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Impey ORE, Baker JD, Smyth RS, Potts SG. Death after psychiatric contraindications to urgent liver transplant for paracetamol overdose. World J Transplant 2025; 15:101865. [DOI: 10.5500/wjt.v15.i3.101865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Revised: 02/20/2025] [Accepted: 02/25/2025] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND Paracetamol overdose (POD) is the most common cause of acute hepatic failure (AHF) in the United Kingdom. Without urgent orthotopic liver transplant (OLT), mortality is high. Psychiatric assessment for transplant is time-pressured and often undertaken by psychiatrists without transplant experience. Assessors may identify absolute psychiatric contraindications (APCIs) precluding transplant in otherwise medically suitable patients. It is unknown how often this occurs. The combination of high but unknown mortality, time pressure, and relative inexperience is likely to provoke anxiety in assessors. This study hypothesised that the proportion of POD patients assessed for OLT who die because psychiatric contraindications preclude transplant would be small but not negligible.
AIM To determine the proportion of patients with paracetamol-induced AHF, for whom psychiatric contraindications preclude transplantation, and the consequent mortality.
METHODS This is an 18-year single-centre retrospective cohort study based in a national liver transplant centre. 524 participants were identified from a departmental database and included if they had AHF from suspected POD and received a psychiatric assessment for OLT. For those who died before discharge, records were reviewed for medical and psychiatric contraindications to transplant, alongside age, sex, and primary psychiatric diagnosis. We calculated the proportion of patients assessed for whom APCIs precluded transplant, resulting in death.
RESULTS Among 524 patients undergoing psychiatric assessment for OLT, there were 102 in-episode deaths (19.5%). APCIs were identified in 46 patients who were otherwise medically suitable for transplant and went on to die. This statistic represents 8.8% of the number of persons evaluated and 45% of the number of deaths. Within this subgroup, 27 (59%) were female, with a mean age of 44.6 years (ranging from 19-72 years). The most common primary psychiatric diagnosis was alcohol dependence syndrome, which accounted for 67% (n = 31).
CONCLUSION 8.8% of medically suitable patients with AHF following POD died with APCIs to transplant. This indicates a need for ongoing assessor training and support, and (inter) national comparisons of practice.
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Affiliation(s)
- Olivia R E Impey
- Hammersmith and Fulham Mental Health Unit, West London NHS Trust, London W6 8LN United Kingdom
| | - Jennifer D Baker
- Department of Psychological Medicine, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, United Kingdom
| | - Roger S Smyth
- Department of Psychological Medicine, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, United Kingdom
| | - Stephen G Potts
- Department of Psychological Medicine, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, United Kingdom
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2
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Wu TW, Hou TY, Yang JCS, Wang CC. First report of successful liver transplantation following supermicrosurgical lymphaticovenous anastomoses for lymphorrhea with intractable infection: A case report. World J Transplant 2025; 15:101496. [DOI: 10.5500/wjt.v15.i3.101496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 12/30/2024] [Accepted: 02/06/2025] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND Liver transplant (LT) candidates face a heightened risk of infection both pre- and post-transplant, owing to immunosuppressive therapy and complications from chronic liver disease. Infections during the pre-transplant period, such as lymphorrhea-induced cellulitis, can cause significant delays in transplantation and increase mortality while on the waiting list. Lymphorrhea, characterized by substantial lymphatic leakage and recurrent skin infections, presents a significant challenge in managing patients who are already immunocompromised. Effective preoperative infection control is critical to enhancing the prospects for a successful liver transplantation.
CASE SUMMARY We report the case of a 50-year-old female diagnosed with Hepatitis C virus-related cirrhosis (Child-Pugh C) and recurrent cellulitis due to lymphorrhea in her left lower leg. She suffered repeated episodes of cellulitis over five years, which prevented her from undergoing LT. Initial conservative treatments were unsuccessful in managing the lymphatic leakage and accompanying infections. In February 2019, she underwent supermicrosurgical lymphaticovenous anastomoses (LVA) to address her lymphorrhea. This procedure, which created multiple lymphatic-venous connections in the lower limb, led to significant improvements in her condition. After the LVA, she experienced no further episodes of cellulitis. Eighteen months later, she successfully underwent a deceased donor liver transplantation. Postoperative complications, including a wound hematoma, were effectively managed, and she was discharged 3 months post-operation. At her 3-year follow-up, her liver function was stable, with no recurrence of cellulitis.
CONCLUSION Despite numerous challenges, the patient achieved a successful recovery with satisfactory graft function and was free from lymphorrhea/lymphedema in her left lower limb 3 years post-transplantation. This case underscores the importance of robust infection control during both the pre- and post-transplantation phases and highlights the potential of LVA as a treatment option for managing lymphorrhea and infections in patients with liver cirrhosis.
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Affiliation(s)
- Tse-Wei Wu
- Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833401, Taiwan
| | - Teng-Yuan Hou
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan
| | - Johnson Chia-Shen Yang
- Department of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan
| | - Chih-Chi Wang
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan
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3
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Hayes A, McCormick E, McNally M. Use of indwelling pleural catheter in a patient with refractory left-sided hepatic hydrothorax. BMJ Case Rep 2025; 18:e259867. [PMID: 40107735 DOI: 10.1136/bcr-2024-259867] [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] [Indexed: 03/22/2025] Open
Abstract
A female patient in her mid-50s presented with left-sided effusion in the context of decompensated cirrhosis secondary to alcoholic hepatitis. She had a pre-existing injury to her left hemidiaphragm following a fall 2 years previously, at which point she had also developed a left-sided effusion. The diagnosis of hepatic hydrothorax (HH) was made following pleural fluid aspiration. Recurrent thoracocentesis was not sufficient to manage the effusion and diuretic use was limited by hyponatraemia. An indwelling pleural catheter (IPC) was subsequently inserted to facilitate routine drainage and management in the outpatient setting. To our knowledge, this is the first instance of IPC insertion for HH in Ireland.
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Affiliation(s)
- Anna Hayes
- Gastroenterology, Midlands Regional Hospital Tullamore, Tullamore, Ireland
| | - Emma McCormick
- Gastroenterology, Midlands Regional Hospital Tullamore, Tullamore, Ireland
| | - Mairead McNally
- Gastroenterology, Midlands Regional Hospital Tullamore, Tullamore, Ireland
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Wang MC, Bui A, Tintara S, Etesami K, Kim B. Recurrent Bacteremia and Cholangitis From Eroded Hepatic Artery Pseudoaneurysm Coil Into the Common Hepatic Duct: A Rare Indication for Liver Transplantation. ACG Case Rep J 2025; 12:e01590. [PMID: 39790174 PMCID: PMC11717500 DOI: 10.14309/crj.0000000000001590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Accepted: 12/17/2024] [Indexed: 01/12/2025] Open
Abstract
Liver transplant may be necessary to manage infectious complications from severe structural biliary disease. In this report, we describe a 71-year-old woman with history of coil-embolized hepatic artery pseudoaneurysm who subsequently developed biliary obstruction resulting from coil erosion into the common hepatic duct. Resultant complications included recurrent cholangitis, bacteremia, and numerous hepatic abscesses. Because of lack of improvement with medical management, the patient underwent liver transplantation and coil removal as the definitive treatment modality. Altogether, this report explores a unique case of liver transplantation as source control for a patient with an active disseminated infection.
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Affiliation(s)
- Mark C. Wang
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Aileen Bui
- Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Supisara Tintara
- Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Kambiz Etesami
- Department of Surgery, Division of Hepatopancreaticobiliary Surgery and Abdominal Organ Transplantation, Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Brian Kim
- Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA
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Babikir MM, Alkhalaf MH, Al Bahili HM, Babiker MM, Alyami AA, Alrashed AI, Alhajeri AA, Alkhelaiwi NM. Role of sonography in detection and evaluation of post liver transplant complications. Saudi Med J 2024; 45:1041-1048. [PMID: 39379125 PMCID: PMC11463573 DOI: 10.15537/smj.2024.45.10.20240320] [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: 05/15/2024] [Accepted: 08/30/2024] [Indexed: 10/10/2024] Open
Abstract
OBJECTIVES To evaluate the role of sonography in revealing and characterizing liver transplant complications based on gray scale and color Doppler, describe the normal Doppler findings, and discuss the significance of distinguishing normal transient changes in the spectral waveform from findings that may suggests ominous complications. METHODS We carried out a retrospective cross-sectional study at Prince Sultan Military Medical City, Riyadh, Saudi Arabia. The medical records and imaging studies of a total of 122 candidates who underwent transplantation between January 2016 to February 2022 were reviewed. RESULTS Our results showed that most patients were males with the most frequent age group being those between 54-71 years. Hepatitis B virus and hepatic cellular carcinoma were the most common indications for transplants. A total of 95 patients received a graft from a living related donor. Regarding complications, biliary issues (including leaks and ducts dilation) were the second most frequent complication after collections. Vascular complications represented 7.4% of all complications and was the leading cause of death in 4.8% of cases. Among all vascular issues encountered during liver transplant, portal vein thrombosis was the most predominant. In respect to Doppler findings, portal vein velocities and resistive index of hepatic artery had re-averaged within 7-10 post-operative days in most patients. CONCLUSION Ultrasound plays crucial role in the post-operative management of compilations, facilitating early detection, which is substantial for the graft survival.
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Affiliation(s)
- Muna M. Babikir
- From the Department of Radiodaignostic (Babikir, Alkhalaf, Alrashed, Alhajeri, Alkhelaiwi), Ultrasound Section; from the Multi-organ Transplant Center (Al Bahili, Alyami), Prince Sultan Military Medical City, and from the Department of Radiology (Babiker), Ultrasound Section, Althomairy Clinic, Riyadh, Kingdom of Saudi Arabia.
| | - Mohammed H. Alkhalaf
- From the Department of Radiodaignostic (Babikir, Alkhalaf, Alrashed, Alhajeri, Alkhelaiwi), Ultrasound Section; from the Multi-organ Transplant Center (Al Bahili, Alyami), Prince Sultan Military Medical City, and from the Department of Radiology (Babiker), Ultrasound Section, Althomairy Clinic, Riyadh, Kingdom of Saudi Arabia.
| | - Hamad M. Al Bahili
- From the Department of Radiodaignostic (Babikir, Alkhalaf, Alrashed, Alhajeri, Alkhelaiwi), Ultrasound Section; from the Multi-organ Transplant Center (Al Bahili, Alyami), Prince Sultan Military Medical City, and from the Department of Radiology (Babiker), Ultrasound Section, Althomairy Clinic, Riyadh, Kingdom of Saudi Arabia.
| | - Magda M. Babiker
- From the Department of Radiodaignostic (Babikir, Alkhalaf, Alrashed, Alhajeri, Alkhelaiwi), Ultrasound Section; from the Multi-organ Transplant Center (Al Bahili, Alyami), Prince Sultan Military Medical City, and from the Department of Radiology (Babiker), Ultrasound Section, Althomairy Clinic, Riyadh, Kingdom of Saudi Arabia.
| | - Ali A. Alyami
- From the Department of Radiodaignostic (Babikir, Alkhalaf, Alrashed, Alhajeri, Alkhelaiwi), Ultrasound Section; from the Multi-organ Transplant Center (Al Bahili, Alyami), Prince Sultan Military Medical City, and from the Department of Radiology (Babiker), Ultrasound Section, Althomairy Clinic, Riyadh, Kingdom of Saudi Arabia.
| | - Abdulaziz I. Alrashed
- From the Department of Radiodaignostic (Babikir, Alkhalaf, Alrashed, Alhajeri, Alkhelaiwi), Ultrasound Section; from the Multi-organ Transplant Center (Al Bahili, Alyami), Prince Sultan Military Medical City, and from the Department of Radiology (Babiker), Ultrasound Section, Althomairy Clinic, Riyadh, Kingdom of Saudi Arabia.
| | - Abdullah A. Alhajeri
- From the Department of Radiodaignostic (Babikir, Alkhalaf, Alrashed, Alhajeri, Alkhelaiwi), Ultrasound Section; from the Multi-organ Transplant Center (Al Bahili, Alyami), Prince Sultan Military Medical City, and from the Department of Radiology (Babiker), Ultrasound Section, Althomairy Clinic, Riyadh, Kingdom of Saudi Arabia.
| | - Najla M. Alkhelaiwi
- From the Department of Radiodaignostic (Babikir, Alkhalaf, Alrashed, Alhajeri, Alkhelaiwi), Ultrasound Section; from the Multi-organ Transplant Center (Al Bahili, Alyami), Prince Sultan Military Medical City, and from the Department of Radiology (Babiker), Ultrasound Section, Althomairy Clinic, Riyadh, Kingdom of Saudi Arabia.
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6
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Mathis S, Putzer G, Gasteiger L, Eschertzhuber S, Schneeberger S, Cardini B, Hell T, Martini J. Normothermic Machine Perfusion Reduces Transfusion Requirements Even After Static Cold Storage: A 1 y Retrospective Single-center Analysis. Transplant Direct 2024; 10:e1628. [PMID: 38757047 PMCID: PMC11098234 DOI: 10.1097/txd.0000000000001628] [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: 09/25/2023] [Revised: 01/26/2024] [Accepted: 02/15/2024] [Indexed: 05/18/2024] Open
Abstract
Background Normothermic machine perfusion (NMP) of liver grafts has been shown to reduce intraoperative catecholamine consumption and the need for allogenic blood products after reperfusion compared with organs undergoing classical static cold storage (SCS). This study aimed to investigate the effects of an NMP phase after SCS (NMP after SCS) of liver grafts in terms of postreperfusion hemodynamics and transfusion requirements. Methods Eighteen recipients of NMP after SCS grafts were matched according to recipient age, donor age, and model for end-stage liver disease score in a 1:2 ratio with recipients of an SCS graft. Postreperfusion hemodynamics and the need for catecholamines, blood products, and clotting factors were compared. Results After reperfusion of the organ, patients in the NMP after SCS group showed significantly reduced transfusion requirements for packed red blood cells and platelet concentrates compared with patients of the SCS group (P < 0.001 and P = 0.018, respectively). In addition, patients in the NMP after SCS group received less fibrinogen concentrate (NMP after SCS group 0 [0-1.5] g versus SCS group 2 [0-4] g; P = 0.0163). No differences in postreperfusion hemodynamics could be detected between groups. Conclusions This retrospective analysis shows that NMP reduces postreperfusion requirements of red blood cells, platelet concentrates, and fibrinogen concentrate even if installed after a phase of organ SCS, because it may be practiced on most centers where NMP is available.
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Affiliation(s)
- Simon Mathis
- Department of Anaesthesiology and Critical Care Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Gabriel Putzer
- Department of Anaesthesiology and Critical Care Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Lukas Gasteiger
- Department of Anaesthesiology and Critical Care Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Stephan Eschertzhuber
- Department of Anaesthesiology and Intensive Care Medicine, Hospital Hall in Tirol, Austria
| | - Stefan Schneeberger
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Benno Cardini
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | | | - Judith Martini
- Department of Anaesthesiology and Critical Care Medicine, Medical University of Innsbruck, Innsbruck, Austria
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7
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Mishra S, Taneja S. Algorithmic Approach to Deranged Liver Functions After Transplantation. J Clin Exp Hepatol 2024; 14:101317. [PMID: 38264576 PMCID: PMC10801315 DOI: 10.1016/j.jceh.2023.101317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Accepted: 12/06/2023] [Indexed: 01/25/2024] Open
Abstract
Liver transplant (LT) recipients require close follow-up with regular monitoring of the liver function tests (LFTs). Evaluation of deranged LFT should be individualized depending upon the time since LT, peri-operative events, clinical course, and any complications. These derangements can range from mild and asymptomatic to severe and symptomatic elevations requiring expedited personalized assessment and management. Pattern of LFT derangement (hepatocellular, cholestatic, or mixed), donor-recipient risk factors, timing after LT (post-operative, 1-12 months, and >12 months since LT) along with clinical context and symptomatology are important considerations before proceeding with the initial evaluation. Compliance to immunosuppression and drug interactions should be ascertained along with local epidemiology of infections. Essential initial evaluation must include an ultrasound abdomen with Doppler to rule out any structural causes such as biliary or vascular complications apart from focussed laboratory evaluation. Early allograft dysfunction, ischemia reperfusion injury, small-for-size syndrome, biliary leaks, hepatic artery, and portal vein thrombosis are usual culprits in the early post-operative period whereas viral hepatitis (acute or reactivation), opportunistic infections, and recurrence of the primary disease are more frequent in the later period. Graft rejection, biliary strictures, sepsis, and drug induced liver injury remain possible etiologies at all times points after LT. Initial evaluation algorithm must be customized based on history, clinical examination, risk factors, and pattern and severity of deranged LFT. Allograft rejection is a diagnosis of exclusion and requires liver biopsy to confirm and assess severity. Empirical treatment of rejection sans liver biopsy is discouraged.
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Affiliation(s)
- Saurabh Mishra
- Department of Gastroenterology and Hepatology, Paras Health, Sector 22, Panchkula, Haryana 134109, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh 160012, India
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8
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Baba C, Funaki T, Uranaka M, Hashiya M, Ninagawa J, Sakamoto S, Kasahara M, Nagasaka Y, Suzuki Y, Kasuya S. Impact of preoperative bloodstream infection on outcomes of pediatric liver transplant recipients treated for acute liver failure. Transpl Infect Dis 2024; 26:e14200. [PMID: 38010711 DOI: 10.1111/tid.14200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 10/30/2023] [Accepted: 11/12/2023] [Indexed: 11/29/2023]
Abstract
BACKGROUND Acute liver failure (ALF) is a component of multisystem organ failure that causes severe liver dysfunction in patients without underlying chronic liver disease. The patients with ALF are prone to have infections, including bacteremia. However, studies of the infectious impact for post liver transplantation (LT) in pediatric ALF are limited. We aimed to evaluate our current practice for pediatric LT cases of ALF with preoperative bacteremia. METHODS The records of all patients under 18 years old undergoing LT for ALF in our center from November 2005 to December 2021 were collected. They were divided into two groups: those with a preoperative bloodstream infection (BSI) and those without (NBSI). We compared the preoperative status and also reviewed the details of the BSI group. Intraoperative course and postoperative outcomes were also compared. RESULTS There were 19 BSI patients and 66 NBSI patients. One BSI case was detected on the day of LT. This patient had no changes in vital signs and general condition. After evaluation and therapeutic intervention by pediatric infectious disease specialists, LT was performed on the same day. Five cases developed septic shock at the time of detection of BSI. All BSI patients were in stable condition on the operation day with proper interventions. There were no significant differences in mortality and hospital stay between both groups. CONCLUSIONS LT might be able to be performed for pediatric ALF even with positive blood cultures. In addition, appropriate therapeutic intervention by specialists and patient's stable condition before LT are essential.
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Affiliation(s)
- Chiaki Baba
- Division of Anesthesia, Department of Anesthesia and Critical Care, National Center for Child Health and Development, Tokyo, Japan
- Department of Anesthesia, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan
| | - Takanori Funaki
- Division of Infectious Diseases, Department of Medical Subspecialties, National Center for Child Health and Development, Tokyo, Japan
| | - Makoto Uranaka
- Division of Anesthesia, Department of Anesthesia and Critical Care, National Center for Child Health and Development, Tokyo, Japan
| | - Mai Hashiya
- Division of Anesthesia, Department of Anesthesia and Critical Care, National Center for Child Health and Development, Tokyo, Japan
| | - Jun Ninagawa
- Division of Anesthesia, Department of Anesthesia and Critical Care, National Center for Child Health and Development, Tokyo, Japan
| | - Seisuke Sakamoto
- Center for Organ Transplantation, National Center for Child Health and Development, Tokyo, Japan
| | - Mureo Kasahara
- Center for Organ Transplantation, National Center for Child Health and Development, Tokyo, Japan
| | - Yasuko Nagasaka
- Department of Anesthesia, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan
| | - Yasuyuki Suzuki
- Division of Anesthesia, Department of Anesthesia and Critical Care, National Center for Child Health and Development, Tokyo, Japan
- Department of Anesthesia, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan
| | - Shugo Kasuya
- Division of Anesthesia, Department of Anesthesia and Critical Care, National Center for Child Health and Development, Tokyo, Japan
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Agostini C, Buccianti S, Risaliti M, Fortuna L, Tirloni L, Tucci R, Bartolini I, Grazi GL. Complications in Post-Liver Transplant Patients. J Clin Med 2023; 12:6173. [PMID: 37834818 PMCID: PMC10573382 DOI: 10.3390/jcm12196173] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 09/16/2023] [Accepted: 09/22/2023] [Indexed: 10/15/2023] Open
Abstract
Liver transplantation (LT) is the treatment of choice for liver failure and selected cases of malignancies. Transplantation activity has increased over the years, and indications for LT have been widened, leading to organ shortage. To face this condition, a high selection of recipients with prioritizing systems and an enlargement of the donor pool were necessary. Several authors published their case series reporting the results obtained with the use of marginal donors, which seem to have progressively improved over the years. The introduction of in situ and ex situ machine perfusion, although still strongly debated, and better knowledge and treatment of the complications may have a role in achieving better results. With longer survival rates, a significant number of patients will suffer from long-term complications. An extensive review of the literature concerning short- and long-term outcomes is reported trying to highlight the most recent findings. The heterogeneity of the behaviors within the different centers is evident, leading to a difficult comparison of the results and making explicit the need to obtain more consent from experts.
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Affiliation(s)
| | | | | | | | | | | | - Ilenia Bartolini
- Department of Experimental and Clinical Medicine, AOU Careggi, 50134 Florence, Italy; (C.A.); (S.B.); (M.R.); (L.F.); (L.T.); (R.T.); (G.L.G.)
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10
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Khalil A, Quaglia A, Gélat P, Saffari N, Rashidi H, Davidson B. New Developments and Challenges in Liver Transplantation. J Clin Med 2023; 12:5586. [PMID: 37685652 PMCID: PMC10488676 DOI: 10.3390/jcm12175586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 08/15/2023] [Accepted: 08/26/2023] [Indexed: 09/10/2023] Open
Abstract
Liver disease is increasing in incidence and is the third most common cause of premature death in the United Kingdom and fourth in the United States. Liver disease accounts for 2 million deaths globally each year. Three-quarters of patients with liver disease are diagnosed at a late stage, with liver transplantation as the only definitive treatment. Thomas E. Starzl performed the first human liver transplant 60 years ago. It has since become an established treatment for end-stage liver disease, both acute and chronic, including metabolic diseases and primary and, at present piloting, secondary liver cancer. Advances in surgical and anaesthetic techniques, refined indications and contra-indications to transplantation, improved donor selection, immunosuppression and prognostic scoring have allowed the outcomes of liver transplantation to improve year on year. However, there are many limitations to liver transplantation. This review describes the milestones that have occurred in the development of liver transplantation, the current limitations and the ongoing research aimed at overcoming these challenges.
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Affiliation(s)
- Amjad Khalil
- Liver Unit, Wellington Hospital, London NW8 9TA, UK
- Centre for Surgical Innovation, Organ Regeneration and Transplantation, University College London, London NW3 2PS, UK
- Clinical Service of HPB Surgery and Liver Transplantation, Royal Free Hospital, London NW3 2QG, UK
| | - Alberto Quaglia
- Cancer Institute, University College London, London WC1E 6DD, UK
| | - Pierre Gélat
- Division of Surgery and Interventional Science, University College London, London NW3 2PS, UK
| | - Nader Saffari
- Department of Mechanical Engineering, University College London, London WC1E 7JE, UK
| | - Hassan Rashidi
- Institute of Child Health, University College London, London WC1N 1EH, UK;
| | - Brian Davidson
- Liver Unit, Wellington Hospital, London NW8 9TA, UK
- Centre for Surgical Innovation, Organ Regeneration and Transplantation, University College London, London NW3 2PS, UK
- Clinical Service of HPB Surgery and Liver Transplantation, Royal Free Hospital, London NW3 2QG, UK
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11
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Koh B, Tan DJH, Lim WH, Wong JSL, Ng CH, Chan KE, Wang M, Yong WP, Dan YY, Wang LZ, Tan N, Muthiah M, Kow A, Syn NL, Huang DQ, Yau T. Trial watch: immunotherapeutic strategies on the horizon for hepatocellular carcinoma. Oncoimmunology 2023; 12:2214478. [PMID: 37284696 PMCID: PMC10241000 DOI: 10.1080/2162402x.2023.2214478] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 05/10/2023] [Accepted: 05/11/2023] [Indexed: 06/08/2023] Open
Abstract
The use of immune checkpoint inhibitors (ICIs) targeting PD-L1/PD-1 and CTLA-4 has transformed the oncology practice of hepatocellular carcinoma. However, only 25-30% of the patients with advanced HCC treated with atezolizumab-bevacizumab or tremelimumab-durvalumab (STRIDE) respond initially, and mechanistic biomarkers and novel treatment strategies are urgently needed for patients who present with or acquire resistance to first-line ICI-based therapies. The recent approval of the STRIDE regimen has also engendered new questions, such as patient selection factors (e.g. portal hypertension and history of variceal bleed) and biomarkers, and the optimal combination and sequencing of ICI-based regimens. Triumphs in the setting of advanced HCC have also galvanized considerable interest in the broader application of ICIs to early- and intermediate-stage diseases, including clinical combination of ICIs with locoregional therapies. Among these clinical contexts, the role of ICIs in liver transplantation - which is a potentially curative strategy unique to HCC management - as a bridge to liver transplant in potential candidates or in the setting of post-transplant recurrence, warrants investigation in view of the notable theoretical risk of allograft rejection. In this review, we summarize and chart the landscape of seminal immuno-oncology trials in HCC and envision future clinical developments.
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Affiliation(s)
- Benjamin Koh
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Jeffrey S L Wong
- Department of Medicine, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, Special Administrative Region, China
- State Key Laboratory for Liver Disease, University of Hong Kong, Hong Kong, Special Administrative Region, China
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Kai En Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Meng Wang
- Division of Advanced Internal Medicine, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Wei Peng Yong
- Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore
- Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
| | - Yock Young Dan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Louis Z Wang
- SingHealth Internal Medicine Residency Programme, Singapore General Hospital, Singapore, Singapore
| | - Nigel Tan
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, University Surgical Cluster, Singapore, Singapore
| | - Mark Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- Division of Advanced Internal Medicine, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Alfred Kow
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, University Surgical Cluster, Singapore, Singapore
| | - Nicholas L. Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
- Department of Pathology, National University Hospital, Singapore, Singapore
| | - Daniel Q. Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- Division of Advanced Internal Medicine, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Thomas Yau
- Department of Medicine, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, Special Administrative Region, China
- State Key Laboratory for Liver Disease, University of Hong Kong, Hong Kong, Special Administrative Region, China
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The Role of Microbiota in Liver Transplantation and Liver Transplantation-Related Biliary Complications. Int J Mol Sci 2023; 24:ijms24054841. [PMID: 36902269 PMCID: PMC10003075 DOI: 10.3390/ijms24054841] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 02/22/2023] [Accepted: 02/28/2023] [Indexed: 03/06/2023] Open
Abstract
Liver transplantation as a treatment option for end-stage liver diseases is associated with a relevant risk for complications. On the one hand, immunological factors and associated chronic graft rejection are major causes of morbidity and carry an increased risk of mortality due to liver graft failure. On the other hand, infectious complications have a major impact on patient outcomes. In addition, abdominal or pulmonary infections, and biliary complications, including cholangitis, are common complications in patients after liver transplantation and can also be associated with a risk for mortality. Thereby, these patients already suffer from gut dysbiosis at the time of liver transplantation due to their severe underlying disease, causing end-stage liver failure. Despite an impaired gut-liver axis, repeated antibiotic therapies can cause major changes in the gut microbiome. Due to repeated biliary interventions, the biliary tract is often colonized by several bacteria with a high risk for multi-drug resistant germs causing local and systemic infections before and after liver transplantation. Growing evidence about the role of gut microbiota in the perioperative course and their impact on patient outcomes in liver transplantation is available. However, data about biliary microbiota and their impact on infectious and biliary complications are still sparse. In this comprehensive review, we compile the current evidence for the role of microbiome research in liver transplantation with a focus on biliary complications and infections due to multi-drug resistant germs.
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13
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Ruck JM, King EA, Chu NM, Segev DL, McAdams-DeMarco M. Cognitive Dysfunction in Liver Disease and Its Implications for Transplant Candidates. CURRENT TRANSPLANTATION REPORTS 2023. [DOI: 10.1007/s40472-023-00390-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
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14
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Banc-Husu AM, Moulton EA, Shiau H, Gutierrez Sanchez LH, Desai MS, Cerminara D, Munoz FM, Buffaloe LM, Valencia-Deray KG, Galvan NTN, Bhatnagar J, Estetter L, Rassaei N, Reagan-Steiner S, Wicker J, Dunn JJ, Allen CE, Patel KR, Harpavat S, Goss JA, Leung DH. Acute liver failure and unique challenges of pediatric liver transplantation amidst a worldwide cluster of adenovirus-associated hepatitis. Am J Transplant 2023; 23:93-100. [PMID: 36695626 DOI: 10.1016/j.ajt.2022.10.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 10/13/2022] [Accepted: 10/15/2022] [Indexed: 01/13/2023]
Abstract
Investigation into a recent cluster of acute hepatitis in children from the southeastern United States identified human adenovirus (HAdV) DNAemia in all 9 cases. Molecular genotyping in 5 of 9 (56%) children identified HAdV type 41 in all cases (100%). Importantly, 2 children from this cluster progressed rapidly to pediatric acute liver failure (PALF) and required liver transplantation. HAdV type 41, a known cause of self-limited gastroenteritis, has not previously been associated with severe cholestatic hepatitis and liver failure in healthy children. Adenovirus polymerase chain reaction assay and sequencing of amplicons performed on DNA extracted from formalin-fixed, paraffin-embedded liver tissue also identified adenovirus species F (HAdV type 40 or 41) in these 2 children with PALF. Transplant considerations and successful liver transplantation in such situations remain scarce. In this report, we describe the clinical course, laboratory results, liver pathology, and treatment of 2 children with PALF associated with HAdV type 41, one of whom developed secondary hemophagocytic lymphohistiocytosis. Their successful posttransplant outcomes demonstrate the importance of early multidisciplinary medical management and the feasibility of liver transplantation in some children with PALF and HAdV DNAemia.
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Affiliation(s)
- Anna M Banc-Husu
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - Elizabeth A Moulton
- Division of Infectious Disease, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - Henry Shiau
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA; Children's of Alabama, Birmingham, Alabama, USA
| | - Luz Helena Gutierrez Sanchez
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA; Children's of Alabama, Birmingham, Alabama, USA
| | - Moreshwar S Desai
- Pediatric Critical Care and Liver ICU, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - Dana Cerminara
- Department of Pharmacy, Texas Children's Hospital, Houston, Texas, USA
| | - Flor M Munoz
- Division of Infectious Disease, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - Leanne M Buffaloe
- Division of Infectious Disease, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - Kristen G Valencia-Deray
- Division of Infectious Disease, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - N Thao N Galvan
- Division of Abdominal Transplantation and Hepatobiliary Surgery, Department of Surgery, Baylor College of Medicine, Houston, Texas, USA
| | - Julu Bhatnagar
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Lindsey Estetter
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Negar Rassaei
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Sarah Reagan-Steiner
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Jason Wicker
- Children's of Alabama, Birmingham, Alabama, USA; Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - James J Dunn
- Department of Pathology and Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - Carl E Allen
- Division of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - Kalyani R Patel
- Department of Pathology and Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - Sanjiv Harpavat
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - John A Goss
- Division of Abdominal Transplantation and Hepatobiliary Surgery, Department of Surgery, Baylor College of Medicine, Houston, Texas, USA
| | - Daniel H Leung
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA.
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Ferri JVV, Dick SM, Grezzana-Filho TDJM, Feier FH, Prediger L, Lazzaretti GS, Kruel CRP, Corso CO, Cavazzola LT, Chedid MF. EARLY INCISIONAL HERNIA AFTER LIVER TRANSPLANTATION: RISK FACTORS AND HERNIA REPAIR RESULTS. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2022; 35:e1698. [PMID: 36350959 PMCID: PMC9645553 DOI: 10.1590/0102-672020220002e1698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 08/18/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND Liver transplantation is a complex and valuable therapy. However, complications that burden postoperative quality of life, such as incisional hernia, are to be better elucidated, such as risk factors and prophylactic measures. AIM This study aimed to define the rate of incisional hernia in patients who underwent liver transplantation in a population in southern Brazil and to assess the related risk factors in order to establish measures for prior optimization and specific prophylactic care in the future. METHODS Patients undergoing adult Liver transplantation from January 2004 to November 2020 were retrospectively analyzed, assessing demographic features, surgical outcomes, and predisposing factors. RESULTS Among 261 liver transplantation patients included, incisional hernia was diagnosed in 71 (27.2%). Of the 71 incisional hernia patients, 28 (39.4%) developed IH during the first post-transplant. Majority of the patients were male (52/71, 73.2%); of the 71 patients, 52 had hepatitis C virus (HCV) and 33 (46.5%) had hepatocellular carcinoma (HCC). Male gender (p=0.044), diabetes mellitus (p=0.008), and acute cellular rejection (p<0.001) were risk factors for IH. In all, 28 (39.4%) patients were submitted for hernia repair with mesh, with a recurrence rate of 17.8%. CONCLUSION Incisional hernia after liver transplantation is a relatively common problem associated with male gender, diabetes, and acute cellular rejection. This is a problem that should not be trivialized in view of the complexity of liver transplantation, as it can lead to a reduction in quality of life as well as jeopardize late liver transplantation results and lead to incarceration and strangulation.
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Affiliation(s)
| | - Sofia Michele Dick
- University Hospital of Porto Alegre, Surgery Unit – Porto Alegre (RS), Brazil
| | | | - Flávia Heinz Feier
- University Hospital of Porto Alegre, Surgery Unit – Porto Alegre (RS), Brazil
| | - Lucas Prediger
- Federal University of Rio Grande do Sul, Faculty of Medicine – Porto Alegre (RS), Brazil
| | | | | | - Carlos Otavio Corso
- University Hospital of Porto Alegre, Surgery Unit – Porto Alegre (RS), Brazil
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Motomura T, Faccioli LA, Diaz-Aragon R, Kocas-Kilicarslan ZN, Haep N, Florentino RM, Amirneni S, Cetin Z, Peri BS, Morita K, Ostrowska A, Takeishi K, Soto-Gutierrez A, Tafaleng EN. From a Single Cell to a Whole Human Liver: Disease Modeling and Transplantation. Semin Liver Dis 2022; 42:413-422. [PMID: 36044927 PMCID: PMC9718640 DOI: 10.1055/a-1934-5404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Although the underlying cause may vary across countries and demographic groups, liver disease is a major cause of morbidity and mortality globally. Orthotopic liver transplantation is the only definitive treatment for liver failure but is limited by the lack of donor livers. The development of drugs that prevent the progression of liver disease and the generation of alternative liver constructs for transplantation could help alleviate the burden of liver disease. Bioengineered livers containing human induced pluripotent stem cell (iPSC)-derived liver cells are being utilized to study liver disease and to identify and test potential therapeutics. Moreover, bioengineered livers containing pig hepatocytes and endothelial cells have been shown to function and survive after transplantation into pig models of liver failure, providing preclinical evidence toward future clinical applications. Finally, bioengineered livers containing human iPSC-derived liver cells have been shown to function and survive after transplantation in rodents but require considerable optimization and testing prior to clinical use. In conclusion, bioengineered livers have emerged as a suitable tool for modeling liver diseases and as a promising alternative graft for clinical transplantation. The integration of novel technologies and techniques for the assembly and analysis of bioengineered livers will undoubtedly expand future applications in basic research and clinical transplantation.
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Affiliation(s)
- Takashi Motomura
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Lanuza A.P. Faccioli
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Ricardo Diaz-Aragon
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | | | - Nils Haep
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Rodrigo M. Florentino
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Sriram Amirneni
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Zeliha Cetin
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Bhaavna S. Peri
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Kazutoyo Morita
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Alina Ostrowska
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
- Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Kazuki Takeishi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Alejandro Soto-Gutierrez
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
- Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
- McGowan Institute for Regenerative Medicine, Pittsburgh, Pennsylvania
| | - Edgar N. Tafaleng
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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High visceral adipose tissue area is independently associated with early allograft dysfunction in liver transplantation recipients: a propensity score analysis. Insights Imaging 2022; 13:165. [PMID: 36219263 DOI: 10.1186/s13244-022-01302-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 09/20/2022] [Indexed: 11/10/2022] Open
Abstract
OBJECTIVES To evaluate the association between adipose tissue distribution and early allograft dysfunction (EAD) in liver transplantation (LT) recipients. METHODS A total of 175 patients who received LT from April 2015 to September 2020 were enrolled in this retrospective study. The areas of abdominal adipose tissue and skeletal muscle of all patients were measured based on the preoperative CT images. The appropriate statistical methods including the propensity score-matched (PSM) analysis were performed to identify the association between adipose tissue distribution and EAD. RESULTS Of 175 LT recipients, 55 patients (31.4%) finally developed EAD. The multivariate logistic analysis revealed that preoperative serum albumin (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.17-0.70), platelet-lymphocyte ratio (OR 2.35, 95% CI 1.18-4.79), and visceral adipose tissue (VAT) area (OR 3.17, 95% CI 1.56-6.43) were independent associated with EAD. After PSM analysis, VAT area was still significantly associated with EAD (OR 3.95, 95% CI 1.16-13.51). In survival analysis, no significant difference was identified in one-year graft failure (log-rank: p = 0.487), and conversely result was identified in overall survival (OS) (log-rank: p = 0.012; hazard ratio (HR) 4.10, 95% CI 1.27-13.16). CONCLUSIONS LT recipients with high VAT area have higher risk for the occurrence of EAD, and high VAT area might have certain clinical value for predicting the poor OS of patients. For LT candidates with large amount of VAT, the clinicians can take clinical interventions by suggesting physical and nutritional treatments to improve outcomes after LT.
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18
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Ionescu VA, Diaconu CC, Bungau S, Jinga V, Gheorghe G. Current Approaches in the Allocation of Liver Transplantation. J Pers Med 2022; 12:jpm12101661. [PMID: 36294801 PMCID: PMC9605642 DOI: 10.3390/jpm12101661] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 09/26/2022] [Accepted: 10/04/2022] [Indexed: 11/07/2022] Open
Abstract
In recent decades, important advances have been made in the field of liver transplantation. One of the major problems remaining in this area is the small number of donors. Thus, recent data bring multiple updates of the indications and contraindications of this therapeutic method. The main goal is to increase the number of patients who can benefit from liver transplantation, a therapeutic method that can improve life expectancy and the quality of life of patients with end-stage liver disease. Another goal in the management of these patients is represented by the optimal care of those on the waiting list during that period. A multidisciplinary team approach is necessary to obtain the best results for both the donor and the recipient.
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Affiliation(s)
- Vlad Alexandru Ionescu
- “Prof. Dr. Theodor Burghele” Clinical Hospital, University of Medicine and Pharmacy Carol Davila, 050474 Bucharest, Romania
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Camelia Cristina Diaconu
- “Prof. Dr. Theodor Burghele” Clinical Hospital, University of Medicine and Pharmacy Carol Davila, 050474 Bucharest, Romania
- Department of Internal Medicine, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
- Medical Sciences Section, Academy of Romanian Scientists, 050085 Bucharest, Romania
- Correspondence: (C.C.D.); (S.B.); Tel.: +40-726-377-300 (C.C.D.)
| | - Simona Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania
- Correspondence: (C.C.D.); (S.B.); Tel.: +40-726-377-300 (C.C.D.)
| | - Viorel Jinga
- “Prof. Dr. Theodor Burghele” Clinical Hospital, University of Medicine and Pharmacy Carol Davila, 050474 Bucharest, Romania
- Medical Sciences Section, Academy of Romanian Scientists, 050085 Bucharest, Romania
- Department of Urology, “Prof. Dr. Theodor Burghele” Hospital, 050653 Bucharest, Romania
| | - Gina Gheorghe
- “Prof. Dr. Theodor Burghele” Clinical Hospital, University of Medicine and Pharmacy Carol Davila, 050474 Bucharest, Romania
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
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Flores-Calderón J, Cisneros-Garza LE, Chávez-Barrera JA, Vázquez-Frias R, Reynoso-Zarzosa FA, Martínez-Bejarano DL, Consuelo-Sánchez A, Reyes-Apodaca M, Zárate-Mondragón FE, Sánchez-Soto MP, Alcántara-García RI, González-Ortiz B, Ledesma-Ramírez S, Espinosa-Saavedra D, Cura-Esquivel IA, Macías-Flores J, Hinojosa-Lezama JM, Hernández-Chávez E, Zárate-Guerrero JR, Gómez-Navarro G, Bilbao-Chávez LP, Sosa-Arce M, Flores-Fong LE, Lona-Reyes JC, Estrada-Arce EV, Aguila-Cano R. Consensus on the management of complications of cirrhosis of the liver in pediatrics. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2022; 87:462-485. [PMID: 35810090 DOI: 10.1016/j.rgmxen.2022.06.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 03/08/2022] [Indexed: 12/07/2022]
Abstract
The Asociación Mexicana de Hepatología A.C. carried out the Consensus on the Management of Complications of Cirrhosis of the Liver in Pediatrics to provide physicians with useful information for treating said complications. A group of pediatric gastroenterologists and experts in nutrition, nephrology, and infectious diseases participated and reviewed the medical literature. The Delphi method was applied to obtain the level of agreement on the statements that were formulated. The statements were sent to the participants to be analyzed and voted upon, after which they were discussed in virtual sessions, and the final versions were produced. The aim of the consensus results was to issue indications for the management of pediatric patients with liver cirrhosis, to prevent or control complications.
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Affiliation(s)
- J Flores-Calderón
- UMAE Hospital de Pediatría, CMN XXI Dr. Silvestre Frenk Freund IMSS, Cd, México, Mexico.
| | | | - J A Chávez-Barrera
- UMAE Hospital General CMN La Raza, Dr. Gaudencio González Garza IMSS, Cd, México, Mexico
| | | | | | | | | | | | | | - M P Sánchez-Soto
- Hospital de Especialidades del Niño y la mujer de Querétaro Dr. Felipe Núñez Lara, Querétaro, Mexico
| | | | - B González-Ortiz
- UMAE Hospital de Pediatría, CMN XXI Dr. Silvestre Frenk Freund IMSS, Cd, México, Mexico
| | - S Ledesma-Ramírez
- UMAE Hospital de Pediatría, CMN XXI Dr. Silvestre Frenk Freund IMSS, Cd, México, Mexico
| | - D Espinosa-Saavedra
- UMAE Hospital de Pediatría, CMN XXI Dr. Silvestre Frenk Freund IMSS, Cd, México, Mexico
| | | | - J Macías-Flores
- Hospital Infantil de Especialidades de Chihuahua, Chihuahua, Mexico
| | | | - E Hernández-Chávez
- UMAE Hospital de Pediatría Centro Médico de Occidente, IMSS, Guadalajara, Mexico
| | - J R Zárate-Guerrero
- UMAE Hospital de Pediatría Centro Médico de Occidente, IMSS, Guadalajara, Mexico
| | - G Gómez-Navarro
- UMAE Hospital de Pediatría Centro Médico de Occidente, IMSS, Guadalajara, Mexico
| | - L P Bilbao-Chávez
- UMAE Hospital General CMN La Raza, Dr. Gaudencio González Garza IMSS, Cd, México, Mexico
| | - M Sosa-Arce
- UMAE Hospital General CMN La Raza, Dr. Gaudencio González Garza IMSS, Cd, México, Mexico
| | - L E Flores-Fong
- Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Guadalajara, Mexico
| | - J C Lona-Reyes
- Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Guadalajara, Mexico
| | - E V Estrada-Arce
- Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Guadalajara, Mexico
| | - R Aguila-Cano
- Nuevo Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", Guadalajara, Mexico
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20
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Salah M, Montasser IF, El Gendy HA, Korraa AA, Elewa GM, Dabbous H, Mahfouz HR, Abdelrahman M, Goda MH, Bahaa El-Din MM, El-Meteini M, Labib HA. Intensive care unit readmission in adult Egyptian patients undergoing living donor liver transplant: A single-centre retrospective cohort study. World J Hepatol 2022; 14:1150-1161. [PMID: 35978667 PMCID: PMC9258246 DOI: 10.4254/wjh.v14.i6.1150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 04/01/2022] [Accepted: 06/03/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Patients who undergo living donor liver transplantation (LDLT) may suffer complications that require intensive care unit (ICU) readmission. AIM To identify the incidence, causes, and outcomes of ICU readmission after LDLT. METHODS A retrospective cohort study was conducted on patients who underwent LDLT. The collected data included patient demographics, preoperative characteristics, intraoperative details; postoperative stay, complications, causes of ICU readmission, and outcomes. Patients were divided into two groups according to ICU readmission after hospital discharge. Risk factors for ICU readmission were identified in univariate and multivariate analyses. RESULTS The present study included 299 patients. Thirty-one (10.4%) patients were readmitted to the ICU after discharge. Patients who were readmitted to the ICU were older in age (53.0 ± 5.1 vs 49.4 ± 8.8, P = 0.001) and had a significantly higher percentage of women (29% vs 13.4%, P = 0.032), diabetics (41.9% vs 24.6%, P = 0.039), hypertensives (22.6% vs 6.3%, P = 0.006), and renal (6.5% vs 0%, P = 0.010) patients as well as a significantly longer initial ICU stay (6 vs 4 d, respectively, P < 0.001). Logistic regression analysis revealed that significant independent risk factors for ICU readmission included recipient age (OR = 1.048, 95%CI = 1.005-1.094, P = 0.030) and length of initial hospital stay (OR = 0.836, 95%CI = 0.789-0.885, P < 0.001). CONCLUSION The identification of high-risk patients (older age and shorter initial hospital stay) before ICU discharge may help provide optimal care and tailor follow-up to reduce the rate of ICU readmission.
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Affiliation(s)
- Manar Salah
- Department of Tropical Medicine, Ain Shams Center for Organ Transplantation, Ain Shams University, Cairo 11566, Egypt
| | - Iman Fawzy Montasser
- Department of Tropical Medicine, Ain Shams Center for Organ Transplantation, Ain Shams University, Cairo 11566, Egypt.
| | - Hanaa A El Gendy
- Department of Anaesthesia and Critical Care, Ain Shams Centre for Organ Transplantation, Ain Shams University, Cairo 11566, Egypt
| | - Alaa A Korraa
- Department of Anaesthesia and Critical Care, Ain Shams Centre for Organ Transplantation, Ain Shams University, Cairo 11566, Egypt
| | - Gamal M Elewa
- Department of Anaesthesia and Critical Care, Ain Shams Centre for Organ Transplantation, Ain Shams University, Cairo 11566, Egypt
| | - Hany Dabbous
- Department of Tropical Medicine, Ain Shams Center for Organ Transplantation, Ain Shams University, Cairo 11566, Egypt
| | - Hossam R Mahfouz
- Department of Anaesthesia and Critical Care, Ain Shams Centre for Organ Transplantation, Ain Shams University, Cairo 11566, Egypt
| | - Mostafa Abdelrahman
- Department of General Surgery and Liver Transplantation, Ain Shams Centre for Organ Transplantation, Ain Shams University, Cairo 11566, Egypt
| | - Mohammed Hisham Goda
- Department of General Surgery and Liver Transplantation, Ain Shams Centre for Organ Transplantation, Ain Shams University, Cairo 11566, Egypt
| | - Mohamed Mohamed Bahaa El-Din
- Department of General Surgery and Liver Transplantation, Ain Shams Centre for Organ Transplantation, Ain Shams University, Cairo 11566, Egypt
| | - Mahmoud El-Meteini
- Department of General Surgery and Liver Transplantation, Ain Shams Centre for Organ Transplantation, Ain Shams University, Cairo 11566, Egypt
| | - Heba A Labib
- Department of Anaesthesia and Critical Care, Ain Shams Centre for Organ Transplantation, Ain Shams University, Cairo 11566, Egypt
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21
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Urlik M, Latos M, Stącel T, Wystrychowski W, Joanna M, Nęcki M, Antończyk R, Badura J, Horynecka Z, Sekta S, Król B, Gawęda M, Pandel A, Zembala M, Ochman M, Król R. First in Poland Simultaneous Liver-Lung Transplantation With Liver-First Approach for Recipient Due to Cystic Fibrosis: A Case Report. Transplant Proc 2022; 54:1171-1176. [PMID: 35597673 DOI: 10.1016/j.transproceed.2022.02.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 02/18/2022] [Indexed: 10/18/2022]
Abstract
Cystic fibrosis is an autosomal progressive disease affecting the lung, pancreas, and liver. Some patients develop end-stage respiratory and liver failure. For such patients, combined lung-liver transplantation remains the only therapeutic option. In this article we present the first simultaneous lung-liver transplantation in Poland, as well as in Central and Eastern Europe, with detailed clinical history, surgical aspects, and postoperative course.
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Affiliation(s)
- Maciej Urlik
- Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Silesian Center for Heart Diseases in Zabrze, Medical University of Silesia, Katowice, Poland.
| | - Magdalena Latos
- Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Silesian Center for Heart Diseases in Zabrze, Medical University of Silesia, Katowice, Poland.
| | - Tomasz Stącel
- Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Silesian Center for Heart Diseases in Zabrze, Medical University of Silesia, Katowice, Poland.
| | - Wojciech Wystrychowski
- Department of General, Vascular and Transplant Surgery, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
| | - Musialik Joanna
- Department of General, Vascular and Transplant Surgery, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
| | - Mirosław Nęcki
- Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Silesian Center for Heart Diseases in Zabrze, Medical University of Silesia, Katowice, Poland.
| | - Remigiusz Antończyk
- Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Silesian Center for Heart Diseases in Zabrze, Medical University of Silesia, Katowice, Poland.
| | - Joanna Badura
- Department of General, Vascular and Transplant Surgery, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
| | - Zuzanna Horynecka
- Department of General, Vascular and Transplant Surgery, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
| | - Sylwia Sekta
- Department of General, Vascular and Transplant Surgery, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
| | - Bogumiła Król
- Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Silesian Center for Heart Diseases in Zabrze, Medical University of Silesia, Katowice, Poland.
| | - Martyna Gawęda
- Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Silesian Center for Heart Diseases in Zabrze, Medical University of Silesia, Katowice, Poland.
| | - Anastazja Pandel
- Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Silesian Center for Heart Diseases in Zabrze, Medical University of Silesia, Katowice, Poland.
| | - Marian Zembala
- Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Silesian Center for Heart Diseases in Zabrze, Medical University of Silesia, Katowice, Poland.
| | - Marek Ochman
- Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Silesian Center for Heart Diseases in Zabrze, Medical University of Silesia, Katowice, Poland.
| | - Robert Król
- Department of General, Vascular and Transplant Surgery, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
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22
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Hosaagrahara Ramakrishna S, Kasala MB, Perumal K, Malleeswaran S, Patcha RV, Varghese J, Sathiyasekaran M, Reddy MS. When Push Comes to Shove! Emergency ABO-Incompatible Pediatric Living Donor Liver Transplant for Acute Wilson's Disease. J Clin Exp Hepatol 2022; 12:658-663. [PMID: 35535085 PMCID: PMC9077158 DOI: 10.1016/j.jceh.2021.08.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 08/09/2021] [Indexed: 12/12/2022] Open
Abstract
ABO-incompatible living donor liver transplantation (ABOi-LDLT) is on the rise as a viable option in countries with limited access to deceased donor grafts. While reported outcomes of ABOi-LT in children are similar to ABO- Compatible liver transplant (ABOc-LT), most children beyond 1-2 years of age will need desensitization to overcome the immunological barrier of incompatible blood groups. The current standard protocol for desensitization is Rituximab that targets B lymphocytes and is given 2-3 weeks prior to LT. However, this timeline may not be feasible in children requiring emergency LT for acute liver failure (ALF) or acute-on-chronic liver failure (ACLF). In this emergency situation of ABOi-LT, a safe multipronged approach may be an acceptable alternative solution. We report a child with acute Wilson's disease with rapidly deteriorating liver function who underwent a successful ABOi-LDLT using a rapid desensitization protocol.
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Key Words
- ABOc-LT, ABO-compatible liver transplantation (ABOi-LDLT)
- ABOi-LDLT, ABO-incompatible living donor liver transplantation
- ACLF, Acute-on-chronic liver failure
- ALF, Acute liver failure
- AMR, Antibody-mediated rejection
- CMV, Cytomegalovirus
- CSF, Cerebrospinal fluid
- GRWR, Graft-to-recipient weight ratio
- LDLT, Living donor liver transplantation
- LT, Liver transplant
- MMF, Mycophenolate mofetil
- PVT, Portal vein thrombosis
- Rituximab
- acute Wilson’s disease
- acute-on-chronic liver disease
- emergency ABOi-LDLT
- living donor liver transplantation
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Affiliation(s)
| | - Mohan Babu Kasala
- Department of Pediatric Intensive Care, Gleneagles Global Health City, Perumbakkam, Chennai, India
| | - Karnan Perumal
- Department of Pediatric Intensive Care, Gleneagles Global Health City, Perumbakkam, Chennai, India
| | - Selvakumar Malleeswaran
- Liver Anesthesia and Critical Care, Gleneagles Global Health City, Perumbakkam, Chennai, India
| | - Rajanikanth V Patcha
- Department of Liver Transplant and Hepatopancreaticobiliary Surgery, Gleneagles Global Health City, Perumbakkam, Chennai, India
| | - Joy Varghese
- Department of Hepatology and Liver Transplant, Gleneagles Global Health City, Perumbakkam, Chennai, India
| | - Malathy Sathiyasekaran
- Senior Pediatric Gastroenterologist, MGM, Rainbow and Kanchi Kamakoti CHILDs Trust Hospitals, Chennai, India
| | - Mettu Srinivas Reddy
- Department of Liver Transplant and Hepatopancreaticobiliary Surgery, Gleneagles Global Health City, Perumbakkam, Chennai, India
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Expert consensus on perioperative management of liver transplantation in adults with acute-on-chronic liver failure. LIVER RESEARCH 2021; 5:37-44. [PMID: 39959341 PMCID: PMC11791809 DOI: 10.1016/j.livres.2021.03.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 03/17/2021] [Indexed: 12/13/2022]
Abstract
Acute-on-chronic liver failure (ACLF) is a syndrome in which acute liver failure with extrahepatic organ failure occurs on chronic liver disease. Recently, liver transplantation is the only effective treatment for ACLF. There is still room for discussion on the optimal surgery timing for ACLF, perioperative infection prevention and control, and maintenance of nutrition and organ function. The Transplantation Immunology Committee of Branch of Organ Transplantation Physician of Chinese Medical Doctor Association and Enhanced Recovery of Liver Transplantation Group of Enhanced Recovery after Surgery Committee of Chinese Research Hospital Association invited relevant experts to discuss the perioperative management of ACLF liver transplantation in areas including surgery timing, organ protection, nutritional support, infection prevention and control, rehabilitation exercises, regulation of the internal environment, etc. An expert consensus was developed as reference for clinicians.
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24
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Tafaleng EN, Malizio MR, Fox IJ, Soto-Gutierrez A. Synthetic human livers for modeling metabolic diseases. Curr Opin Gastroenterol 2021; 37:224-230. [PMID: 33769378 PMCID: PMC8223234 DOI: 10.1097/mog.0000000000000726] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE OF REVIEW In this review, we will explore recent advances in human induced pluripotent stem cell (iPSC)-based modeling of metabolic liver disease and biofabrication of synthetic human liver tissue while also discussing the emerging concept of synthetic biology to generate more physiologically relevant liver disease models. RECENT FINDING iPSC-based platforms have facilitated the study of underlying cellular mechanisms and potential therapeutic strategies for a number of metabolic liver diseases. Concurrently, rapid progress in biofabrication and gene editing technologies have led to the generation of human hepatic tissue that more closely mimic the complexity of the liver. SUMMARY iPSC-based liver tissue is rapidly becoming available for modeling liver physiology due to its ability to recapitulate the complex three-dimensional architecture of the liver and recapitulate interactions between the different cell types and their surroundings. These mini livers have also been used to recapitulate liver disease pathways using the tools of synthetic biology, such as gene editing, to control gene circuits. Further development in this field will undoubtedly bolster future investigations not only in disease modeling and basic research, but also in personalized medicine and autologous transplantation.
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Affiliation(s)
- Edgar N. Tafaleng
- Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania, USA
| | - Michelle R. Malizio
- Department of Pathology, University of Pittsburgh School of Medicine, Pennsylvania, USA
| | - Ira J. Fox
- Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania, USA
- Pittsburgh Liver Research Center, University of Pittsburgh, Pennsylvania, USA
- McGowan Institute for Regenerative Medicine, Pittsburgh, Pennsylvania, USA
| | - Alejandro Soto-Gutierrez
- Department of Pathology, University of Pittsburgh School of Medicine, Pennsylvania, USA
- Pittsburgh Liver Research Center, University of Pittsburgh, Pennsylvania, USA
- McGowan Institute for Regenerative Medicine, Pittsburgh, Pennsylvania, USA
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25
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Kaur N, Emamaullee J, Lian T, Lo M, Ender P, Kahn J, Sher L. Impact of Morbid Obesity on Liver Transplant Candidacy and Outcomes: National and Regional Trends. Transplantation 2021; 105:1052-1060. [PMID: 33741845 DOI: 10.1097/tp.0000000000003404] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Body mass index (BMI) limits for liver transplant (LT) candidacy are controversial. In this study, we evaluate waitlist and post-LT outcomes, and prognostic factors and examine regional patterns of LT waitlist registration in patients with BMI ≥40 versus BMI 18-39. METHODS United Network for Organ Sharing (UNOS) data were analyzed to assess waitlist dropout, post-LT survival, and prognostic factors for patient survival. The distribution of waitlisted patients with BMI ≥40 was compared with the Centers for Disease Control Behavioral Risk Factors Surveillance System data to explore the rates of morbid obesity in the general population of each UNOS region. RESULTS Post-LT outcomes demonstrate a small but significantly lower 1- and 3-y overall survival for patients with BMI ≥45. Risk factors for post-LT mortality for patients with BMI ≥40 included age >60 y, prior surgery, and diabetes on multivariable analysis. Model for End-Stage Liver Disease >30 was significant on univariable analysis only, likely due to the limited number of patients with BMI ≥40; however, median Model for End-Stage Liver Disease scores in this BMI group were higher than those in patients with lower BMI across all UNOS regions. Patients with BMI ≥40 had a higher waitlist dropout in 4 regions. Comparison with BRFSS data illustrated that the proportion of waitlisted patients with BMI ≥40 was significantly lower than the observed rates of morbid obesity in the general population in 3 regions. CONCLUSIONS While BMI ≥45 is associated with modestly lower patient survival, careful selection may equalize these numbers.
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Affiliation(s)
- Navpreet Kaur
- Department of Surgery, University of Southern California, Los Angeles, CA
- Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Juliet Emamaullee
- Department of Surgery, University of Southern California, Los Angeles, CA
- Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Tiffany Lian
- Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Mary Lo
- Department of Preventive Medicine, University of Southern California, Los Angeles, CA
| | - Philip Ender
- Statistical Consulting Group, University of California-Los Angeles, Los Angeles, CA
| | - Jeffrey Kahn
- Keck School of Medicine, University of Southern California, Los Angeles, CA
- Department of Medicine, University of Southern California, Los Angeles, CA
| | - Linda Sher
- Department of Surgery, University of Southern California, Los Angeles, CA
- Keck School of Medicine, University of Southern California, Los Angeles, CA
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26
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Fan G, Zhang C, Wei X, Wei R, Qi Z, Chen K, Cai X, Xu L, Tang L, Zhou J, Zhang Z, Lin Z, Xie H, Zheng S, Fan W, Xu X. NEAT1/hsa-miR-372-3p axis participates in rapamycin-induced lipid metabolic disorder. Free Radic Biol Med 2021; 167:1-11. [PMID: 33705959 DOI: 10.1016/j.freeradbiomed.2021.02.033] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 02/20/2021] [Accepted: 02/24/2021] [Indexed: 12/11/2022]
Abstract
Rapamycin is a crucial immunosuppressive regimen for patients that have undergone liver transplantation (LT). However, one of the major side effects of rapamycin include metabolic disorders such as dyslipidemia, and the mechanism remains unknown. This study aims to explore the biomolecules that are responsible for rapamycin-induced dyslipidemia and the control strategies that can reverse the lipid metabolism disorder. In this study, data collected from LT patients, cell and mouse models treated with rapamycin were analyzed. Results showed an increase of triglycerides (TGs) induced by rapamycin. MicroRNAs (miRNAs) play important roles in many vital biological processes including TG metabolism. hsa-miR-372-3p was filtered using RNA sequencing and identified as a key regulator in rapamycin-induced TGs accumulation. Using bioinformatics and experimental analyses, target genes of hsa-miR-372-3p were predicted. These genes were alkylglycerone phosphate synthase (AGPS) and apolipoprotein C4 (APOC4), which are reported to be involved in TG metabolism. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was also identified as an upstream regulatory factor of hsa-miR-372-3p. From the results of this study, NEAT1/hsa-miR-372-3p/AGPS/APOC4 axis plays a vital role in rapamycin-disruption of lipid homeostasis. Therefore, targeting this axis is a potential therapeutic target combating rapamycin-induced dyslipidemia after LT.
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Affiliation(s)
- Guanghan Fan
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Chenzhi Zhang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Xuyong Wei
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Rongli Wei
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Zhetuo Qi
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Kangchen Chen
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Xuechun Cai
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Li Xu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Linsong Tang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Junbin Zhou
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Zhensheng Zhang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Zuyuan Lin
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Haiyang Xie
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Shusen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China; Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou, 310000, China
| | - Weimin Fan
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China; Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China.
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27
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González IA, Hartley CP, Nalbantoglu ILK. Recurrent Autoimmune Hepatitis and De Novo Autoimmune Hepatitis in the Liver Allograft. Am J Clin Pathol 2021; 155:435-445. [PMID: 33252121 DOI: 10.1093/ajcp/aqaa147] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES Autoimmune hepatitis (AIH) is a form of severe hepatitis that can recur after orthotopic liver transplant (OLT). Presentation of AIH in patients with OLT who do not have a history of AIH is called de novo AIH (DNAIH). We evaluated the clinicopathologic characteristics of AIH and DNAIH. METHODS Clinicopathologic and outcome measures of 11 patients with recurrent AIH (RAIH) and 22 with DNAIH identified between 2000 and 2017 were compared. RESULTS Both cohorts showed female predominance. The mean clinical follow-up was 13 and 7.8 years in the in the RAIH and DNAIH groups, respectively (P = .1). Moderate portal inflammation was more common in patients with RAIH (64% vs 27%, P = .043). A trend was observed for more cases of DNAIH showing severe inflammation (36% vs 9%, P = .09) and submassive necrosis compared with RAIH (23% vs 0%, P = .086). A trend for more advanced fibrosis was also noted in the RAIH group (27% vs 5%, P = .059). Three patients with RAIH lost their grafts because of RAIH. Five-year disease-specific graft survival (GS) (P = .012) and overall GS (P = .015) were worse in patients with RAIH. Complement component 4d immunohistochemistry was positive in 2 patients with RAIH and 3 with DNAIH but showed no correlation with GS or other parameters. CONCLUSIONS RAIH seems to have a more aggressive clinical course than DNAIH and warrants closer clinical follow-up and aggressive treatment.
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Affiliation(s)
- Iván A González
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
- Department of Pathology, Yale School of Medicine, New Haven, CT
| | - Christopher P Hartley
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - ILKe Nalbantoglu
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
- Department of Pathology, Yale School of Medicine, New Haven, CT
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28
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Cruz AJSD, Castilho LSD, Contarini LCS, Silva MEDSE, Abreu MHNG. Dental Findings of Kidney and Liver Transplantation Patients from a Brazilian Oral Health Care Service. PESQUISA BRASILEIRA EM ODONTOPEDIATRIA E CLÍNICA INTEGRADA 2021. [DOI: 10.1590/pboci.2021.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
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29
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Jogi S, Varanai R, Bantu SS, Manne A. Selecting the first line treatment in non-metastatic hepatocellular carcinoma - comparing clinical practice guidelines. Oncol Rev 2020; 14:515. [PMID: 33425223 PMCID: PMC7771021 DOI: 10.4081/oncol.2020.515] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Accepted: 11/18/2020] [Indexed: 02/08/2023] Open
Abstract
Primary malignancy of the liver or hepatocellular carcinoma (HCC) is unique in its presentation, disease process, and management. Unlike breast or colon cancer, the staging of HCC depends on performance status and baseline liver function along with pathological characteristics. Apart from traditional options like surgery and systemic therapy, effective management can be achieved in selected cases with liver transplant and locoregional therapy (LRT) like transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and ablation. Liver study societies and cancer groups across the globe proposed guidelines to aid the treating physicians in choosing first-line treatment for liver cancer. It is tough to compare these guidelines as they differ not only in treatment recommendations but also in risk assessment (and staging). The approach to the same patient may be different in the country he or she is managed. In clinical practice, decisions are usually taken on the consensus of multidisciplinary tumor boards and do not necessarily adhere to any guidelines. In the early (and very early) stage HCC, curative options like surgery, transplant, and ablation are recommended. In intermediate stage HCC, LRT (TACE and TARE) is preferred in the first line and systemic therapy for treatment failure or residual disease. Systemic therapy, including the atezolizumab/bevacizumab combination and tyrosine kinase inhibitors (TKI) like sorafenib and lenvatinib, is used for advanced stages. Supportive care is advised for terminal stage HCC.
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Affiliation(s)
- Soumya Jogi
- Alluri Sitarama Raju Academy of Medical Sciences, Eluru, Andhra Pradesh, India
| | | | | | - Ashish Manne
- The James Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA
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30
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Olimpiadi YB, Brownson KE, Kahn JA, Kim B, Han H, Khemichian S, Fong TL, Kang I, Terando A, Lang JE. Treatment and Outcomes of Early Stage Breast Cancer in Patients with Hepatic Dysfunction. J Surg Res 2020; 256:212-219. [PMID: 32711178 PMCID: PMC7854813 DOI: 10.1016/j.jss.2020.06.022] [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: 03/02/2020] [Revised: 06/08/2020] [Accepted: 06/16/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND There exists a dogma of surgical nihilism for patients with cirrhosis and breast cancer causing de-escalation of surgery and impacting survival. We hypothesized that breast cancer surgery would not result in a significant change in the Model for End-Stage Liver Disease-Sodium (MELD-Na) scores before and after surgery. METHODS We performed a single institutional retrospective review of medical records between January 2013 and July 2019 of patients with concurrent cirrhosis and breast cancer. We used the nonparametric Friedman test to compare differences in MELD-Na scores. RESULTS Eight patients with both cirrhosis and breast cancer were identified. Median follow-up was 30.5 mo. Half of the patients had Child-Pugh class A cirrhosis and half had Child-Pugh class B cirrhosis. Six (75%) patients underwent lumpectomy and two (25%) underwent mastectomy. There was no statistically significant difference (P = 0.66) in median MELD-Na score before surgery (16) and after surgery (18). Two (25%) patients experienced postoperative complications. Three patients were listed for liver transplantation. Of three listed patients, two (25%) patients underwent successful liver transplantation after breast surgery. One (12.5%) patient died without transplant. Three (37.5%) patients were alive for more than 5 y after breast cancer diagnosis without evidence of cancer recurrence. The eighth patient has remained breast cancer free for more than 6 mo since her surgery. CONCLUSIONS Surgery for patients with Child-Pugh class A and B cirrhosis and early stage breast cancer did not result in a significant change in MELD-Na score before and after surgery, suggesting that selected patients may benefit from breast cancer surgery with curative intent.
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Affiliation(s)
- Yuliya B Olimpiadi
- Division of Breast, Endocrine and Soft Tissue Surgery, Department of Surgery, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
| | - Kirstyn E Brownson
- Division of Breast, Endocrine and Soft Tissue Surgery, Department of Surgery, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
| | - Jeffrey A Kahn
- Liver Transplant Program, Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California
| | - Brian Kim
- Liver Transplant Program, Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California
| | - Hyosun Han
- Liver Transplant Program, Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California
| | - Saro Khemichian
- Liver Transplant Program, Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California
| | - Tse-Ling Fong
- Liver Transplant Program, Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California
| | - Irene Kang
- Division of Medical Oncology, Department of Medicine, University of Southern California, Los Angeles, California
| | - Alicia Terando
- Division of Breast, Endocrine and Soft Tissue Surgery, Department of Surgery, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
| | - Julie E Lang
- Division of Breast, Endocrine and Soft Tissue Surgery, Department of Surgery, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
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Pu S, Jin S, Xiang B, Yang J, Li K, Xie X, Huang B, Lai W, Yan L, Zhang M, Dong C. The current status and outcomes of pediatric liver transplantation in western China: A multi-center retrospective study. Pediatr Transplant 2020; 24:e13810. [PMID: 32845541 DOI: 10.1111/petr.13810] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Revised: 07/02/2020] [Accepted: 07/06/2020] [Indexed: 02/05/2023]
Abstract
This retrospective study was conducted to examine the development and current status of pediatric liver transplantation (LT) in western China. Clinical, demographic, morbidity, and mortality data were collected to analyze. It included 260 consecutive pediatric LTs performed at three centers in western China between January 2000 and May 2019. Kaplan-Meier graft survival rates at 1, 3, 5, and 10 years were 82.1%, 77.2%, 76.6%, and 76.6%, respectively; corresponding patient survival rates were 84.7%, 80.7%, 80.0%, and 80.0%, respectively. More patients underwent living donor liver transplantation (LDLT; n = 188 (73.4%)) than deceased-donor liver transplantation (DDLT; n = 68 (26.6%)). Survival was better after LDLT (91.5%, 86.6%, and 80.6% at 1, 3, and 5 years, respectively) than after DDLT (80.9%, 72.4%, and 63.9%, respectively; P < .05). Biliary atresia was the leading LT indication (n = 141 (55.1%)), followed by metabolic disease (n = 36 (14.1%)), which was associated with the best recipient survival (88.5% at 5 years). The transplant era and graft-to-recipient body weight ratio (GRWR) also significantly predicted overall survival. Survival rates at 5 years were worst in 2000-2005 (54.5%) and best for GRWRs of 0.8%-4% (80.4%). The development of pediatric LT in western China began slowly, but the quantity and quality of pediatric LT has progressed in recent years. This procedure is now a promising and reliable treatment for children with end-stage liver disease in western China.
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Affiliation(s)
- Siyu Pu
- Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Shuguang Jin
- Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Bo Xiang
- Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Jiayin Yang
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Kewei Li
- Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Xiaolong Xie
- Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Bin Huang
- Department of Vascular Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Wei Lai
- Pediatric Intensive Care Unit, Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Lunan Yan
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Mingman Zhang
- Laboratory of Surgery, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Chunqiang Dong
- Division of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, China
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Xu K, Meng Z, Mu X, Sun B, Chai Y. One Single Site Clinical Study: To Evaluate the Safety and Efficacy of Immunotherapy With Autologous Dendritic Cells, Cytokine-Induced Killer Cells in Primary Hepatocellular Carcinoma Patients. Front Oncol 2020; 10:581270. [PMID: 33324558 PMCID: PMC7724106 DOI: 10.3389/fonc.2020.581270] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 10/21/2020] [Indexed: 12/24/2022] Open
Abstract
Dendritic cells (DCs) and cytokine-induced killer (CIK) cells play an important role in the anti-tumor immune response. In this study, we evaluated the clinical effectiveness of DC/CIK-CD24 immunotherapies to primary hepatocellular carcinoma patients who received radical resection. 36 resected primary hepatocellular carcinoma (HCC) patients were enrolled from August 2014 to December 2015. All patients received two or four times of DC/CIK immunotherapy after radical resection. 1-4 years patients' survival rates were evaluated during the follow-up. The 4-year survival rate of patients who received two times of immunotherapy was 47.1%, and the rate of those who received four times of immunotherapies was 52.6%. Compared to baseline, after receiving the DC/CIK-CD24 autotransfusion, the serum Treg concentration of the patients decreased, while CD3+, CD4+, CD56+ increased slightly. The adverse effect of immunotherapy was I-II° transient fever and could be tolerable. DC/CIK-CD24 immunotherapy can delay the relapse time.
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Affiliation(s)
- Kaiyue Xu
- Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zhengjie Meng
- College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, China
| | - Xiaoxin Mu
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China
| | - Beicheng Sun
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Yi Chai
- Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Nishi M, Matsumoto T, Fujisawa K, Suehiro Y, Takami T, Yamamoto N, Yamasaki T, Sakaida I. Mesenchymal Stem Cells Induce a Fibrolytic Phenotype By Regulating mmu-miR-6769b-5p Expression in Macrophages. Stem Cells Dev 2020; 29:1457-1466. [PMID: 32962510 DOI: 10.1089/scd.2020.0123] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Liver transplantation is the only radical treatment for decompensated cirrhosis, but its use is limited owing to a shortage of donors; hence, there is an urgent need for new treatments. Previously, we developed a liver-regeneration therapy using autologous bone marrow-derived mesenchymal stem cells (BMSCs), which is under clinical investigation. Cell-cell interactions between BMSCs and macrophages (Mφs) participate in the improvement of liver function and alleviation of liver fibrosis, although the associated mechanisms have not been elucidated. Therefore, in this study, we investigated phenotypic changes in Mφs caused by interactions with BMSCs, as well as the underlying mechanisms. Co-culturing lipopolysaccharide (LPS)-stimulated murine bone marrow-derived Mφs (BMDMs) with BMSCs substantially upregulated matrix metalloproteinase 9 (Mmp9), Mmp12, and Mmp13 expression, and downregulated tumor necrosis factor alpha (Tnfα) expression. To identify humoral factors involved in phenotypic changes occurring in Mφs, microarray analysis was performed with microRNAs (miRNAs) derived from extracellular vesicles in the supernatant of co-cultured BMSCs and LPS-stimulated BMDMs. We found that miR-6769b-5p was highly expressed and that transfecting miR-6769b-5p mimic upregulated MMP9 in LPS-stimulated BMDMs and downregulated Tnfα and interleukin-1 beta (Il-1β). MiR-6769b-5p expression in BMDMs was decreased by LPS stimulation but was increased by co-culture with BMSCs. Microarray and pathway analyses of gene expression in LPS-stimulated, miR-6769b-5p-transfected BMDMs revealed changes in the eukaryotic initiation factor 2-signaling pathway and decreased the expression of activating transcription factor 4 (Atf4). LPS-stimulated BMDMs exhibited increased MMP9 expression and decreased the expression of Tnfα and Il-1β by ATF4 knockdown. These findings indicate that upregulating miR-6769b-5p in BMDMs induced a fibrolytic phenotype, where MMP9 was highly expressed and inflammatory cytokine expression was decreased by the suppression of ATF4 expression. These findings imply that regulating miR-6769b-5p or ATF4 expression in BMDMs may be helpful for treating chronic liver disease.
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Affiliation(s)
- Maiko Nishi
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Toshihiko Matsumoto
- Department of Oncology and Laboratory Medicine, and Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Koichi Fujisawa
- Department of Liver Regenerative Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Yutaka Suehiro
- Department of Oncology and Laboratory Medicine, and Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Taro Takami
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Naoki Yamamoto
- Yamaguchi University Health Administration Center, Yamaguchi University, Yamaguchi, Japan
| | - Takahiro Yamasaki
- Department of Oncology and Laboratory Medicine, and Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Isao Sakaida
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan
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Tanaka S, Fujita K, Kanaoka M, Makimoto K, Yakushiji K, Tanaka R, Harada N, Ikegami T, Yoshizumi T. Prospective study of objective physical activity and quality of life in living donor liver transplant recipients. Jpn J Nurs Sci 2020; 17:e12362. [PMID: 33470540 DOI: 10.1111/jjns.12362] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 06/09/2020] [Accepted: 06/17/2020] [Indexed: 12/25/2022]
Abstract
AIM The aims of this study were to: (a) describe the physical activity (PA) and quality of life (QOL) in living donor liver transplant (LDLT) recipients pre-operatively and at 3 months and 6 months post-operatively; (b) compare PA and QOL at 6 months post-operatively with a healthy control group; and (c) explore pre-operative factors that predict PA changes. METHODS Patients over 20 years of age who were undergoing LDLT were recruited. PA was measured based on the number of steps/day and time spent performing moderate-to-vigorous PA (MVPA) during 1 week using an accelerometer. QOL was assessed based on a physical (PCS) and mental (MCS) component summary of the eight-item Short-Form Health Survey. The LDLT and healthy control groups were matched for age (±3 years) and gender. Pre-operative factors predicting a change in PA were calculated using a generalized linear mixed model. RESULTS Twenty-four patients completed the study. By 6 months post-LDLT, the MCS and PCS were comparable to those in the control group. The number of steps (3,887 steps/day) and MVPA (29.3 min/week) showed significant improvement by 6 months post-operatively, but remained much lower compared with those in the control group. The multivariate analysis showed that younger age (p < .01, p = .04) and higher skeletal muscle mass (SMM; p < .01, p = .03) were predictors of improvement in number of steps and MVPA. CONCLUSION This study suggests the need for pre-operative interventions by healthcare professionals that focus on outcomes such as improving low SMM to facilitate post-operative PA recovery.
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Affiliation(s)
- Satomi Tanaka
- Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kimie Fujita
- Division of Health Sciences, Graduate School of Medicine, Kyushu University, Fukuoka, Japan
| | - Maki Kanaoka
- School of Nursing, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Kiyoko Makimoto
- Department of Nursing, School of Nursing and Rehabilitation, Konan Women's University, Kobe, Japan
| | - Kanako Yakushiji
- Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Rumi Tanaka
- Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Noboru Harada
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Toru Ikegami
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Castillo-Ledesma N, Corriols-Noval P, López-Simón E, Viana-Cora A, Casafont-Morencos F, Ezcurra-Acedo I, Morales-Angulo C. Head and neck cancer screening in patients eligible for liver transplantation. ACTA OTORRINOLARINGOLOGICA ESPANOLA 2020. [DOI: 10.1016/j.otoeng.2020.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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36
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Castillo-Ledesma N, Corriols-Noval P, López-Simón E, Viana-Cora A, Casafont-Morencos F, Ezcurra-Acedo I, Morales-Angulo C. Cribado de cáncer de cabeza y cuello en pacientes candidatos a trasplante hepático. ACTA OTORRINOLARINGOLOGICA ESPANOLA 2020; 71:249-252. [DOI: 10.1016/j.otorri.2020.02.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2018] [Revised: 01/14/2020] [Accepted: 02/04/2020] [Indexed: 02/08/2023]
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Wiering L, Sponholz F, Brandl A, Dziodzio T, Jara M, Dargie R, Eurich D, Schmelzle M, Sauer IM, Aigner F, Kotsch K, Pratschke J, Öllinger R, Ritschl PV. Perioperative Pleural Drainage in Liver Transplantation: A Retrospective Analysis from a High-Volume Liver Transplant Center. Ann Transplant 2020; 25:e918456. [PMID: 31949125 PMCID: PMC6988474 DOI: 10.12659/aot.918456] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Pleural effusions represent a common complication after liver transplantation (LT) and chest drain (CD) placement is frequently necessary. MATERIAL AND METHODS In this retrospective cohort study, adult LT recipients between 2009 and 2016 were analyzed for pleural effusion formation and its treatment within the first 10 postoperative days. The aim of the study was to compare different settings of CD placement with regard to intervention-related complications. RESULTS Overall, 597 patients met the inclusion criteria, of which 361 patients (60.5%) received at least 1 CD within the study period. Patients with a MELD >25 were more frequently affected (75.7% versus 56.0%, P<0.001). Typically, CDs were placed in the intensive care unit (ICU) (66.8%) or in the operating room (14.1% during LT, 11.5% in the context of reoperations). In total, 97.0% of the patients received a right-sided CD, presumably caused by local irritations. Approximately one-third (35.4%) of ICU-patients required pre-interventional optimization of coagulation. Of the 361 patients receiving a CD, 15 patients (4.2%) suffered a post-interventional hemorrhage and 6 patients (1.4%) had a pneumothorax requiring further treatment. Less complications were observed when the CD was performed in the operating room compared to the ICU: 1 out 127 patients (0.8%) versus 20 out of 332 patients (6.0%); P=0.016. CONCLUSIONS CD placement occurring in the operating room was associated with fewer complications in contrast to placement occurring in the ICU. Planned CD placement in the course of surgery might be favorable in high-risk patients.
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Affiliation(s)
- Leke Wiering
- Department of Surgery, Campus Charité Mitte
- Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Felix Sponholz
- Department of Surgery, Campus Charité Mitte
- Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Andreas Brandl
- Department of Surgery, Campus Charité Mitte
- Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Tomasz Dziodzio
- Department of Surgery, Campus Charité Mitte
- Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Maximilian Jara
- Department of Surgery, Campus Charité Mitte
- Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Richard Dargie
- Division of Emergency and Acute Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Dennis Eurich
- Department of Surgery, Campus Charité Mitte
- Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Moritz Schmelzle
- Department of Surgery, Campus Charité Mitte
- Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Igor M Sauer
- Department of Surgery, Campus Charité Mitte
- Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Felix Aigner
- Department of Surgery, Campus Charité Mitte
- Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Katja Kotsch
- Department of Surgery, Campus Charité Mitte
- Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Johann Pratschke
- Department of Surgery, Campus Charité Mitte
- Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Robert Öllinger
- Department of Surgery, Campus Charité Mitte
- Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Paul Viktor Ritschl
- Department of Surgery, Campus Charité Mitte
- Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,BIH Charité Clinician Scientist Program, Berlin Institute of Health (BIH), Berlin, Germany
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Liver Transplantation. THE CRITICALLY ILL CIRRHOTIC PATIENT 2020. [PMCID: PMC7122092 DOI: 10.1007/978-3-030-24490-3_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The field of liver transplantation has changed since the MELD scoring system became the most widely used donor allocation tool. Due to the MELD-based allocation system, sicker patients with higher MELD scores are being transplanted. Persistent organ donor shortages remain a challenging issue, and as a result, the wait-list mortality is a persistent problem for most of the regions. This chapter focuses on deceased donor and live donor liver transplantation in patients with complications of portal hypertension. Special attention will also be placed on donor-recipient matching, perioperative management of transplant patients, and the impact of hepatic hemodynamics on transplantation.
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Furuya K, Zheng YW, Sako D, Iwasaki K, Zheng DX, Ge JY, Liu LP, Furuta T, Akimoto K, Yagi H, Hamada H, Isoda H, Oda T, Ohkohchi N. Enhanced hepatic differentiation in the subpopulation of human amniotic stem cells under 3D multicellular microenvironment. World J Stem Cells 2019; 11:705-721. [PMID: 31616545 PMCID: PMC6789189 DOI: 10.4252/wjsc.v11.i9.705] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 08/06/2019] [Accepted: 08/27/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND To solve the problem of liver transplantation donor insufficiency, an alternative cell transplantation therapy was investigated. We focused on amniotic epithelial cells (AECs) as a cell source because, unlike induced pluripotent stem cells, they are cost-effective and non-tumorigenic. The utilization of AECs in regenerative medicine, however, is in its infancy. A general profile for AECs has not been comprehensively analyzed. Moreover, no hepatic differentiation protocol for AECs has yet been established. To this end, we independently compiled human AEC libraries, purified amniotic stem cells (ASCs), and co-cultured them with mesenchymal stem cells (MSCs) and human umbilical vein endothelial cell (HUVECs) in a 3D system which induces functional hepatic organoids. AIM To characterize AECs and generate functional hepatic organoids from ASCs and other somatic stem cells. METHODS AECs, MSCs, and HUVECs were isolated from the placentae and umbilical cords of cesarean section patients. Amnion and primary AEC stemness characteristics and heterogeneity were analyzed by immunocytochemistry, Alkaline phosphatase (AP) staining, and flow cytometry. An adherent AEC subpopulation was selected and evaluated for ASC purification quality by a colony formation assay. AEC transcriptomes were compared with those for other hepatocytes cell sources by bioinformatics. The 2D and 3D culture were compared by relative gene expression using several differentiation protocols. ASCs, MSCs, and HUVECs were combined in a 3D co-culture system to generate hepatic organoids whose structure was compared with a 3D AEC sphere and whose function was elucidated by immunofluorescence imaging, periodic acid Schiff, and an indocyanine green (ICG) test. RESULTS AECs have certain stemness markers such as EPCAM, SSEA4, and E-cadherin. One AEC subpopulation was also either positive for AP staining or expressed the TRA-1-60 and TRA-1-81 stemness markers. Moreover, it could form colonies and its frequency was enhanced ten-fold in the adherent subpopulation after selective primary passage. Bioinformatics analysis of ribose nucleic acid sequencing revealed that the total AEC gene expression was distant from those of pluripotent stem cells and hepatocytes but some gene expression overlapped among these cells. TJP1, associated with epidermal growth factor receptor, and MET, associated with hepatocyte growth factor receptor, were upregulated and may be important for hepatic differentiation. In conventional flat culture, the cells turned unviable and did not readily differentiate into hepatocytes. In 3D culture, however, hepatic gene expression of the AEC sphere was elevated even under a two-step differentiation protocol. Furthermore, the organoids derived from the MSC and HUVEC co-culture showed 3D structure with polarity, hepatic-like glycogen storage, and ICG absorption/elimination. CONCLUSION Human amniotic epithelial cells are heterogeneous and certain subpopulations have high stemness. Under a 3D co-culture system, functional hepatic organoids were generated in a multicellular microenvironment.
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Affiliation(s)
- Kinji Furuya
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
| | - Yun-Wen Zheng
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
- Institute of Regenerative Medicine and Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
- Department of Regenerative Medicine, School of Medicine, Yokohama City University, Yokohama 236-0004, Japan.
| | - Daisuke Sako
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
- Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510, Japan
| | - Kenichi Iwasaki
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
| | - Dong-Xu Zheng
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
| | - Jian-Yun Ge
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
| | - Li-Ping Liu
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
- Institute of Regenerative Medicine and Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
| | - Tomoaki Furuta
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
| | - Kazunori Akimoto
- Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510, Japan
| | - Hiroya Yagi
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
| | - Hiromi Hamada
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
| | - Hiroko Isoda
- Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan
| | - Tatsuya Oda
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
| | - Nobuhiro Ohkohchi
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
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Zhang L, Zhou D, Li J, Yan X, Zhu J, Xiao P, Chen T, Xie X. Effects of Bone Marrow-Derived Mesenchymal Stem Cells on Hypoxia and the Transforming Growth Factor beta 1 (TGFβ-1) and SMADs Pathway in a Mouse Model of Cirrhosis. Med Sci Monit 2019; 25:7182-7190. [PMID: 31550244 PMCID: PMC6775794 DOI: 10.12659/msm.916428] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Accepted: 05/09/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The role of bone marrow-derived mesenchymal stem cells (BM-MSCs) in liver fibrosis remains poorly understood. This study aimed to use a mouse model of carbon tetrachloride (CCL₄)-induced liver fibrosis to investigate the effects of BM-MSCs during liver hypoxia and the involvement of the transforming growth factor beta 1 (TGF-ß1) and SMADs pathway. MATERIAL AND METHODS Thirty C57BL/6 mice were randomly divided into the control group (n=10), the model group (n=10), and the BM-MSC-treated model group (n=10). In the model group, liver fibrosis was induced by intraperitoneal injection of CCl₄. BM-MSCs were transplanted after 12 weeks of CCl₄ treatment. The serum biochemical parameters and histological changes in the liver, using histochemical stains, were investigated. The expression of collagen type I (collagen I), alpha-smooth muscle actin (alpha-SMA), TGF-ß1, SMAD3, SMAD7, hypoxia-inducible factor 1 alpha (HIF-1alpha), and vascular endothelial grow factor (VEGF) were assessed by immunohistochemistry and quantitative real-time polymerase chain (RT-qPCR) reaction. RESULTS Treatment with BM-MSCs reduced the expression of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared with the model group, and reduced liver fibrosis determined histologically using hematoxylin and eosin (H&E) and Masson's trichrome staining compared with the model group. The area of liver fibrosis decreased after BM-MSCs treatment (p<0.05). Protein expression of HIF-1alpha and VEGF were decreased after BM-MSCs treatment (p<0.05). Transplantation of BM-MSCs reduced the mRNA expression of TGF-ß1, collagen I, alpha-SMA, and SMAD3 (p<0.05). CONCLUSIONS BM-MSC transplantation reduced CCl₄-induced murine liver fibrosis, indicating that in a hypoxic microenvironment, BM-MSCs may inhibit the TGFß-1/SMADs pathway.
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Affiliation(s)
- Liting Zhang
- State Key Laboratory of Cryospheric Science, Northwest Institute of Eco-Environmental and Resources, Chinese Academy of Sciences, Lanzhou, Gansu, P.R. China
- Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, Gansu, P.R. China
| | - Dan Zhou
- The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, P.R. China
| | - Junfeng Li
- Institute of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, Gansu, P.R. China
| | - Xiaoming Yan
- The 4 People’s Hospital of Qinghai Province, Xining, Qinghai, P.R. China
| | - Jun Zhu
- Department of Pathology of Donggang Branch, The First Hospital of Lanzhou University, Lanzhou, Gansu, P.R. China
| | - Ping Xiao
- Institute of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, Gansu, P.R. China
| | - Tuo Chen
- State Key Laboratory of Cryospheric Science, Northwest Institute of Eco-Environmental and Resources, Chinese Academy of Sciences, Lanzhou, Gansu, P.R. China
| | - Xiaodong Xie
- Institute of Medical Genetics, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, P.R. China
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Plotogea O, Ilie M, Sandru V, Chiotoroiu A, Bratu O, Diaconu C. Cardiovascular and Metabolic Consequences of Liver Transplantation: A Review. MEDICINA (KAUNAS, LITHUANIA) 2019; 55:489. [PMID: 31443295 PMCID: PMC6722584 DOI: 10.3390/medicina55080489] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/19/2019] [Revised: 08/03/2019] [Accepted: 08/09/2019] [Indexed: 12/14/2022]
Abstract
Liver transplantation (LT) is considered the curative treatment option for selected patients who suffer from end-stage or acute liver disease or hepatic malignancy (primary). After LT, patients should be carefully monitored for complications that may appear, partially due to immunosuppressive therapy, but not entirely. Cardiovascular diseases are frequently encountered in patients with LT, being responsible for high morbidity and mortality. Patients with underlying cardiovascular and metabolic pathologies are prone to complications after the transplant, but these complications can also appear de novo, mostly associated with immunosuppressants. Metabolic syndrome, defined by obesity, hypertension, dyslipidemia, and hyperglycemia, is diagnosed among LT recipients and is aggravated after LT, influencing the long-term survival. In this review, our purpose was to summarize the current knowledge regarding cardiovascular (CV) diseases and the metabolic syndrome associated with LT and to assess their impact on short and long-term morbidity and mortality.
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Affiliation(s)
- Oana Plotogea
- Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", 050474 Bucharest, Romania
- Gastroenterology Clinic, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Madalina Ilie
- Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", 050474 Bucharest, Romania
- Gastroenterology Clinic, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Vasile Sandru
- Gastroenterology Clinic, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Alexandru Chiotoroiu
- Surgery Clinic, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Ovidiu Bratu
- Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", 050474 Bucharest, Romania
- Urology Clinic, Emergency University Central Military Hospital, 010242 Bucharest, Romania
| | - Camelia Diaconu
- Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", 050474 Bucharest, Romania.
- Internal Medicine Clinic, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania.
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Liver transplantation for unresectable malignancies: Beyond hepatocellular carcinoma. Eur J Surg Oncol 2019; 45:2268-2278. [PMID: 31387755 DOI: 10.1016/j.ejso.2019.07.024] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Revised: 07/02/2019] [Accepted: 07/18/2019] [Indexed: 12/12/2022] Open
Abstract
Indications for liver transplantation have expanded over the past few decades owing to improved outcomes and better understanding of underlying pathologies. In particular, there has been a growing interest in the field of transplant oncology in recent years that has led to considerable developments which have pushed the boundaries of malignant indications for liver transplantation beyond hepatocellular carcinoma (HCC). In this article, we review and summarise the published evidence for liver transplantation in non-HCC primary and metastatic liver malignancies and highlight ongoing clinical trials that address unresolved questions therein. We also examine the current technical, immunological and oncological challenges that face liver transplantation in this growing field and explore potential approaches to overcome these barriers.
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Shin J, Yu JH, Jin YJ, Suh YJ, Kim DH, Byun S, Lee JW. Effective therapeutic options for elderly patients with hepatocellular carcinoma: A nationwide cohort study. Medicine (Baltimore) 2019; 98:e16150. [PMID: 31348228 PMCID: PMC6708965 DOI: 10.1097/md.0000000000016150] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
We evaluated the post-treatment overall survival (OS) of elderly hepatocellular carcinoma (HCC) patients.The archived records of 10,578 HCC patients registered at the Korean Central Cancer Registry from 2008 through 2014 were retrospectively analyzed. In this registry, we selected Barcelona Clinic Liver Cancer (BCLC) 0, A, or B staged HCC patients (n = 4744) treated by surgical resection (SR), local ablation therapy (LAT), or locoregional therapy (LRT). OSs in nonelderly (<70 years) and elderly (≥70 years) patients were compared after propensity score matching (PSM).In BCLC 0-A staged HCC, the cumulative OS rates of elderly patients were poorer than those of nonelderly patients after PSM (P < .001), but not in those with BCLC stage B (P > .05). In BCLC 0-A staged elderly patients, OS after SR was significantly better than after LAT (P = .005) or LRT (P < .001). In BCLC B staged elderly patients, SR achieved better OS than LRT (P = .006). Multivariable analysis showed that LAT (hazard ratio [HR] 1.52, P = .048) or LRT (HR, 2.01, P < .001) as compared with SR, and large (>3 cm) tumor size (HR1.49, P = .018) were poor predictors of OS for elderly patients with BCLC stage 0-A, and that LRT (HR, 2.64, P = .042) was a poor predictor for those with BCLC stage B.SR provided a better OS rate than LAT or LRT in elderly HCC patients with BCLC stage 0-A, than LRT in those with BCLC stage B. SR should be considered the first therapeutic option even in elderly HCC patients with these stages.
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Affiliation(s)
- Jongbeom Shin
- Department of Internal Medicine, Inha University Hospital
| | - Jung Hwan Yu
- Department of Internal Medicine, Inha University Hospital
- The Korean Liver Cancer Study Group, South Korea
| | - Young-Joo Jin
- Department of Internal Medicine, Inha University Hospital
- The Korean Liver Cancer Study Group, South Korea
| | - Young Ju Suh
- Department of Biomedical Sciences, College of Medicine
| | - Deuck Hwa Kim
- Department of Statistics, Inha University, Incheon, South Korea
| | - Seyoun Byun
- Department of Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, UT
| | - Jin-Woo Lee
- Department of Internal Medicine, Inha University Hospital
- The Korean Liver Cancer Study Group, South Korea
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Koczkodaj P, Straś W, Czerwiński J, Małkowski P, Panczyk M, Gotlib J. Evolution of Indications for Liver Transplantation (LTx) in the Years 2001-2017 in Poland. Ann Transplant 2019; 24:312-318. [PMID: 31147531 PMCID: PMC6561144 DOI: 10.12659/aot.915958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Hepatitis B and C viruses have been recognized as undoubtedly carcinogenic to humans. In the Polish population, where most people are protected by HBV vaccinations, hepatocellular carcinoma (HCC) and its main cause, persistent HCV infection, significantly affect the demand for liver transplantations. MATERIAL AND METHODS The purpose of this study was to categorize the number of primary liver transplantations in Poland in the years 2001-2017 by cause and to analyze changes in LTx indications during this period. Data were sourced from POLTRANSPLANT, the Organization and Coordination Center for Transplantation in Poland. Additionally, we compared the numbers of HCC cases and hepatitis B and C cases during this period. RESULTS In the analyzed period, in Poland, 3332 primary liver transplantations were performed. Overall, 44% (1456) of LTx cases were combined with HBV and/or HCV and/or HCC. In this group, transplants in patients with only 1 specific factor - HCV - formed the largest cohort, accounting for about 40% (581) of cases. Transplants in patients who only had HBV and in those who only had HCC accounted for 12% (185) and 5% (69), respectively. CONCLUSIONS The analyzed data suggest that HCV infections are a significant public health problem in Poland, as is also reflected by the growing number of LTx performed due to HCC. To limit the numbers of HCV and HCC cases, immediate implementation of a Polish National Program against HCV should be considered.
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Affiliation(s)
- Paweł Koczkodaj
- Division of Teaching and Outcomes of Education, Medical University of Warsaw, Warsaw, Poland.,Department of Epidemiology and Cancer Prevention, Maria Skłodowska-Curie Institute Oncology Center, Warsaw, Poland
| | - Wojciech Straś
- Adamed Pharma, Commercial Operations Area, Warsaw, Poland
| | - Jarosław Czerwiński
- Departament of Emergency Medicine, First Faculty of Medicine, Medical University of Warsaw, Warsaw, Poland.,Polish Transplant Coordinating Center POLTRANSPLANT, Warsaw, Poland
| | - Piotr Małkowski
- Department of Surgical and Transplantation Nursing and Extracorporeal Therapies, Medical University of Warsaw, Warsaw, Poland
| | - Mariusz Panczyk
- Division of Teaching and Outcomes of Education, Medical University of Warsaw, Warsaw, Poland
| | - Joanna Gotlib
- Division of Teaching and Outcomes of Education, Medical University of Warsaw, Warsaw, Poland
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Kornerup LS, Pflugrad H, Weissenborn K, Vilstrup H, Dam G. Cognitive impairment after liver transplantation: residual hepatic encephalopathy or posttransplant encephalopathy? Hepat Med 2019; 11:41-46. [PMID: 31040728 PMCID: PMC6456244 DOI: 10.2147/hmer.s144667] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Accepted: 02/25/2019] [Indexed: 12/22/2022] Open
Abstract
Liver transplantation (LT) represents the definitive treatment for end-stage liver disease. Cognitive impairment following LT is frequent, referred to as postliver transplant encephalopathy (PLTE). LT removes the underlying chronic liver disease, and until recently hepatic encephalopathy (HE) was assumed to be fully reversible after LT. However, increasing evidence indicates that some degree of cognitive impairment may be present after LT. To which extent PLTE reflects cognitive impairment caused by residual HE (RHE) or the combined effect of other factors affecting brain function before, during, and after LT is not clarified. None of the available psychometric and neurophysiological tests used for detecting HE is shown to be able to distinguish between etiologies. The available, mostly retrospective, clinical studies indicate a high prevalence of abnormal psychometric tests after LT, and not all seem to recover completely. The patients with earlier HE show the most marked improvements, suggesting that the clinical picture of the early PLTE, in fact, represents RHE. Other early post-LT etiologies for PLTE comprise cerebral ischemia, critical illness encephalopathy, and immunosuppressive therapy. Late-onset etiologies comprise diabetes and hypertension, among others. PLTE regardless of etiology is a worrying issue and needs more attention in the form of mechanistic research, development of diagnostic/discriminative tools, and standardized prospective clinical studies.
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Affiliation(s)
- Linda Skibsted Kornerup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N, Denmark
| | - Henning Pflugrad
- Department of Neurology, Hannover Medical School, Hannover, Germany
| | | | - Hendrik Vilstrup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N, Denmark
| | - Gitte Dam
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N, Denmark
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Chang KV, Chen JD, Wu WT, Huang KC, Han DS. Association of loss of muscle mass with mortality in liver cirrhosis without or before liver transplantation: A systematic review and meta-analysis. Medicine (Baltimore) 2019; 98:e14373. [PMID: 30817561 PMCID: PMC6831322 DOI: 10.1097/md.0000000000014373] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Liver cirrhosis is a risk factor for the loss of muscle mass, which is associated with numerous adverse health outcomes. This meta-analysis aimed to examine whether loss of muscle mass was a predictor of increased mortality in cirrhotic patients without or before liver transplantation. METHODS Without language restriction, PubMed and Embase were searched for articles published from the earliest records to December 2018 investigating the influence of loss of muscle mass on survival of cirrhotic patients. Those who had undergone liver transplantation and had hepatocellular carcinoma were excluded. The main outcome was the hazard ratio (HR) for the association of mortality with loss of muscle mass, and the secondary outcome was the association of loss of muscle mass with Child-Pugh class and death caused by severe infection. RESULTS The meta-analysis included 16 observational studies, comprising 4070 participants. The pooled crude and adjusted HRs for the association of mortality with loss of muscle mass were 2.05 (95% confidence interval [CI], 1.51-2.78) and 2.36 (95% CI, 1.61-3.46). Using Child-Pugh Class A as reference, the odds ratios (ORs) for the association of loss of muscle mass with Child-Pugh Class B and Class C were 1.68 (95% CI, 0.96-2.92) and 1.94 (95% CI, 0.66-5.65). Patients with loss of muscle mass were likely to have infection-related mortality (OR = 3.38, 95% CI, 0.61-18.88) but the association did not reach statistical significance. CONCLUSIONS Loss of muscle mass is associated with mortality in cirrhotic patients without or before liver transplantation. Future studies should be conducted to explore whether exercise and nutritional supplementation can reverse muscle mass loss and improve long-term survival.
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Affiliation(s)
- Ke-Vin Chang
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Bei-Hu Branch
- Community and Geriatric Medicine Research Center, National Taiwan University Hospital, Bei-Hu Branch
- Department of Physical Medicine and Rehabilitation, National Taiwan University College of Medicine, Taipei
| | - Jin-De Chen
- Community and Geriatric Medicine Research Center, National Taiwan University Hospital, Bei-Hu Branch
- Department of Gastroenterology, National Taiwan University Hospital, Bei-Hu Branch
| | - Wei-Ting Wu
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Bei-Hu Branch
| | - Kuo-Chin Huang
- Community and Geriatric Medicine Research Center, National Taiwan University Hospital, Bei-Hu Branch
- Department of Family Medicine, National Taiwan University College of Medicine, Taipei
| | - Der-Sheng Han
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Bei-Hu Branch
- Community and Geriatric Medicine Research Center, National Taiwan University Hospital, Bei-Hu Branch
- Department of Physical Medicine and Rehabilitation, National Taiwan University College of Medicine, Taipei
- Health Science and Wellness Center, National Taiwan University, Taipei, Taiwan
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Byun J, Kim KW, Choi SH, Lee S, Lee J, Song GW, Lee SG. Indirect Doppler ultrasound abnormalities of significant portal vein stenosis after liver transplantation. J Med Ultrason (2001) 2018; 46:89-98. [PMID: 30094765 DOI: 10.1007/s10396-018-0894-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Accepted: 07/17/2018] [Indexed: 01/10/2023]
Abstract
PURPOSE To determine indirect Doppler ultrasound (DUS) abnormalities associated with significant portal vein (PV) stenosis (PVS) in recipients of liver transplantation (LT). METHODS This retrospective study was approved by our institutional review board. Between February 2006 and May 2017, 41 LT recipients were diagnosed with significant PVS, defined as having more than 50% narrowing of PV diameter for any reason, including thrombosis or flow disturbance associated with prominent collateral vessels on portal venography. We reviewed the DUS findings of hepatic arteries (HAs) as well as PVs of them, before and after treatment of PVS, and in comparison, with a one-to-one case-matched control. Inter-group comparison of frequency in DUS abnormalities was performed using Chi square (χ2) with Fisher's exact test and McNemar's test. Diagnostic values of each abnormal DUS finding and combinations were also evaluated. RESULTS DUS of significant PVS showed "no demonstrable color flow," either at recipient PVs or anastomoses (26.7%), and showed turbulence (66.7%) and hepatofugal portal flow (HFPF; 20.0%) at the graft PVs. HFPF was more frequently observed in those with "no demonstrable color flow" at recipient PVs or anastomoses (p = 0.006). DUS of graft HAs revealed tardus-parvus waveforms (20.9%) and prolonged systolic acceleration times (16.3%), more commonly in the "no demonstrable color flow" group (p = 0.012). These indirect DUS abnormalities disappeared and resolved on follow-up DUS after treatment. In the control group, such Doppler abnormalities were less frequently shown than in the PVS group (p ≤ 0.01, respectively). When one of the portal-blood flow velocity (PFV)-related index abnormalities (such as increased time average velocity [TAV] at anastomosis and TAV ratio between recipient PV and anastomosis) or "no demonstrable color flow" were shown in DUS as well as one of the indirect DUS abnormalities, sensitivity, and specificity was 71.11 and 97.78%, respectively. CONCLUSION In addition to PFV-related abnormalities, DUS occasionally shows "no demonstrable color flow" either at recipient PVs or anastomoses, and indirect Doppler abnormalities such as turbulence, HFPF at graft PVs, and abnormal waveforms at graft HAs in LT recipients with significant PVS. The combination of PFV-related abnormalities and indirect DUS abnormalities would be helpful for diagnosis of PVS.
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Affiliation(s)
- Jieun Byun
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, South Korea
| | - Kyoung Won Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, South Korea.
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, South Korea
| | - Sunyoung Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, South Korea
| | - Jeongjin Lee
- School of Computer Science and Engineering, Soongsil University, Seoul, South Korea
| | - Gi Won Song
- Division of Liver Transplantation and Hepatobiliary Surgery, Departments of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Sung Gyu Lee
- Division of Liver Transplantation and Hepatobiliary Surgery, Departments of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
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Jin Y, Wang J, Li H, Gao S, Shi R, Yang D, Wang X, Wang X, Zhu L, Wang X, Chen C, Ning K, Gao Z, Xu J, Fu Q. Extracellular Vesicles Secreted by Human Adipose-derived Stem Cells (hASCs) Improve Survival Rate of Rats with Acute Liver Failure by Releasing lncRNA H19. EBioMedicine 2018; 34:231-242. [PMID: 30077720 PMCID: PMC6116414 DOI: 10.1016/j.ebiom.2018.07.015] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Revised: 07/08/2018] [Accepted: 07/12/2018] [Indexed: 02/07/2023] Open
Abstract
It has previously been reported that human adipose-derived stem cells (hASCs) can promote the regeneration of damaged tissues in rats with liver failure through a ‘paracrine effect’. Here we demonstrate a therapeutic effect of hASCs derived Extracellular Vesicles (EVs) on rat models with acute liver failure, as shown by the improvement of the survival rate by >70% compared to controls. Gene sequencing of rat liver revealed an increase in human long-chain non-coding RNA (lncRNA) H19 after hASC-derived EVs transplantation. When the H19 coding sequence was silenced in hASCs and EVs were then collected for treatment of rats with liver failure, we saw a decrease in the survival rate to 40%, compared to treatment with EVs generated from non-silenced hASCs. These data indicate that lncRNA H19 may be a potential therapeutic target for the treatment of liver failure.
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Affiliation(s)
- Yinpeng Jin
- Shanghai Public Health Clinical Center, Fudan University, Jinshan, Shanghai 201508, PR China.
| | - Junyi Wang
- Shanghai Liver Diseases Research Center, The 85th Hospital of PLA, Shanghai 200235, PR China
| | - Hongchao Li
- Shanghai Liver Diseases Research Center, The 85th Hospital of PLA, Shanghai 200235, PR China
| | - Shane Gao
- East Hospital, Tongji University School of Medicine, Shanghai 200120, PR China
| | - Rongfeng Shi
- Department of Interventional & Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China
| | - Danjing Yang
- East Hospital, Tongji University School of Medicine, Shanghai 200120, PR China
| | - Xianli Wang
- Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, PR China
| | - Xi Wang
- Shanghai Public Health Clinical Center, Fudan University, Jinshan, Shanghai 201508, PR China
| | - Liang Zhu
- East Hospital, Tongji University School of Medicine, Shanghai 200120, PR China
| | - Xiaojin Wang
- Shanghai Liver Diseases Research Center, The 85th Hospital of PLA, Shanghai 200235, PR China
| | - Chengwei Chen
- Shanghai Liver Diseases Research Center, The 85th Hospital of PLA, Shanghai 200235, PR China
| | - Ke Ning
- Department of Neuroscience, Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK
| | - Zhengliang Gao
- East Hospital, Tongji University School of Medicine, Shanghai 200120, PR China.
| | - Jun Xu
- East Hospital, Tongji University School of Medicine, Shanghai 200120, PR China.
| | - Qingchun Fu
- Shanghai Public Health Clinical Center, Fudan University, Jinshan, Shanghai 201508, PR China.
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Prognostic factors and treatment effect of standard-volume plasma exchange for acute and acute-on-chronic liver failure: A single-center retrospective study. Transfus Apher Sci 2018; 57:537-543. [PMID: 29880246 DOI: 10.1016/j.transci.2018.05.030] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Revised: 05/29/2018] [Accepted: 05/31/2018] [Indexed: 12/15/2022]
Abstract
Patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) have a high risk of mortality. Few studies have reported prognostic factors for patients receiving plasma exchange (PE) for liver support. We conducted a retrospective analysis using data of 55 patients with severe ACLF (n = 45) and ALF (n = 10) who received standard-volume PE (1-1.5 plasma volume) in the ICU. Hepatitis B virus infection accounts for the majority of ACLF (87%) and ALF (50%) patients. PE significantly improved the levels of total bilirubin, prothrombin time and liver enzymes (P<0.05). Thirteen ACLF patients (29%) and one ALF patient (10%) underwent liver transplantation. Two ALF patients (20%) recovered spontaneously without transplantation. The overall in-hospital survival rates for ACLF and ALF patients were 24% and 30%, and the transplant-free survival rates were 0% and 20%, respectively. For the 14 transplanted patients, the one-year survival rate was 86%. Multivariate analysis showed that pre-PE hemoglobin (P = 0.008), post-PE hemoglobin (P = 0.039), and post-PE CLIF-C ACLF scores (P = 0.061) were independent predictors of survival in ACLF. The post-PE CLIF-C ACLF scores ≥59 were a discriminator predicting the in-hospital mortality (area under the curve = 0.719, P = 0.030). Cumulative survival rates differed significantly between patients with CLIF-C ACLF scores ≤ 58 and those with CLIF-C ACLF scores ≥ 59 after PE (P< 0.05). The findings suggest that PE is mainly a bridge for liver transplantation and spontaneous recovery is exceptional even in patients treated with PE. A higher improvement in the post-PE CLIF-C ACLF score is associated with a superior in-hospital survival rate.
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Prabhu KS, Achkar IW, Kuttikrishnan S, Akhtar S, Khan AQ, Siveen KS, Uddin S. Embelin: a benzoquinone possesses therapeutic potential for the treatment of human cancer. Future Med Chem 2018; 10:961-976. [PMID: 29620447 DOI: 10.4155/fmc-2017-0198] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Accepted: 01/18/2017] [Indexed: 08/28/2023] Open
Abstract
Natural products have been gaining recognition and are becoming a significant part of research in the area of drug development and discovery. Phytochemicals derived from these sources have been comprehensively studied and have displayed a wide range of activities against many fatal diseases including cancer. One such product that has gained recognition from its pharmacological properties and nontoxic nature is embelin, obtained from Embelia ribes. Amid all the vivid pharmacological activities, embelin has gained its prominence in the area of cancer research. Embelin binds to the BIR3 domain of XIAP, preventing the association of XIAP and caspase-9 resulting in the suppression of cell growth, proliferation and migration of various types of cancer cells. Furthermore, embelin modulates anti-apoptotic pathways by suppressing the activity of NF-κB, PI3-kinase/AKT, JAK/STAT pathway - among others. The present review summarizes the various reported effects of embelin on different types of cancer cells and highlights the cellular mechanisms of action.
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Affiliation(s)
- Kirti S Prabhu
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
| | - Iman W Achkar
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
| | - Shilpa Kuttikrishnan
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
| | - Sabah Akhtar
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
| | - Abdul Q Khan
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
| | - Kodapully S Siveen
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
| | - Shahab Uddin
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
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