 8:1200-1204. [PMID: 27729956 PMCID: PMC5055589 DOI: 10.4254/wjh.v8.i28.1200] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2016] [Revised: 06/26/2016] [Accepted: 08/16/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To clarify the clinical factors associated with liver regeneration after major hepatectomy and the hypertrophic rate after portal vein embolization (PVE).
METHODS A total of 63 patients who underwent major hepatectomy and 13 patients who underwent PVE in a tertiary care hospital between January 2012 and August 2015 were included in the analysis. We calculated the remnant liver volume following hepatectomy using contrast-enhanced computed tomography (CT) performed before and approximately 3-6 mo after hepatectomy. Furthermore, we calculated the liver volume using CT performed 2-4 wk after PVE. Preoperative patient characteristics and laboratory data were analyzed to identify factors affecting postoperative liver regeneration or hypertrophy rate following PVE.
RESULTS The remnant liver volume/total liver volume ratio negatively correlated with the liver regeneration rate after hepatectomy (ρ = -0.850, P < 0.001). The regeneration rate was significantly lower in patients with an indocyanine green retention rate at 15 min (ICG-R15) of ≥ 20% in the right hepatectomy group but not in the left hepatectomy group. The hypertrophic rate after PVE positively correlated with the regeneration rate after hepatectomy (ρ = 0.648, P = 0.017). In addition, the hypertrophic rate after PVE was significantly lower in patients with an ICG-R15 ≥ 20% and a serum total bilirubin ≥ 1.5 mg/dL.
CONCLUSION The regeneration rate after major hepatectomy correlated with hypertrophic rate after PVE. Both of them were attenuated in the presence of impaired liver function.
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Braun HJ, Ascher NL, Roll GR, Roberts JP. Biliary complications following living donor hepatectomy. Transplant Rev (Orlando) 2016; 30:247-52. [PMID: 27531698 DOI: 10.1016/j.trre.2016.07.003] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Revised: 04/26/2016] [Accepted: 07/13/2016] [Indexed: 02/08/2023]
Abstract
BACKGROUND Living donor liver transplantation (LDLT) has become increasingly common in an effort to increase organ availability for the treatment of end-stage liver disease. Donor safety is a primary concern in LDLT. The majority of complications experienced by living donors are infectious or biliary in nature. The purpose of this paper was to review the existing literature on biliary complications in living donors. METHODS Studies were eligible for inclusion if they were published in English between 2006-present, focused on adult-to-adult LDLT, and were available via PubMed/MEDLINE. RESULTS A total of 33 studies reporting outcomes from 12,653 donors (right lobe: 8231, left lobe: 4422) were included. Of 33 studies, 12 reported outcomes from right lobe donors, 1 from left lobe donors, 14 compared left and right, and 6 focused specifically on biliary complications. A total of 830 biliary complications (6.6%) were reported, with 75 donors requiring re-operation for biliary complications and 1 donor death attributed to biliary complications. CONCLUSION Although bile leaks and strictures are still relatively common following living donor hepatectomy, the majority of complications are minor and resolve with conservative measures. Approximately 6% of living donors will experience a biliary complication and, of these 6%, approximately 9% (total of 0.6% of donors) will require operative management of the biliary complication.
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Affiliation(s)
- Hillary J Braun
- School of Medicine, University of California, San Francisco, San Francisco, CA
| | - Nancy L Ascher
- Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Garrett R Roll
- Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - John P Roberts
- Department of Surgery, University of California, San Francisco, San Francisco, CA.
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Segedi M, Dhani G, Ng VL, Grant D. Living Donors for Fulminant Hepatic Failure in Children. ACTA ACUST UNITED AC 2016. [DOI: 10.1007/978-3-319-29185-7_2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Young LH, Periwal V. Metabolic scaling predicts posthepatectomy liver regeneration after accounting for hepatocyte hypertrophy. Liver Transpl 2016; 22:476-84. [PMID: 26709233 PMCID: PMC4809762 DOI: 10.1002/lt.24392] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2015] [Revised: 10/28/2015] [Accepted: 12/14/2015] [Indexed: 01/28/2023]
Abstract
We adapted a mathematical model of posthepatectomy liver regeneration using data from a subset of patients in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study. The original model addressed changes in the number of quiescent, primed, and proliferating cells. Our adapted model takes into account hypertrophy of primed and replicating cells, and it is better able to predict liver volume. In addition, by building off the hypothesis that cell cycle parameters are approximately the same across all mammals, we found that changing only a single parameter characterizing metabolic load could model liver regeneration in 5 species of mammals. In conclusion, we improved a mathematical model of liver regeneration, predicted mammalian liver regeneration based on metabolism, and found correlations between model parameters and physiological measurements from liver donors.
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Affiliation(s)
- LeAnne H. Young
- Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Department of Health and Human Services; Bethesda MD
| | - Vipul Periwal
- Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Department of Health and Human Services; Bethesda MD
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Pamecha V, Mahansaria SS, Bharathy KGS, Kumar S, Sasturkar SV, Sinha PK, Sarin SK. Selection and outcome of the potential live liver donor. Hepatol Int 2016; 10:657-64. [DOI: 10.1007/s12072-016-9715-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Accepted: 02/11/2016] [Indexed: 01/21/2023]
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Aryal B, Shimizu T, Kadono J, Furoi A, Komokata T, Inoue M, Ikeda S, Fukukura Y, Nakamura M, Yamakuchi M, Hashiguchi T, Imoto Y. A Switch in the Dynamics of Intra-Platelet VEGF-A from Cancer to the Later Phase of Liver Regeneration after Partial Hepatectomy in Humans. PLoS One 2016; 11:e0150446. [PMID: 26930285 PMCID: PMC4773068 DOI: 10.1371/journal.pone.0150446] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Accepted: 02/15/2016] [Indexed: 12/31/2022] Open
Abstract
Background Liver regeneration (LR) involves an early inductive phase characterized by the proliferation of hepatocytes, and a delayed angiogenic phase distinguished by the expansion of non-parenchymal compartment. The interest in understanding the mechanism of LR has lately shifted from the proliferation and growth of parenchymal cells to vascular remodeling during LR. Angiogenesis accompanied by LR exerts a pivotal role to accomplish the process. Vascular endothelial growth factor (VEGF) has been elucidated as the most dynamic regulator of angiogenesis. From this perspective, platelet derived/Intra-platelet (IP) VEGF-A should be associated with LR. Material and Methods Thirty-seven patients diagnosed with hepatocellular carcinoma and undergoing partial hepatectomy (PH) were enrolled in the study. Serum and IP VEGF-A was monitored preoperatively and at four weeks of PH. Liver volumetry was determined on computer models derived from computed tomography (CT) scan. Results Serum and IP VEGF-A was significantly elevated at four weeks of PH. Preoperative IP VEGF-A was higher in patients with advanced cancer and vascular invasion. Postoperative IP VEGF-A was higher after major liver resection. There was a statistically significant correlation between postoperative IP VEGF-A and the future remnant liver volume. Moreover, the soluble vascular endothelial growth factor receptor-1 (sVEGFR1) was distinctly down-regulated suggesting a fine-tuned angiogenesis at the later phase of LR. Conclusion IP VEGF-A is overexpressed during later phase of LR suggesting its implications in inducing angiogenesis during LR.
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Affiliation(s)
- Bibek Aryal
- Cardiovascular and Gastroenterological Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Toshiaki Shimizu
- Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Jun Kadono
- Cardiovascular and Gastroenterological Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Akira Furoi
- Department of Surgery, Kirishima Medical Center, Kirishima, Japan
| | - Teruo Komokata
- Department of Surgery, Kagoshima Medical Center, National Hospital Organization, Kagoshima, Japan
| | - Maki Inoue
- Department of Surgery, Kirishima Medical Center, Kirishima, Japan
| | - Shunichiro Ikeda
- Department of Radiology, Kirishima Medical Center, Kirishima, Japan
| | - Yoshihiko Fukukura
- Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Masatoshi Nakamura
- Department of Clinical Laboratory, Kagoshima University Medical and Dental Hospital, Kagoshima, Japan
| | - Munekazu Yamakuchi
- Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Teruto Hashiguchi
- Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
- * E-mail:
| | - Yutaka Imoto
- Cardiovascular and Gastroenterological Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
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Sasturkar SV, David P, Sharma S, Sarin SK, Trehanpati N, Pamecha V. Serial changes of cytokines and growth factors in peripheral circulation after right lobe donor hepatectomy. Liver Transpl 2016; 22:344-51. [PMID: 26600439 DOI: 10.1002/lt.24373] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2015] [Revised: 10/29/2015] [Accepted: 11/03/2015] [Indexed: 12/28/2022]
Abstract
Cytokines and growth factors have prominent roles in liver regeneration. The aim of this study was to evaluate the biological markers of liver regeneration in healthy donors undergoing right lobe donor hepatectomy for living donor liver transplantation. Twenty-five voluntary liver donors were enrolled. Peripheral blood samples were taken a day before the operation and on postoperative days (PODs) 1, 3, 7, 14, and 42. Levels of hepatocyte growth factor (HGF), interleukin (IL) 6, tumor necrosis factor α (TNF-α), thrombopoietin (TPO), transforming growth factor β1 (TGF-β1), interferon (IFN) α, and IFNγ were monitored. The remnant liver volume (RLV) before surgery and regeneration liver volume (RgV) on POD 14 were calculated on computed tomography (CT). RgV/RLV ratio was correlated with the remnant-liver-volume-to-body-weight ratio (RLVBWR). Inverse correlation was observed between RgV/RLV and RLVBWR (r(2) = 0.61; P < 0.001). There was a significant rise of HGF on POD 1 (P = 0.001), POD 7 (P = 0.049), and POD 14 (P = 0.04). TNF-α was elevated on POD 1 (P = 0.004). The levels of IL 6 (P < 0.001) and TPO (P < 0.001) were higher from POD 1 to POD 42. IFNα was higher on POD 14 (P = 0.003) and POD 42 (P = 0.001). There was a significant fall of IFNγ on POD 1 (P = 0.01) and increase on POD 14 (P = 0.04). The levels of TGF-β1 were higher on POD 14 (P = 0.008) and on POD 42 (P = 0.002). In conclusion, HGF, IL 6, TNF-α, and TPO are involved in the early phase, whereas TGF-β1 and IFN are involved in the termination phase of liver regeneration. Liver regeneration was observed to be higher in donors with low RLVBWR.
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Affiliation(s)
| | - Paul David
- Department of Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shreya Sharma
- Department of Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Nirupama Trehanpati
- Department of Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Viniyendra Pamecha
- Departments of Liver Transplantation and Hepato-Pancreato-Biliary Surgery, New Delhi, India
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44
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Duclos J, Bhangui P, Salloum C, Andreani P, Saliba F, Ichai P, Elmaleh A, Castaing D, Azoulay D. Ad Integrum Functional and Volumetric Recovery in Right Lobe Living Donors: Is It Really Complete 1 Year After Donor Hepatectomy? Am J Transplant 2016; 16:143-56. [PMID: 26280997 DOI: 10.1111/ajt.13420] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2014] [Revised: 05/27/2015] [Accepted: 06/11/2015] [Indexed: 02/07/2023]
Abstract
The partial liver's ability to regenerate both as a graft and remnant justifies right lobe (RL) living donor liver transplantation. We studied (using biochemical and radiological parameters) the rate, extent of, and predictors of functional and volumetric recovery of the remnant left liver (RLL) during the first year in 91 consecutive RL donors. Recovery of normal liver function (prothrombin time [PT] ≥70% of normal and total bilirubin [TB] ≤20 µmol/L), liver volumetric recovery, and percentage RLL growth were analyzed. Normal liver function was regained by postoperative day's 7, 30, and 365 in 52%, 86%, and 96% donors, respectively. Similarly, mean liver volumetric recovery was 64%, 71%, and 85%; whereas the percentage liver growth was 85%, 105%, and 146%, respectively. Preoperative PT value (p = 0.01), RLL/total liver volume (TLV) ratio (p = 0.03), middle hepatic vein harvesting (p = 0.02), and postoperative peak TB (p < 0.01) were predictors of early functional recovery, whereas donor age (p = 0.03), RLL/TLV ratio (p = 0.004), and TLV/ body weight ratio (p = 0.02) predicted early volumetric recuperation. One-year post-RL donor hepatectomy, though functional recovery occurs in almost all (96%), donors had incomplete restoration (85%) of preoperative total liver volume. Modifiable predictors of regeneration could help in better and safer donor selection, while continuing to ensure successful recipient outcomes.
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Affiliation(s)
- J Duclos
- Centre Hépato-Biliaire, Assistance Publique-Hôpitaux de Paris, Hôpital Paul Brousse, Villejuif, France
| | - P Bhangui
- Centre Hépato-Biliaire, Assistance Publique-Hôpitaux de Paris, Hôpital Paul Brousse, Villejuif, France
| | - C Salloum
- Centre Hépato-Biliaire, Assistance Publique-Hôpitaux de Paris, Hôpital Paul Brousse, Villejuif, France
| | - P Andreani
- Centre Hépato-Biliaire, Assistance Publique-Hôpitaux de Paris, Hôpital Paul Brousse, Villejuif, France
| | - F Saliba
- Centre Hépato-Biliaire, Assistance Publique-Hôpitaux de Paris, Hôpital Paul Brousse, Villejuif, France
| | - P Ichai
- Centre Hépato-Biliaire, Assistance Publique-Hôpitaux de Paris, Hôpital Paul Brousse, Villejuif, France
| | - A Elmaleh
- Service de Radiologie, Assistance Publique-Hôpitaux de Paris, Hôpital Paul Brousse, Villejuif, France
| | - D Castaing
- Centre Hépato-Biliaire, Assistance Publique-Hôpitaux de Paris, Hôpital Paul Brousse, Villejuif, France
| | - D Azoulay
- Centre Hépato-Biliaire, Assistance Publique-Hôpitaux de Paris, Hôpital Paul Brousse, Villejuif, France.,Unité INSERM 1004, Villejuif, France
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45
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Cook D, Ogunnaike BA, Vadigepalli R. Systems analysis of non-parenchymal cell modulation of liver repair across multiple regeneration modes. BMC SYSTEMS BIOLOGY 2015; 9:71. [PMID: 26493454 PMCID: PMC4618752 DOI: 10.1186/s12918-015-0220-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Accepted: 10/10/2015] [Indexed: 12/27/2022]
Abstract
Background A hallmark of chronic liver disease is the impairment of the liver’s innate regenerative ability. In this work we use a computational approach to unravel the principles underlying control of liver repair following an acute physiological challenge. Methods We used a mathematical model of inter- and intra-cellular interactions during liver regeneration to infer key molecular factors underlying the dysregulation of multiple regeneration modes, including delayed, suppressed, and enhanced regeneration. We used model analysis techniques to identify organizational principles governing the cellular regulation of liver regeneration. We fit our model to several published data sets of deficient regeneration in rats and healthy regeneration in humans, rats, and mice to predict differences in molecular regulation in disease states and across species. Results Analysis of the computational model pointed to an important balance involving inflammatory signals and growth factors, largely produced by Kupffer cells and hepatic stellate cells, respectively. Our model analysis results also indicated an organizational principle of molecular regulation whereby production rate of molecules acted to induce coarse-grained control of signaling levels while degradation rate acted to induce fine-tuning control. We used this computational framework to investigate hypotheses concerning molecular regulation of regeneration across species and in several chronic disease states in rats, including fructose-induced steatohepatitis, alcoholic steatohepatitis, toxin-induced cirrhosis, and toxin-induced diabetes. Our results indicate that altered non-parenchymal cell activation is sufficient to explain deficient regeneration caused by multiple disease states. We also investigated liver regeneration across mammalian species. Our results suggest that non-invasive measures of liver regeneration taken at 30 days following resection could differentiate between several hypotheses about how human liver regeneration differs from rat regeneration. Conclusions Overall, our results provide a new computational platform integrating a wide range of experimental information, with broader utility in exploring the dynamic patterns of liver regeneration across species and over multiple chronic diseases. Electronic supplementary material The online version of this article (doi:10.1186/s12918-015-0220-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Daniel Cook
- Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA. .,Daniel Baugh Institute for Functional Genomics/Computational Biology, Department of Cell and Developmental Biology, Thomas Jefferson University, Philadelphia, PA, USA.
| | - Babatunde A Ogunnaike
- Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA.
| | - Rajanikanth Vadigepalli
- Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA. .,Daniel Baugh Institute for Functional Genomics/Computational Biology, Department of Cell and Developmental Biology, Thomas Jefferson University, Philadelphia, PA, USA.
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46
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Kakisaka K, Kataoka K, Onodera M, Suzuki A, Endo K, Tatemichi Y, Kuroda H, Ishida K, Takikawa Y. Alpha-fetoprotein: A biomarker for the recruitment of progenitor cells in the liver in patients with acute liver injury or failure. Hepatol Res 2015; 45:E12-20. [PMID: 25376981 DOI: 10.1111/hepr.12448] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2014] [Revised: 10/28/2014] [Accepted: 10/28/2014] [Indexed: 12/12/2022]
Abstract
AIM The optimal conditions for hepatocyte proliferation should be clarified in an attempt to improve the impaired liver regeneration observed in patients with acute liver failure (ALF). In order to evaluate the significance of the serum α-fetoprotein (AFP). level and prothrombin time international normalized ratio (PT-INR) as possible biomarkers of the proliferation of liver stem/progenitor cells (LPC) and mature hepatocytes (MH), respectively, we focused on donors of living donor liver transplantation (LDLT) and patients with acute liver injury (ALI), including ALF. METHODS Seventy-three patients with ALI/ALF and 11 donors for LDLT were evaluated. LPC induction was histologically evaluated using cytokeratin (CK)-7 staining in 45 ALI/ALF patients. RESULTS The AFP level was not apparently elevated during the observation period in any of the LDLT donors, whereas the serum AFP levels were substantially increased in the patients with ALI/ALF and significantly correlated with the number of CK-7 positive LPC in the liver, except for very severe damaged liver. All patients exhibiting an early peak in the AFP level prior to PT-INR elevation died. CONCLUSION The serum AFP level may reflect the induction of LPC in ALI/ALF patients. The substantial and persistent induction of LPC until sufficient regeneration of MH may be needed for a recovery from ALF. We herein demonstrate that the serum AFP level may be a serum marker of LPC in patients with ALI/ALF. A comparison of the serial changes in the AFP levels and PT-INR in our study patients showed impaired proliferation of LPC and delayed recovery of MH in the patients who died.
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Affiliation(s)
- Keisuke Kakisaka
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Kojiro Kataoka
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Mio Onodera
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Akiko Suzuki
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Kei Endo
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Yoshinori Tatemichi
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Hidekatsu Kuroda
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Kazuyuki Ishida
- Department of Molecular Diagnostic Pathology, Iwate Medical University, Morioka, Japan
| | - Yasuhiro Takikawa
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
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Croome KP, Hernandez-Alejandro R, Parker M, Heimbach J, Rosen C, Nagorney DM. Is the liver kinetic growth rate in ALPPS unprecedented when compared with PVE and living donor liver transplant? A multicentre analysis. HPB (Oxford) 2015; 17:477-84. [PMID: 25728543 PMCID: PMC4430776 DOI: 10.1111/hpb.12386] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2014] [Accepted: 12/12/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND The clinical perspective on hepatic growth is limited. The goal of the present study was to compare hepatic hypertrophy and the kinetic growth rate(KGR) in patients after the ALPPS (Associating Liver Partition with Portal Vein Ligation for Staged Hepatectomy) procedure, portal vein embolization (PVE) and living donor liver transplantation. METHODS Volumetry and KGR of the future liver remnant (FLR) were compared from (15) patients undergoing ALPPS, (53) patients undergoing PVE, (90) recipients of living donor liver grafts and (93) donors of living donor liver grafts. RESULTS The degree of hypertrophy was significantly greater after ALPPS (84.3 ± 7.8%) than after PVE (36.0 ± 27.2%) (P < 0.001). The KGR was also significantly greater for ALPPS [32.7 ± 13.6 cubic centimetres (cc)/day] (10.8 ± 4.5%/day) compared with PVE (4.4 ± 3.2 cc/day) (0.98 ± 0.75%/day) (P < 0.001). The FLR of living donor donors had the greatest degree of hypertrophy (107.5 ± 39.2%) and was greater than after ALPPS (P = 0.02), PVE (P < 0.001) and in living donor-recipient grafts (P < 0.001). KGR (cc/day) was greater in FLR of living donor donors compared with both ALPPS (P < 0.001) and PVE (P < 0.001). The KGR in patients undergoing ALPPS and living donor liver transplantation had a linear relationship with the size of FLR. CONCLUSION FLR hypertrophy and KGR were greater after ALPPS than PVE. However, the degree of hypertrophy after ALPPS is not unprecedented, as KGR in the FLR from living donor donors is equal to or greater than after ALPPS. The KGR of the FLR in patients after ALPPS and living donor donors correlates directly with the size of the FLR.
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Affiliation(s)
- Kristopher P Croome
- Divisions of Gastroenterologic and General Surgery, Mayo ClinicRochester, MN, USA
- Department of Transplantation, Mayo ClinicJacksonville, FL, USA
| | | | - Maile Parker
- Divisions of Gastroenterologic and General Surgery, Mayo ClinicRochester, MN, USA
| | - Julie Heimbach
- Division of Transplantation Surgery and Mayo Clinic William J. von Liebig Transplant Center, Mayo ClinicRochester, MN, USA
| | - Charles Rosen
- Division of Transplantation Surgery and Mayo Clinic William J. von Liebig Transplant Center, Mayo ClinicRochester, MN, USA
| | - David M Nagorney
- Divisions of Gastroenterologic and General Surgery, Mayo ClinicRochester, MN, USA
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48
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Radtke A, Sgourakis G, Molmenti EP, Beckebaum S, Cicinnati VR, Schmidt H, Peitgen HO, Broelsch CE, Malagó M, Schroeder T. Risk of venous congestion in live donors of extended right liver graft. World J Gastroenterol 2015; 21:6008-6017. [PMID: 26019467 PMCID: PMC4438037 DOI: 10.3748/wjg.v21.i19.6008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2014] [Revised: 02/01/2015] [Accepted: 04/03/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate middle hepatic vein (MHV) management in adult living donor liver transplantation and safer remnant volumes (RV).
METHODS: There were 59 grafts with and 12 grafts without MHV (including 4 with MHV-5/8 reconstructions). All donors underwent our five-step protocol evaluation containing a preoperative protocol liver biopsy Congestive vs non-congestive RV, remnant-volume-body-weight ratios (RVBWR) and postoperative outcomes were evaluated in 71 right graft living donors. Dominant vs non-dominant MHV anatomy in total liver volume (d-MHV/TLV vs nd-MHV/TLV) was constellated with large/small congestion volumes (CV-index). Small for size (SFS) and non-SFS remnant considerations were based on standard cut-off- RVBWR and RV/TLV. Non-congestive RVBWR was based on non-congestive RV.
RESULTS: MHV and non-MHV remnants showed no significant differences in RV, RV/TLV, RVBWR, total bilirubin, or INR. SFS-remnants with RV/TLV < 30% and non-SFS-remnants with RV/TLV ≥ 30% showed no significant differences either. RV and RVBWR for non-MHV (n = 59) and MHV-containing (n = 12) remnants were 550 ± 95 mL and 0.79 ± 0.1 mL vs 568 ± 97 mL and 0.79 ± 0.13, respectively (P = 0.423 and P = 0.919. Mean left RV/TLV was 35.8% ± 3.9%. Non-MHV (n = 59) and MHV-containing (n = 12) remnants (34.1% ± 3% vs 36% ± 4% respectively, P = 0.148. Eight SFS-remnants with RVBWR < 0.65 had a significantly smaller RV/TLV than 63 non-SFS-remnants with RVBWR ≥ 0.65 [SFS: RV/TLV 32.4% (range: 28%-35.7%) vs non-SFS: RV/TLV 36.2% (range: 26.1%-45.5%), P < 0.009. Six SFS-remnants with RV/TLV < 30% had significantly smaller RVBWR than 65 non-SFS-remnants with RV/TLV ≥ 30% (0.65 (range: 0.6-0.7) vs 0.8 (range: 0.6-1.27), P < 0.01. Two (2.8%) donors developed reversible liver failure. RVBWR and RV/TLV were concordant in 25%-33% of SFS and in 92%-94% of non-SFS remnants. MHV management options including complete MHV vs MHV-4A selective retention were necessary in n = 12 vs n = 2 remnants based on particularly risky congestive and non-congestive volume constellations.
CONCLUSION: MHV procurement should consider individual remnant congestive- and non-congestive volume components and anatomy characteristics, RVBWR-RV/TLV constellation enables the identification of marginally small remnants.
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Emond JC, Fisher RA, Everson G, Samstein B, Pomposelli JJ, Zhao B, Forney S, Olthoff KM, Baker TB, Gillespie BW, Merion RM. Changes in liver and spleen volumes after living liver donation: a report from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). Liver Transpl 2015; 21:151-61. [PMID: 25488878 PMCID: PMC4308432 DOI: 10.1002/lt.24062] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2014] [Revised: 10/21/2014] [Accepted: 10/26/2014] [Indexed: 02/02/2023]
Abstract
Previous reports have drawn attention to persistently decreased platelet counts among liver donors. We hypothesized an etiologic association between altered platelet counts and postdonation splenomegaly and sought to explore this relationship. This study analyzed de-identified computed tomography/magnetic resonance scans of 388 donors from 9 Adult-to-Adult Living Donor Liver Transplantation Cohort Study centers read at a central computational image analysis laboratory. Resulting liver and spleen volumes were correlated with time-matched clinical laboratory values. Predonation liver volumes varied 2-fold in healthy subjects, even when they were normalized by the body surface area (BSA; range = 522-1887 cc/m(2) , n = 346). At month 3 (M3), postdonation liver volumes were, on average, 79% of predonation volumes [interquartile range (IQR) = 73%-86%, n = 165] and approached 88% at year 1 (Y1; IQR = 80%-93%, n = 75). The mean spleen volume before donation was 245 cc (n = 346). Spleen volumes greater than 100% of the predonation volume occurred in 92% of donors at M3 (n = 165) and in 88% at Y1 after donation (n = 75). We sought to develop a standard spleen volume (SSV) model to predict normal spleen volumes in donors before donation and found that decreased platelet counts, a younger age, a higher predonation liver volume, higher hemoglobin levels, and a higher BSA predicted a larger spleen volume (n = 344, R(2) = 0.52). When this was applied to postdonation values, some large volumes were underpredicted by the SSV model. Models developed on the basis of the reduced sample of postdonation volumes yielded smaller underpredictions. These findings confirm previous observations of thrombocytopenia being associated with splenomegaly after donation. The results of the SSV model suggest that the biology of this phenomenon is complex. This merits further long-term mechanistic studies of liver donors with an investigation of the role of other factors such as thrombopoietin and exposure to viral infections to better understand the evolution of the spleen volume after liver donation.
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Affiliation(s)
- Jean C. Emond
- Columbia University, Center for Liver Disease and Transplantation, New York, NY
| | - Robert A. Fisher
- Department of Surgery, Virginia Commonwealth University, Richmond, VA, Transplant Institute, Harvard Medical School, Boston, MA
| | - Gregory Everson
- Section of Hepatology, University of Colorado Denver, Aurora, CO
| | - Benjamin Samstein
- Columbia University, Center for Liver Disease and Transplantation, New York, NY
| | - James J. Pomposelli
- Department of Transplantation, Lahey Hospital and Medical Center, Burlington, MA
| | - Binsheng Zhao
- Department of Radiology, Columbia University Medical Center, New York, NY
| | - Sarah Forney
- Arbor Research Collaborative for Health, Ann Arbor, MI
| | - Kim M. Olthoff
- Department of Surgery, University of Pennsylvania, Philadelphia, PA
| | - Talia B. Baker
- Department of Surgery, Northwestern University, Chicago, IL
| | | | - Robert M. Merion
- Arbor Research Collaborative for Health, Ann Arbor, MI, Department of Surgery, University of Michigan, Ann Arbor, MI
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50
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Alkhouli M, Gagel A, Mathur M, O'Murchu B. Platypnea-orthodeoxia syndrome: an unusual complication of partial liver resection. Intern Med 2015; 54:1067-9. [PMID: 25948349 DOI: 10.2169/internalmedicine.54.3617] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Platypnea-orthodeoxia syndrome (POS) is a rare syndrome of severe hypoxemia upon assuming an upright position. It is classically described as shunting from the right atrium to the left atrium usually via a patent foramen ovale (PFO). Alterations in the intrathoracic anatomy after liver resection and regeneration may trigger this condition in patients with clinically silent PFO -a previously unreported cause of POS.
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