|
1
|
Jiménez-Romero C, Marcacuzco A, Caso O, Manrique A, García-Sesma A, Calvo J, Nutu A, Moreno-González E, Bernaldo de Quirós M, Justo Alonso I. Long-Term Outcomes of Liver Transplant Recipients. What Do Patients Die From? World J Surg 2025. [PMID: 40344290 DOI: 10.1002/wjs.12614] [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: 01/28/2025] [Revised: 03/30/2025] [Accepted: 04/27/2025] [Indexed: 05/11/2025]
Abstract
BACKGROUND Several advances in liver transplantation (LT) have provided an increased rate in 1-year patient survival, currently reported between 84.5% and 91.4%. However, this significant improvement is not widely maintained after the 1-year of follow-up. In this study, we analyze short-term and long-term results in LT recipients. METHODS A retrospective observational cohort study, including patients who underwent LT between 1990 and 2009 and were followed for a minimum 15-year period, analyzing the causes and risk factors of mortality and patient and graft survival from LT up to the last outpatient visit. RESULTS A total of 594 patients with LT were included (median age, 53-year and 69.7% male). The most common indications for LT were HCV-cirrhosis (267 patients), alcoholic cirrhosis (250 patients), and hepatocellular carcinoma (HCC) (144 patients). Post-LT complications were acute rejection in 44.1%, cardiovascular in 40.6%, chronic kidney disease in 40.1%, hypertension in 22.6%, and de novo tumors in 25.6%. Retransplantation was performed in 40 (6.7%) patients. A total of 388 (65.3%) patients died during a follow-up over 20 years: 106 (17.8%) in the first year post-LT; 76 (12.8%) between 2 and 5 years; 75 (12.6%) between 6 and 10 years; 73 (812.3%) between 11 and 15 years; 30 (5%) between 16 and 20 years; and 28 (4.7%) after 20 years. The overall causes of death were infection in 69 (11.6%) patients, cardiovascular complications in 58 (9.8%) patients, pulmonary complications in 8 (1.3%) patients, liver graft failure in 126 (21.2%) patients, HCC recurrence in 15 (2.6%) patients, de novo tumors in 72 (12.1%) patients, and miscellaneous in 40 (6.7%) patients. Rates of actuarial patient survival at 1-, 3-, 5-, 10-, 15-, and 20-year after LT were 82.7%, 75.6%, 70%, 58.6%, 45.2%, and 37.6%, respectively, and actuarial graft survival were 80%, 72.5%, 67.1%, 54.8%, 42.6%, and 34.6%, respectively. Advanced recipient age, blood transfusion, and infection were the main risk factors for patient mortality. CONCLUSIONS The highest mortality rate was within the first year of LT, and the most common causes of death were hepatic failure, de novo tumors, infection, cardiovascular disease, and HCC recurrence.
Collapse
Affiliation(s)
- Carlos Jiménez-Romero
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation, Doce de Octubre University Hospital. Instituto de Investigación Sanitaria Hospital Doce de Octubre (imas12), Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| | - Alberto Marcacuzco
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation, Doce de Octubre University Hospital. Instituto de Investigación Sanitaria Hospital Doce de Octubre (imas12), Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| | - Oscar Caso
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation, Doce de Octubre University Hospital. Instituto de Investigación Sanitaria Hospital Doce de Octubre (imas12), Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| | - Alejandro Manrique
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation, Doce de Octubre University Hospital. Instituto de Investigación Sanitaria Hospital Doce de Octubre (imas12), Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| | - Alvaro García-Sesma
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation, Doce de Octubre University Hospital. Instituto de Investigación Sanitaria Hospital Doce de Octubre (imas12), Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| | - Jorge Calvo
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation, Doce de Octubre University Hospital. Instituto de Investigación Sanitaria Hospital Doce de Octubre (imas12), Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| | - Anisa Nutu
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation, Doce de Octubre University Hospital. Instituto de Investigación Sanitaria Hospital Doce de Octubre (imas12), Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| | - Enrique Moreno-González
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation, Doce de Octubre University Hospital. Instituto de Investigación Sanitaria Hospital Doce de Octubre (imas12), Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| | - Mercedes Bernaldo de Quirós
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation, Doce de Octubre University Hospital. Instituto de Investigación Sanitaria Hospital Doce de Octubre (imas12), Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| | - Iago Justo Alonso
- Unit of Hepato-Pancreato-Biliary Surgery and Abdominal Organ Transplantation, Doce de Octubre University Hospital. Instituto de Investigación Sanitaria Hospital Doce de Octubre (imas12), Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, Madrid, Spain
| |
Collapse
|
|
2
|
Gabrielli F, Golfieri L, Nascimbeni F, Andreone P, Gitto S. Metabolic Disorders in Liver Transplant Recipients: The State of the Art. J Clin Med 2024; 13:1014. [PMID: 38398327 PMCID: PMC10889804 DOI: 10.3390/jcm13041014] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 02/05/2024] [Accepted: 02/08/2024] [Indexed: 02/25/2024] Open
Abstract
Liver transplantation represents a chief therapeutic approach for acute liver failure, end-stage liver disease and hepatocellular carcinoma. Despite witnessing advancements in short- and medium-term survival over recent decades, attributed to refinements in surgical techniques and immunosuppressive protocols, long-term mortality remains impervious to modification. Notably, cardiovascular disease emerges as a predominant cause of mortality among liver transplant recipients. This trend is accentuated by the increasing prominence of non-alcoholic steatohepatitis-related cirrhosis as an indication for liver transplantation. Moreover, the administration of immunosuppressive agents is intricately linked to the degradation of the metabolic profile in liver transplant recipients, thereby contributing to the initiation or exacerbation of cardiovascular risk factors, such as hypertension, diabetes, and dyslipidaemia. In addition, the post-liver transplantation period is marked by a decline in lifestyle quality and a failure to acknowledge the psychological distress experienced by patients throughout the transplant process. These factors can precipitate a deterioration in the patient's metabolic profile, exacerbated by suboptimal therapeutic compliance. This narrative review aims to comprehensively address the principal metabolic disorders intricately associated with liver transplantation.
Collapse
Affiliation(s)
- Filippo Gabrielli
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU di Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
- Department of Surgical Sciences, University of Bologna, 40126 Bologna, Italy
| | - Lucia Golfieri
- Clinical Psychology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant’Orsola, 40138 Bologna, Italy
| | - Fabio Nascimbeni
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU di Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Pietro Andreone
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU di Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
- Postgraduate School of Allergology and Clinical Immunology, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Stefano Gitto
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
| |
Collapse
|
|
3
|
Palaniyappan N, Peach E, Pearce F, Dhaliwal A, Campos-Varela I, Cant MR, Dopazo C, Trotter J, Divani-Patel S, Hatta AAZ, Hopkins L, Testa G, Bilbao A, Kasmani Z, Faloon S, Mirza DF, Klintmalm GB, Bilbao I, Asrani SK, Rajoriya N, Aravinthan AD. Long-term outcomes (beyond 5 years) of liver transplant recipients-A transatlantic multicenter study. Liver Transpl 2024; 30:170-181. [PMID: 37589505 DOI: 10.1097/lvt.0000000000000244] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 07/06/2023] [Indexed: 08/18/2023]
Abstract
The long-term (>5 y) outcomes following liver transplantation (LT) have not been extensively reported. The aim was to evaluate outcomes of LT recipients who have survived the first 5 years. A multicenter retrospective analysis of prospectively collected data from 3 high volume LT centers (Dallas-USA, Birmingham-UK, and Barcelona-Spain) was undertaken. All adult patients, who underwent LT since the inception of the program to December 31, 2010, and survived at least 5 years since their LT were included. Patient survival was the primary outcome. A total of 3682 patients who survived at least 5 years following LT (long-term survivors) were included. Overall, median age at LT was 52 years (IQR 44-58); 53.1% were males; and 84.6% were Caucasians. A total of 49.4% (n=1820) died during a follow-up period of 36,828 person-years (mean follow-up 10 y). A total of 80.2% (n=1460) of all deaths were premature deaths. Age-standardized all-cause mortality as compared to general population was 3 times higher for males and 5 times higher for females. On adjusted analysis, besides older recipients and older donors, predictors of long-term mortality were malignancy, cardiovascular disease, and dialysis. Implementation of strategies such as noninvasive cancer screening, minimizing immunosuppression, and intensive primary/secondary cardiovascular prevention could further improve survival.
Collapse
Affiliation(s)
- Naaventhan Palaniyappan
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, UK
- Nottingham Digestive Diseases Centre, Translational Medical Sciences, School of Medicine, University of Nottingham, UK
| | - Emily Peach
- Lifespan and Population Health, School of Medicine, University of Nottingham, UK
| | - Fiona Pearce
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, UK
- Lifespan and Population Health, School of Medicine, University of Nottingham, UK
| | | | - Isabel Campos-Varela
- Liver Unit, Department of Medicine, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Matthew R Cant
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Cristina Dopazo
- Department of Hepatobiliopancreatic Surgery and Transplants, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - James Trotter
- Baylor University Medical Center, Dallas, Texas, USA
| | | | | | - Laurence Hopkins
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | | | - Angela Bilbao
- Department of Hepatobiliopancreatic Surgery and Transplants, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Zain Kasmani
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Sarah Faloon
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Darius F Mirza
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham, UK
- Centre for Liver and Gastrointestinal Research, NIHR Birmingham Biomedical Research, University of Birmingham, Birmingham, UK
| | | | - Itxarone Bilbao
- Department of Hepatobiliopancreatic Surgery and Transplants, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | | | - Neil Rajoriya
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham, UK
- Institute of Immunology & Immunotherapy, University of Birmingham, UK
| | - Aloysious D Aravinthan
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, UK
- Nottingham Digestive Diseases Centre, Translational Medical Sciences, School of Medicine, University of Nottingham, UK
| |
Collapse
|
|
4
|
Fukumitsu K, Kaido T, Matsumura Y, Ito T, Ogiso S, Ishii T, Seo S, Hata K, Masui T, Taura K, Nagao M, Okajima H, Uemoto S, Hatano E. Pretransplant Renal Dysfunction Negatively Affects Prognosis After Living Donor Liver Transplantation: A Single-Center Retrospective Study. Transplant Proc 2023; 55:1623-1630. [PMID: 37414696 DOI: 10.1016/j.transproceed.2023.05.018] [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: 04/01/2023] [Accepted: 05/16/2023] [Indexed: 07/08/2023]
Abstract
BACKGROUND To evaluate the influence of preoperative renal function on prognosis after living donor liver transplantation (LDLT). METHODS Living donor liver transplantation cases were categorized into 3 groups as follows: renal failure with hemodialysis (HD; n = 42), renal dysfunction (RD; n = 94) (glomerular filtration rate <60 mL/min/1.73 m2), and normal renal function (NF; n = 421). The study used no prisoners, and participants were neither coerced nor paid. The manuscript complies with the Helsinki Congress and the Declaration of Istanbul. RESULTS Five-year overall survival (OS) rates were 59.0%, 69.3%, and 80.0% in the HD, RD, and NF groups, respectively (P < .01). The frequency of bacteremia within 90 days after LDLT was 76.2%, 37.2%, and 34.7%, respectively (P < .01 in HD vs RD and HD vs NF). Patients with bacteremia showed a worse outcome than those without (1-year OS, 65.6% vs 93.3%), thus corroborating the poor prognosis in the HD group. The high frequency of bacteremia in the HD group was mainly attributable to health care-associated bacterium, such as coagulase-negative Staphylococci, Enterococcus spp., and Pseudomonas aeruginosa. In the HD group, HD was started within 50 days before LDLT for acute renal failure in 35 patients, of which 29 (82.9%) successfully withdrew from HD after LDLT and demonstrated better prognosis (1-year OS, 69.0% vs 16.7%) than those who continued HD. CONCLUSIONS Preoperative renal dysfunction is associated with poor prognosis after LDLT, possibly due to a high incidence of health care-associated bacteremia.
Collapse
Affiliation(s)
- Ken Fukumitsu
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
| | - Toshimi Kaido
- Department of Gastroenterological and General Surgery, St. Luke's International Hospital, Tokyo, Japan
| | - Yasufumi Matsumura
- Department of Clinical Laboratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Takashi Ito
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Satoshi Ogiso
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takamichi Ishii
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Satoru Seo
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Koichiro Hata
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Toshihiko Masui
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kojiro Taura
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Miki Nagao
- Department of Clinical Laboratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Hideaki Okajima
- Department of Pediatric Surgery, Kanazawa Medical University, Ishikawa, Japan
| | | | - Etsuro Hatano
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| |
Collapse
|
|
5
|
Shimura Y, Kuramitsu K, Kido M, Komatsu S, Gon H, Fukushima K, Urade T, So S, Yoshida T, Arai K, Tsugawa D, Goto T, Asari S, Yanagimoto H, Toyama H, Ajiki T, Fukumoto T. Factors Predicting Over-Time Weight Increase After Liver Transplantation: A Retrospective Study. Transplant Proc 2023:S0041-1345(23)00218-X. [PMID: 37095008 DOI: 10.1016/j.transproceed.2023.03.045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 03/27/2023] [Indexed: 04/26/2023]
Abstract
BACKGROUND Post-transplantation weight control is important for long-term outcomes; however, few reports have examined postoperative weight change. This study aimed to identify perioperative factors contributing to post-transplantation weight change. METHODS Twenty-nine patients who underwent liver transplantation between 2015 and 2019 with an overall survival of >3 years were analyzed. RESULTS The median age, model for end-stage liver disease score, and preoperative body mass index (BMI) of the recipients were 57, 25, and 23.7, respectively. Although all but one recipient lost weight, the percentage of recipients who gained weight increased to 55% (1 month), 72% (6 months), and 83% (12 months). Among perioperative factors, recipient age ≤50 years and BMI ≤25 were identified as risk factors for weight gain within 12 months (P < .05), and patients with age ≤50 years or BMI ≤25 recipients gained weight more rapidly (P < .05). The recovery time of serum albumin level ≥4.0 mg/dL was not statistically different between the 2 groups. The weight change during the first 3 years after discharge was represented by an approximately straight line, with 18 and 11 recipients showing a positive and negative slope, respectively. Body mass index ≤23 was identified as a risk factor for a positive slope of weight gain (P <.05). CONCLUSIONS Although postoperative weight gain implies recovery after transplantation, recipients with a lower preoperative BMI should strictly manage body weight as they may be at higher risk of rapid weight increase.
Collapse
Affiliation(s)
- Yuhi Shimura
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
| | - Kaori Kuramitsu
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Masahiro Kido
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Shohei Komatsu
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Hidetoshi Gon
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Kenji Fukushima
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Takeshi Urade
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Shinichi So
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Toshihiko Yoshida
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Keisuke Arai
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Daisuke Tsugawa
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Tadahiro Goto
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Sadaki Asari
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Hiroaki Yanagimoto
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Hirochika Toyama
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Tetsuo Ajiki
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Takumi Fukumoto
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| |
Collapse
|
|
6
|
A Comprehensive Review on the Risk of Metabolic Syndrome and Cardiovascular Disease after Liver Transplantation. LIVERS 2022. [DOI: 10.3390/livers2020006] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Survival rates after liver transplantation have increased dramatically over the past 20 years. Cardiovascular disease is the most common extra-hepatic cause of mortality in the long-term post liver transplant. This is intimately linked with both the higher pre-existing rates of metabolic syndrome in these patients as well as increased propensity to develop de novo metabolic syndrome post-transplant. This unfavorable metabolic profile that contributes to cardiovascular disease is multifactorial and largely preventable. This review explores metabolic syndrome and cardiovascular disease and their contributory factors post liver transplantation to highlight areas for potential intervention and thus reduce the significant morbidity and mortality of patients due to metabolic syndrome and cardiovascular disease.
Collapse
|
|
7
|
Sutton TL, Pasko J, Kelly G, Maynard E, Connelly C, Orloff S, Enestvedt CK. Intraoperative autologous transfusion and oncologic outcomes in liver transplantation for hepatocellular carcinoma: a propensity matched analysis. HPB (Oxford) 2022; 24:379-385. [PMID: 34294524 DOI: 10.1016/j.hpb.2021.06.433] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 06/15/2021] [Accepted: 06/29/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Intraoperative autologous transfusion (IAT) of salvaged blood is a common method of resuscitation during liver transplantation (LT), however concern for recurrence in recipients with hepatocellular carcinoma (HCC) has limited widespread adoption. METHODS A review of patients undergoing LT for HCC between 2008 and 2018 was performed. Clinicopathologic and intraoperative characteristics associated with inferior recurrence-free (RFS) and overall survival (OS) were identified using Kaplan-Meier analysis and uni-/multi-variable Cox proportional hazards modeling. Propensity matching was utilized to derive clinicopathologically similar groups for subgroup analysis. RESULTS One-hundred-eighty-six patients were identified with a median follow up of 65 months. Transplant recipients receiving IAT (n = 131, 70%) also had higher allogenic transfusions (median 5 versus 0 units, P < 0.001). There were 14 recurrences and 46 deaths, yielding an estimated 10-year RFS and OS of 89% and 67%, respectively. IAT was not associated with RFS (HR 0.89/liter, P = 0.60), or OS (HR 0.98/liter, P = 0.83) pre-matching, or with RFS (HR 0.97/liter, P = 0.92) or OS (HR 1.04/liter, P = 0.77) in the matched cohort (n = 49 per group). CONCLUSION IAT during LT for HCC is not associated with adverse oncologic outcomes. Use of IAT should be encouraged to minimize the volume of allogenic transfusion in patients undergoing LT for HCC.
Collapse
Affiliation(s)
- Thomas L Sutton
- Oregon Heath & Science University (OHSU), Department of Surgery, Division of General Surgery, Portland, OR, 97239, USA
| | - Jennifer Pasko
- Providence Sacred Heart Medical Center, Liver and Pancreas Surgery, Spokane, WA, 99204, USA
| | | | - Erin Maynard
- OHSU Department of Surgery, Division of Abdominal Organ Transplant and Hepatobiliary Surgery, Portland, OR, 97239, USA
| | - Christopher Connelly
- OHSU Department of Surgery, Division of Abdominal Organ Transplant and Hepatobiliary Surgery, Portland, OR, 97239, USA
| | - Susan Orloff
- OHSU Department of Surgery, Division of Abdominal Organ Transplant and Hepatobiliary Surgery, Portland, OR, 97239, USA
| | - C Kristian Enestvedt
- OHSU Department of Surgery, Division of Abdominal Organ Transplant and Hepatobiliary Surgery, Portland, OR, 97239, USA.
| |
Collapse
|
|
8
|
Fodor M, Woerdehoff A, Peter W, Esser H, Oberhuber R, Margreiter C, Maglione M, Cardini B, Resch T, Weissenbacher A, Sucher R, Zoller H, Tilg H, Öfner D, Schneeberger S. Reassessment of Relevance and Predictive Value of Parameters Indicating Early Graft Dysfunction in Liver Transplantation: AST Is a Weak, but Bilirubin and INR Strong Predictors of Mortality. Front Surg 2021; 8:693288. [PMID: 34869549 PMCID: PMC8634944 DOI: 10.3389/fsurg.2021.693288] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Accepted: 10/27/2021] [Indexed: 01/14/2023] Open
Abstract
Introduction: Early graft dysfunction (EAD) complicates liver transplantation (LT). The aim of this analysis was to discriminate between the weight of each variable as for its predictive value toward patient and graft survival. Methods: We reviewed all LT performed at the Medical University of Innsbruck between 2007 and 2018. EAD was recorded when one of the following criteria was present: (i) aspartate aminotransferase (AST) levels >2,000 IU/L within the first 7 days, (ii) bilirubin levels ≥10mg/dL or (iii) international normalized ratio (INR) ≥1.6 on postoperative day 7. Results: Of 616 LT, 30.7% developed EAD. Patient survival did not differ significantly (P = 0.092; log rank-test = 2.87), graft survival was significantly higher in non-EAD patients (P = 0.008; log rank-test = 7.13). Bilirubin and INR on postoperative day 7 were identified as strong mortality predictors (Bilirubin HR = 1.71 [1.34, 2.16]; INR HR = 2.69 [0.51, 14.31]), in contrast to AST (HR = 0.91 [0.75, 1.10]). Similar results were achieved for graft loss estimation. A comparison with the Model for Early Allograft Function (MEAF) and the Liver Graft Assessment Following Transplantation (L-GrAFT) score identified a superior discrimination potential but lower specificity. Conclusion: Contrarily to AST, bilirubin and INR have strong predictive capacity for patient and graft survival. This fits well with the understanding, that bile duct injury and deprivation of synthetic function rather than hepatocyte injury are key factors in LT.
Collapse
Affiliation(s)
- Margot Fodor
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Adriana Woerdehoff
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Wolfgang Peter
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Hannah Esser
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Rupert Oberhuber
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Christian Margreiter
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Manuel Maglione
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Benno Cardini
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Thomas Resch
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Annemarie Weissenbacher
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Robert Sucher
- Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig, Leipzig, Germany
| | - Heinz Zoller
- Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria
| | - Herbert Tilg
- Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria
| | - Dietmar Öfner
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Stefan Schneeberger
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| |
Collapse
|
|
9
|
Dehghani SM, Shahramian I, Ayatollahi M, Parooie F, Salarzaei M, Bahmanyar M, Sargazi A, Delaramnasab M. The incidence and risk factors of chronic rejection in acutely rejected pediatric liver transplantation. RUSSIAN JOURNAL OF TRANSPLANTOLOGY AND ARTIFICIAL ORGANS 2021; 23:26-31. [DOI: 10.15825/25/1995-1191-2021-4-26-31] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Background. Chronic graft rejection (CR) represents an increasing concern in pediatric liver transplantation (LT). Risk factors of CR in this population are uncertain. In present study, we aimed to ascertain if clinical parameters could predict the occurrence of CR in LT children.Methods. We retrospectively analyzed the results from 47 children who had experienced acute hepatic rejection in Namazee hospital, Shiraz, Iran during 2007–2017.Results. Out of 47 children, 22 (46.8%) and 25 (53.2%) were boys and girls respectively. Ascites, gastrointestinal bleeding, and spontaneous bacterial peritonitis were observed in 20 (44.4%), 14 (31.1%), and 4 (9.1%) respectively. Posttransplant vascular and biliary complications were observed in 3 (7%) and 4 (9.3%) cases respectively. The mean time from LT to normalization of liver enzymes was 14.2 ± 7.5 days. The mean of acute rejection episodes was 1.4 ± 0.6 (median = 1 (22, 46.8%), range of 1–3). Six (12.7%) patients experienced CR. The mean time from LT to CR was 75 ± 28.4 days. A significant association was found between CR and patients’ condition (being inpatient or outpatient) before surgery (P = 0.03). No significant relationship was found between CR and post-transplant parameters except for biliary complications (P = 0.01). Both biliary complication (RR = 33.7, 95% CI: 2.2–511, P = 0.01) and inpatient status (RR = 10.9, 95% CI: 1.1–102.5, P = 0.03) significantly increased the risk of CR.Conclusion. Being hospitalized at the time of LT, and development of biliary complications might predict risk factors for development of CR in LT children.
Collapse
Affiliation(s)
- S. M. Dehghani
- Shiraz Organ Transplantation Center, Nemazee Hospital, Shiraz University of Medical Sciences
| | - I. Shahramian
- Pediatric Gastroenterology and Hepatology Research Center, Zabol University of Medical Science
| | - M. Ayatollahi
- Shiraz Organ Transplantation Center, Nemazee Hospital, Shiraz University of Medical Sciences
| | - F. Parooie
- Pediatric Gastroenterology and Hepatology Research Center, Zabol University of Medical Science
| | - M. Salarzaei
- Pediatric Gastroenterology and Hepatology Research Center, Zabol University of Medical Science
| | | | - A. Sargazi
- Pediatric Gastroenterology and Hepatology Research Center, Zabol University of Medical Science
| | - M. Delaramnasab
- Pediatric Gastroenterology and Hepatology Research Center, Zabol University of Medical Science
| |
Collapse
|
|
10
|
Gitto S, Falcini M, Marra F. Metabolic Disorders After Liver Transplantation. Metab Syndr Relat Disord 2020; 19:65-69. [PMID: 33104408 DOI: 10.1089/met.2020.0068] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Early after surgery, liver transplant (LT) recipients often develop weight gain due to an increase of caloric intake and fat mass (without recovery of muscle frame). This modification of body composition together with a negative metabolic impact of immunosuppressive drugs leads to a high prevalence of all the main metabolic disorders. Indeed, as expected, transplanted patients show a higher cardiovascular risk in comparison with general population. Notably, seeing the increase of mean age of transplanted population, metabolic disorders represent the true challenge for the transplant community. Considering the lack of evidences or clear indications about prevention, early diagnosis and treatment of metabolic disorders after LT, it would be mandatory to develop targeted further studies on this matter.
Collapse
Affiliation(s)
- Stefano Gitto
- Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, University Hospital Careggi, University of Florence, Florence, Italy
| | - Margherita Falcini
- Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, University Hospital Careggi, University of Florence, Florence, Italy
| | - Fabio Marra
- Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, University Hospital Careggi, University of Florence, Florence, Italy
| | | |
Collapse
|
|
11
|
Castelló B, Aguilera V, Blázquez MT, Rubín Á, García M, Vinaixa C, Benlloch S, SanJuan F, Montalva E, López R, Berenguer M. Post-transplantation outcome in non-alcoholic steatohepatitis cirrhosis: Comparison with alcoholic cirrhosis. Ann Hepatol 2020; 18:855-861. [PMID: 31543468 DOI: 10.1016/j.aohep.2019.06.014] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 05/26/2019] [Accepted: 01/29/2019] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Non-alcoholic steatohepatitis (NASH) indication of liver transplant (LT) has increased recently, whereas alcoholic cirrhosis remains a major indication for LT. To characterize NASH-related cases and to compare the post-transplant outcome of these two conditions represents our major objective. MATERIAL AND METHODS Patients undergoing LT for NASH between 1997 and 2016 were retrieved. Those transplanted between 1997 and 2006 were compared to an "age and LT date" matched group of patients transplanted for alcoholic cirrhosis (ratio 1:2). Baseline features and medium-term outcome measures were compared. RESULTS Of 1986 LT performed between 1997 and 2016, 40 (2%) were labeled as NASH-related indications. NASH-related cases increased initially (from 0.8% in 1997-2001 to 2.7% in 2002-2006) but remained stable in subsequent years (2.3%). Hepatocellular carcinoma (HCC) prevalence was greater in NASH-vs alcohol-related cirrhosis (40% vs 3%, p=0.001). The incidence of overweight, obesity, arterial hypertension, dyslipidemia, diabetes, hyperuricemia, renal insufficiency and cardiovascular (CV) disease was similar in both groups at 5 years post-LT. Five-year survival was higher in NASH but without reaching statistical significance (83% vs 72%, p=0.21). The main cause of mortality in NASH-LT patients was HCC recurrence. CONCLUSION Most previously considered cryptogenic cases are actually NASH-cirrhosis. While the incidence of this indication is increasing in many countries, it has remained relatively stable in our Unit, the largest LT center in Spain. HCC is common in these patients and represents a main cause of post-transplant mortality. Metabolic complications, CV-related disease and 5-yr survival do not differ in patients transplanted for NASH vs alcohol.
Collapse
Affiliation(s)
- Beatriz Castelló
- Liver Transplantation and Hepatology Unit, La Fe University Hospital, Valencia, Spain
| | - Victoria Aguilera
- Liver Transplantation and Hepatology Unit, La Fe University Hospital, Valencia, Spain; Networked Biomedical Research Center oh Hepatic and Digestive Diseases, CIBERehd, Spain; Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
| | - M Teresa Blázquez
- Liver Transplantation and Hepatology Unit, La Fe University Hospital, Valencia, Spain
| | - Ángel Rubín
- Liver Transplantation and Hepatology Unit, La Fe University Hospital, Valencia, Spain; Networked Biomedical Research Center oh Hepatic and Digestive Diseases, CIBERehd, Spain; Instituto de Investigación Sanitaria La Fe, Valencia, Spain
| | - María García
- Liver Transplantation and Hepatology Unit, La Fe University Hospital, Valencia, Spain; Networked Biomedical Research Center oh Hepatic and Digestive Diseases, CIBERehd, Spain; Instituto de Investigación Sanitaria La Fe, Valencia, Spain
| | - Carmen Vinaixa
- Liver Transplantation and Hepatology Unit, La Fe University Hospital, Valencia, Spain; Networked Biomedical Research Center oh Hepatic and Digestive Diseases, CIBERehd, Spain; Instituto de Investigación Sanitaria La Fe, Valencia, Spain
| | - Salvador Benlloch
- Liver Transplantation and Hepatology Unit, La Fe University Hospital, Valencia, Spain; Networked Biomedical Research Center oh Hepatic and Digestive Diseases, CIBERehd, Spain; Instituto de Investigación Sanitaria La Fe, Valencia, Spain
| | - Fernando SanJuan
- Liver Transplantation Surgical Unit, La Fe University Hospital, Valencia, Spain
| | - Eva Montalva
- Liver Transplantation Surgical Unit, La Fe University Hospital, Valencia, Spain; Instituto de Investigación Sanitaria La Fe, Valencia, Spain
| | - Rafael López
- Liver Transplantation Surgical Unit, La Fe University Hospital, Valencia, Spain; Instituto de Investigación Sanitaria La Fe, Valencia, Spain
| | - Marina Berenguer
- Liver Transplantation and Hepatology Unit, La Fe University Hospital, Valencia, Spain; Networked Biomedical Research Center oh Hepatic and Digestive Diseases, CIBERehd, Spain; Faculty of Medicine, University of Valencia, Valencia, Spain; Instituto de Investigación Sanitaria La Fe, Valencia, Spain
| |
Collapse
|
|
12
|
Egeli T, Unek T, Ağalar C, Derici S, Ozbilgin M, Akarasu M, Bacakoglu A, Ellidokuz H, Astarcıoglu I. Analysis of Causes and Risk Factors for Late Mortality After Liver Transplant: How Can We Obtain Better Long-Term Survival? EXP CLIN TRANSPLANT 2020; 18:182-187. [PMID: 29863452 DOI: 10.6002/ect.2017.0346] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES We investigated late mortality causes and risk factors in patients who were undergoing deceased-donor liver transplant. MATERIALS AND METHODS Patients who had deceased-donor liver transplant from February 1997 to June 2014 in the hepatopancreaticobiliary surgery and liver transplant unit at Dokuz Eylul University Hospital were analyzed. Inclusion criteria were patients over 18 years of age and who survived more than 1 year after liver transplant. Causes of mortality and related risk factors after the first year were analyzed. RESULTS Of the 157 included patients, 102 patients (72%) received transplant procedures for hepatitis B and C secondary to chronic liver disease. Mean follow-up was 89.85 months (range, 14.4-240 months). Of 157 patients, 20 patients (12.7%) died: 12 patients (60%) died during posttransplant years 2-5 and 8 patients (40%) died after 5 years. Causes of death included malignancy in 8 patients (40%), recurrent hepatitis C infection in 3 patients (15%), infection in 3 patients (15%), coronary artery disease in 2 patients (10%), graft rejection in 2 patients (10%), and biliary complications in 2 patients (10%). Univariate analyses showed that long-term survival was significantly lower in patients older than 50 years (P = .001), when there was presence of hepatocellular carcinoma (P = .011), and when donor age was higher than 38 years (P = .045). Multivariate analyses identified recipient age (P = .007) and presence of hepatocellular carcinoma (P = 0.033) as factors that reduced long-term survival. CONCLUSIONS The main causes of late mortality in liver transplant are malignancy, recurrence of hepatitis C, infection, coronary artery disease, graft rejection, and biliary complications. Advanced age and hepatocellular carcinoma are independent risk factors that increase late mortality.
Collapse
Affiliation(s)
- Tufan Egeli
- >From the Department of General Surgery, Hepatopancreaticobiliary Surgery and Liver Transplantation Unit, Dokuz Eylul University School of Medicine, Narlıdere, Izmir, Turkey
| | | | | | | | | | | | | | | | | |
Collapse
|
|
13
|
Bardou FN, Guillaud O, Erard-Poinsot D, Chambon-Augoyard C, Thimonier E, Vallin M, Boillot O, Dumortier J. Tacrolimus exposure after liver transplantation for alcohol-related liver disease: Impact on complications. Transpl Immunol 2019; 56:101227. [PMID: 31351125 DOI: 10.1016/j.trim.2019.101227] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Revised: 07/16/2019] [Accepted: 07/21/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Alcohol-related liver disease (ALD) is one of the main indications for liver transplantation (LT). For 20 years, tacrolimus (Tac) is the cornerstone immunosuppressive drug used after LT and is very efficient for the prevention of rejection. Nevertheless, the major drawback of long-term use of Tac is the risk for developing dose-dependent adverse effects. OBJECTIVE The aim of the present study was to assess the impact of Tac exposure (trough concentrations and concentration/dose (C/D) ratio) during the first year after LT, on short- and long-term complications after LT for ALD. METHODS All patients who underwent a LT for ALD at Lyon Edouard Herriot Hospital from October 1990 to September 2010, and who were treated with Tac for at least one year after LT, were analyzed. RESULTS The study population consisted in 251 patients, mean age 53.4 ± 7.3 years, and followed during 11.6 ± 4.8 years. Post-LT complications included severe infectious events (44.6%), malignancies (41.4%), arterial hypertension (49.4%) dyslipidemia (44.2%), diabetes (18.7%) and cardiovascular events (15.5%). De novo hypertension, cardiovascular event, CMV infection, non-melanoma skin cancers and HCC recurrence after transplantation were significantly associated with higher Tac trough blood concentration. In addition, Tac fast-metabolizers (defined as C/D < 1.8) had significantly more impaired renal function at 1, 5, and 10 years and more cardiovascular events, PTLD, diabetes and hypertension than slow-metabolizers. CONCLUSION Our results strongly support that, in addition to blood trough concentrations, Tac metabolism, as estimated by the simple C/D ratio, could be an efficient parameter in daily practice to identify LT patients at risk to develop long term general complications of Tac.
Collapse
Affiliation(s)
- Franck-Nicolas Bardou
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | - Olivier Guillaud
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | - Domitille Erard-Poinsot
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | | | - Elsa Thimonier
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | - Mélanie Vallin
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | - Olivier Boillot
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France
| | - Jérôme Dumortier
- Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France.
| |
Collapse
|
|
14
|
Long-term Outcomes and Risk Factors After Adult Living Donor Liver Transplantation. Transplantation 2019; 102:e382-e391. [PMID: 29912047 DOI: 10.1097/tp.0000000000002324] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Although risk factors for the long-term mortality of liver transplantation are well described, there is a lack of detailed study regarding these factors for adult living donor liver transplantation (LDLT). METHODS We retrospectively analyzed 528 adult LDLT recipients in our hospital. The risk factors were analyzed for overall deaths more than 5 years post-LDLT. RESULTS Over the 20-year follow-up, 137 patients died. Patient survival at 1, 3, 5, and 10 years post-LDLT was 87.8%, 81.8%, 79.4%, and 72.8%, respectively. The independent risk factors for more than 5 years post-LDLT overall death were hepatocellular carcinoma recurrence (hazard ratio [HR], 38.9; P < 0.001), lymphoid de novo malignancy (HR, 47.2; P = 0.001), primary sclerosing cholangitis as primary diagnosis (HR, 11.5; P < 0.001), chronic rejection (HR, 6.93; P = 0.006), acute rejection (HR, 2.96; P = 0.017), and bile duct stenosis (HR, 2.30; P = 0.045). CONCLUSIONS Not only malignancies and rejection but also bile duct stenosis and primary sclerosing cholangitis had significant impacts on late period post-LDLT mortality.
Collapse
|
|
15
|
Mu J, Chen Q, Zhu L, Wu Y, Liu S, Zhao Y, Ma T. Influence of gut microbiota and intestinal barrier on enterogenic infection after liver transplantation. Curr Med Res Opin 2019; 35:241-248. [PMID: 29701490 DOI: 10.1080/03007995.2018.1470085] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Liver transplantation is currently a standard therapy for patients with end-stage liver diseases and hepatocellular carcinoma. Given that liver transplantation has undergone a thriving development in these decades, the survival rates after liver transplantation have markedly improved as a result of the critical advancement in surgical techniques, immunosuppressive therapies, and post-operative care. However, infection remains a fatal complication after liver transplantation surgery. In particular, enterogenic infection represents a major complication in liver transplant recipients. This article gives an overview of infection cases after liver transplantation and focuses on the discussion of enterogenic infection in terms of its pathophysiology, risk factor, outcome, and treatment.
Collapse
Affiliation(s)
- Jingzhou Mu
- a College of Basic Medicine , Dalian Medical University , Dalian , Liaoning Province , PR China
| | - Qiuyu Chen
- a College of Basic Medicine , Dalian Medical University , Dalian , Liaoning Province , PR China
| | - Liang Zhu
- a College of Basic Medicine , Dalian Medical University , Dalian , Liaoning Province , PR China
| | - Yunhong Wu
- b College of Public Health , Dalian Medical University , Dalian , Liaoning Province , PR China
| | - Suping Liu
- a College of Basic Medicine , Dalian Medical University , Dalian , Liaoning Province , PR China
| | - Yufei Zhao
- a College of Basic Medicine , Dalian Medical University , Dalian , Liaoning Province , PR China
| | - Tonghui Ma
- a College of Basic Medicine , Dalian Medical University , Dalian , Liaoning Province , PR China
| |
Collapse
|
|
16
|
González JP, Zabaleta A, Sangro P, Basualdo JE, Burgos L, Paiva B, Herrero JI. Immunophenotypic Pattern of De Novo Malignancy After Liver Transplantation. Transplant Proc 2019; 51:77-79. [PMID: 30655139 DOI: 10.1016/j.transproceed.2018.04.090] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Revised: 04/12/2018] [Accepted: 04/27/2018] [Indexed: 10/27/2022]
Abstract
Long-term survival after liver transplantation is affected by de novo neoplasia. The incidence of this type of malignancy is increased in the setting of immunosuppressive therapy. The aim of this study was to characterize the immunologic pattern of liver transplant recipients with de novo malignancies. Fifty-one liver recipients were studied, 19 of whom had a history of de novo neoplasia. Immunophenotypic patterns among patients with/without tumors were compared. The subpopulations of CD4+ T lymphocytes and CD8+ T lymphocytes differed between the 2 types of patients studied. In patients with tumor, activation membrane markers in CD4+ T lymphocytes and CD8+ T-lymphocytes, such as CD56 or CD25, were expressed in a greater proportion, whereas activation markers CD314 and CD16 were reduced in CD56bright natural killer (NK) cells. We concluded that cytotoxic response seems to be more activated in de novo neoplasia patients, which highlights the still unknown malignancy risk effect on these immune cells.
Collapse
Affiliation(s)
- J P González
- School of Medicine, University of Navarra, Pamplona, Navarra, Spain
| | - A Zabaleta
- Flow Cytometry Core, Centro de Investigación Médica Aplicada, Pamplona, Navarra, Spain
| | - P Sangro
- Department of Internal Medicine, Clínica Universidad de Navarra, IDISNA, Pamplona, Navarra, Spain
| | - J E Basualdo
- Liver Unit, Clínica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra and Centro de Investigación Biomédica de enfermedades hepáticas y Digestivas, Pamplona, Navarra, Spain
| | - L Burgos
- Flow Cytometry Core, Centro de Investigación Médica Aplicada, Pamplona, Navarra, Spain
| | - B Paiva
- Flow Cytometry Core, Centro de Investigación Médica Aplicada, Pamplona, Navarra, Spain
| | - J I Herrero
- Department of Internal Medicine, Clínica Universidad de Navarra, IDISNA, Pamplona, Navarra, Spain; Liver Unit, Clínica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra and Centro de Investigación Biomédica de enfermedades hepáticas y Digestivas, Pamplona, Navarra, Spain.
| |
Collapse
|
|
17
|
Zhu A, Leto A, Shaked A, Keating B. Immunologic Monitoring to Personalize Immunosuppression After Liver Transplant. Gastroenterol Clin North Am 2018; 47:281-296. [PMID: 29735024 DOI: 10.1016/j.gtc.2018.01.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Although immunosuppressive drugs have enhanced patient outcomes in transplantation, the liver transplant community has made significant research efforts into the discovery of more accurate and precise methods of posttransplant monitoring and diagnosing. Current research in biomarkers reveals many promising approaches.
Collapse
Affiliation(s)
- Andrew Zhu
- Division of Transplantation, Department of Surgery, Penn Transplant Institute, The University of Pennsylvania, 3400 Spruce Street, Two Dulles Pavilion, Philadelphia, PA 19104, USA
| | - Alexandra Leto
- Division of Transplantation, Department of Surgery, Penn Transplant Institute, The University of Pennsylvania, 3400 Spruce Street, Two Dulles Pavilion, Philadelphia, PA 19104, USA
| | - Abraham Shaked
- Division of Transplantation, Department of Surgery, Penn Transplant Institute, The University of Pennsylvania, 3400 Spruce Street, Two Dulles Pavilion, Philadelphia, PA 19104, USA.
| | - Brendan Keating
- Division of Transplantation, Department of Surgery, Penn Transplant Institute, The University of Pennsylvania, 3400 Spruce Street, Two Dulles Pavilion, Philadelphia, PA 19104, USA
| |
Collapse
|
|
18
|
Busch CJ, Siegler BH, Werle H, Lichtenstern C, Bruckner T, Heininger A, Mehrabi A, Weiss KH, Weigand MA, Hochreiter M. Risk factors for early viral infections after liver transplantation. Langenbecks Arch Surg 2018; 403:509-519. [DOI: 10.1007/s00423-018-1672-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Accepted: 03/28/2018] [Indexed: 12/12/2022]
|
|
19
|
Mücke VT, Gerharz J, Jakobi K, Thomas D, Ferreirós Bouzas N, Mücke MM, Trötschler S, Weiler N, Welker MW, Zeuzem S, Pfeilschifter J, Grammatikos G. Low Serum Levels of (Dihydro-)Ceramides Reflect Liver Graft Dysfunction in a Real-World Cohort of Patients Post Liver Transplantation. Int J Mol Sci 2018; 19:ijms19040991. [PMID: 29587453 PMCID: PMC5979454 DOI: 10.3390/ijms19040991] [Citation(s) in RCA: 7] [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: 02/28/2018] [Revised: 03/19/2018] [Accepted: 03/21/2018] [Indexed: 01/13/2023] Open
Abstract
Patients after orthopic liver transplantation (OLT) are at risk of developing graft dysfunction. Sphingolipids (SL’s) have been identified to play a pivotal role in the regulation of hepatocellular apoptosis, inflammation and immunity. We aimed to investigate the serum SL profile in a prospective real-world cohort of post-OLT patients. From October 2015 until July 2016, 149 well-characterized post-OLT patients were analyzed. SL’s were assessed in serum probes via Liquid Chromatography/Tandem Mass Spectrometry. Twenty-nine (20%) patients had a biopsy proven graft rejection with decreased C20-ceramide (Cer) (p = 0.042), C18-dihydroceramide (DHC) (p = 0.022) and C24DHC (p = 0.060) levels. Furthermore, C18DHC (p = 0.044) and C24DHC (p = 0.011) were significantly down-regulated in patients with ischemic type biliary lesions (ITBL; n = 15; 10%). One-hundred and thirty-three patients (89%) have so far received tacrolimus as the main immunosuppressive agent with observed elevations of C14Cer (p = 0.052), C18Cer (p = 0.049) and C18:1Cer (p = 0.024). Hepatocellular carcinoma (HCC) pre-OLT was associated with increases in C24:1Cer (p = 0.024) and C24:1DHC (p = 0.024). In this large prospective cross-sectional study of patients, post-OLT serum levels of (very-)long chain (dihydro-)ceramides associate with graft rejection, ITBL, tacrolimus intake and HCC pre-OLT. Hence, serum SL’s may be indicative of graft complications. Further research is necessary to identify their diverse mechanistic role in regulating immunity and inflammation in patients post-OLT.
Collapse
Affiliation(s)
- Victoria Therese Mücke
- Universitätsklinikum Frankfurt, Medizinische Klinik 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
| | - Janis Gerharz
- Universitätsklinikum Frankfurt, Medizinische Klinik 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
| | - Katja Jakobi
- Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
| | - Dominique Thomas
- Institut für Klinische Pharmakologie und Toxikologie, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
| | - Nerea Ferreirós Bouzas
- Institut für Klinische Pharmakologie und Toxikologie, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
| | - Marcus Maximilian Mücke
- Universitätsklinikum Frankfurt, Medizinische Klinik 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
| | - Sven Trötschler
- Universitätsklinikum Frankfurt, Medizinische Klinik 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
| | - Nina Weiler
- Universitätsklinikum Frankfurt, Medizinische Klinik 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
| | - Martin-Walter Welker
- Universitätsklinikum Frankfurt, Medizinische Klinik 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
| | - Stefan Zeuzem
- Universitätsklinikum Frankfurt, Medizinische Klinik 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
| | - Josef Pfeilschifter
- Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
- Institut für Klinische Pharmakologie und Toxikologie, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
| | - Georgios Grammatikos
- Universitätsklinikum Frankfurt, Medizinische Klinik 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
- Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
| |
Collapse
|
|
20
|
Moon HH, Kim TS, Song S, Shin M, Chung YJ, Lee S, Choi GS, Kim JM, Kwon CHD, Lee SK, Joh J. Early Vs Late Liver Retransplantation: Different Characteristics and Prognostic Factors. Transplant Proc 2018; 50:2668-2674. [PMID: 30401374 DOI: 10.1016/j.transproceed.2018.03.040] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2018] [Accepted: 03/06/2018] [Indexed: 01/22/2023]
Abstract
BACKGROUND East Asia is a known endemic area for hepatitis B, and living donor liver transplantation is mainly performed. Liver retransplantation (ReLT) is expected to become an increasing problem because of a shortage of organs. This study aimed to compare early and late ReLT with consideration of specific circumstances and disease background of East Asians. METHODS Between October 1996 and January 2015, 51 patients underwent ReLT; we performed a retrospective analysis of data obtained from medical records of the patients. Clinical characteristics, indication, causes of death, survival rate, and prognostic factors were investigated. RESULT The survival rate for early ReLT (n = 18) was 51.5% and that for late ReLT (n = 33) was 50.1% at 1 year postoperatively. Continuous venovenous hemodialysis and the use of mechanical ventilators were more frequent, and pre-retransplant intensive care unit stay and prothrombin time was longer in early ReLT than in late ReLT. Operation time was longer and the amount of intraoperative blood loss was greater in late ReLT than in early ReLT. Multivariate analysis showed that a higher C-reactive protein level increased mortality in early ReLT (P = .045), whereas a higher total bilirubin level increased the risk of death in late ReLT (P = .03). CONCLUSION Patients with early ReLT are likely to be sicker pre-retransplantation and require adequate treatment of the pretransplant infectious disease. On the other hand, late ReLT is likely to be technically more difficult and should be decided before the total bilirubin level increases substantially.
Collapse
Affiliation(s)
- H H Moon
- Department of Surgery, Kosin University Gospel Hospital, Kosin University School of Medicine, Busan, Korea
| | - T-S Kim
- Department of Surgery, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Korea
| | - S Song
- Department of Surgery, Dankuk University Hospital, Dankuk University School of Medicine, Daejeon, Korea
| | - M Shin
- Department of Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
| | - Y J Chung
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - S Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - G S Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - J M Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - C H D Kwon
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - S-K Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - J Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
| |
Collapse
|
|
21
|
Haddad L, Marciano S, Cleres M, Zerega A, Piñero F, Orozco F, Braslavsky G, Mendizabal M, Gondolesi G, Gil O, Silva M, Mastai R, Imventarza O, Descalzi V, Gadano A. Characteristics of Liver Transplantation in Argentina: A Multicenter Study. Transplant Proc 2018; 50:478-484. [PMID: 29579832 DOI: 10.1016/j.transproceed.2017.11.072] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2017] [Accepted: 11/11/2017] [Indexed: 11/16/2022]
Abstract
INTRODUCTION There is a lack of information regarding outcomes after liver transplant in Latin America. OBJECTIVES This study sought to describe outcomes after liver transplant in adult patients from Argentina. METHODS We performed an ambispective cohort study of adult patients transplanted between June 2010 and October 2012 in 6 centers from Argentina. Only patients who survived after the first 48 hours postransplantation were included. Pretransplantation and posttransplantation data were collected. RESULTS A total of 200 patients were included in the study. Median age at time of transplant was 50 (interquartile range [IQR] 26 to 54) years. In total, 173 (86%) patients had cirrhosis, and the most frequent etiology in these patients was hepatitis C (32%). A total of 35 (17%) patients were transplanted with hepatocellular carcinoma. In patients with cirrhosis, the median Model for End-Stage Liver Disease (MELD) score at time of liver transplant was 25 (IQR 19 to 30). Median time on the waiting list for elective patients was 101 (IQR 27 to 295) days, and 3 (IQR 2 to 4) days for urgent patients. Almost 40% of the patients were readmitted during the first 6 months after liver transplant. Acute rejection occurred in 27% of the patients. Biliary and vascular complications were reported in 39 (19%) and 19 (9%) patients, respectively. Renal failure, diabetes, and dyslipidemia were present in 40 (26%), 87 (57%), and 77 (50%) at 2 years, respectively. CONCLUSIONS We believe the information contained in this article might be of value for reviewing current practices and developing local policies.
Collapse
Affiliation(s)
- L Haddad
- Sección Hepatología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
| | - S Marciano
- Departamento de Investigación, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - M Cleres
- Unidad de hepatología y Trasplante Hepático, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina
| | - A Zerega
- Unidad de Trasplante Hepático, Sanatorio Allende, Córdoba, Argentina
| | - F Piñero
- Unidad de Hígado y Trasplante Hepático, Hospital Universitario Austral, Buenos Aires, Argentina
| | - F Orozco
- Unidad de Trasplante Hepático Hospital Alemán, Buenos Aires, Argentina
| | - G Braslavsky
- Unidad de Trasplante Hepático Hospital Dr. Cosme Argerich, Buenos Aires, Argentina
| | - M Mendizabal
- Unidad de Hígado y Trasplante Hepático, Hospital Universitario Austral, Buenos Aires, Argentina
| | - G Gondolesi
- Unidad de hepatología y Trasplante Hepático, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina
| | - O Gil
- Unidad de Trasplante Hepático, Sanatorio Allende, Córdoba, Argentina
| | - M Silva
- Unidad de Hígado y Trasplante Hepático, Hospital Universitario Austral, Buenos Aires, Argentina
| | - R Mastai
- Unidad de Trasplante Hepático Hospital Alemán, Buenos Aires, Argentina
| | - O Imventarza
- Unidad de Trasplante Hepático Hospital Dr. Cosme Argerich, Buenos Aires, Argentina
| | - V Descalzi
- Unidad de hepatología y Trasplante Hepático, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina
| | - A Gadano
- Sección Hepatología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| |
Collapse
|
|
22
|
Kappus M, Abdelmalek M. De Novo and Recurrence of Nonalcoholic Steatohepatitis After Liver Transplantation. Clin Liver Dis 2017; 21:321-335. [PMID: 28364816 DOI: 10.1016/j.cld.2016.12.006] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developing countries. Approximately 25% of patients with NAFLD develop nonalcoholic steatohepatitis (NASH). NASH-related cirrhosis is now a leading listing indication for liver transplantation in the United States. Although posttransplant survival for NASH-related cirrhosis is comparable with that of other liver diseases, many patients have features of metabolic syndrome, which can contribute to a recurrence of NAFLD or NASH. This article reviews the epidemiology, pathophysiology, and treatment of de novo and recurrence of NASH after liver transplantation.
Collapse
Affiliation(s)
- Matthew Kappus
- Division of Gastroenterology, Duke University Medical Center, 40 Duke Medicine Circle, PO Box 3913, Durham, NC 27710, USA
| | - Manal Abdelmalek
- Division of Gastroenterology, Duke University Medical Center, 40 Duke Medicine Circle, PO Box 3913, Durham, NC 27710, USA.
| |
Collapse
|
|
23
|
Buescher N, Seehofer D, Helbig M, Andreou A, Bahra M, Pascher A, Pratschke J, Schoening W. Evaluating twenty-years of follow-up after orthotopic liver transplantation, best practice for donor-recipient matching: What can we learn from the past era? World J Transplant 2016; 6:599-607. [PMID: 27683639 PMCID: PMC5036130 DOI: 10.5500/wjt.v6.i3.599] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 05/18/2016] [Accepted: 08/01/2016] [Indexed: 02/05/2023] Open
Abstract
AIM To characterize major determinants of 20-year survival after liver transplantation (LT).
METHODS This longitudinal single-institution study includes 313 consecutive patients who received a LT between 1988 and 1992. Pretransplant clinical characteristics and laboratory values were assessed and compared between 20-year survivors and non-survivors. Particular attention was paid to the Model for End-Stage Liver Disease (labMELD)-score and the Eurotransplant Donor Risk Index (ET-DRI) to unravel their impact on 20-year survival after LT.
RESULTS Twenty-year survivors were significantly younger (44 vs 50 years, P = 0.001), more likely to be female (49% vs 36%, P = 0.03) and less likely to be obese at the time of LT (19% vs 32%, P = 0.011). Mean labMELD-score (P = 0.156), rate of high-urgency LT (P = 0.210), cold-ischemia time (P = 0.994), rate of retransplantation (P = 0.12) and average donor age (28 vs 33 years, P = 0.099) were not statistically different. The mean estimated glomerular filtration rate was higher among survivors (P = 0.007). ET-DRI > 1.4 (P = 0.020) and donor age ≥ 30 years (P < 0.022) had significant influence on 20-year survival. The overall survival was not significantly impacted by labMELD-score categories (P = 0.263).
CONCLUSION LT offers excellent long-term results in case of optimal donor and recipient conditions. However, mainly due to the current organ shortage, these ideal circumstances are rarely given; thus algorithms for donor-recipient matching need to be refined, in order to enable a maximum benefit for the recipients of high quality as well as marginal organs.
Collapse
|
|
24
|
Harrington PB, McAlexander WW, Bryant AS, Wallace P, Massey J, Gray S, Kukreja M, Cleveland DC, Kirklin JK, Davies JE. Outcomes of Patients Who Undergo Cardiac Surgical Procedures After Liver Transplantation. Ann Thorac Surg 2016; 103:541-545. [PMID: 27623271 DOI: 10.1016/j.athoracsur.2016.06.023] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Revised: 06/07/2016] [Accepted: 06/13/2016] [Indexed: 01/14/2023]
Abstract
BACKGROUND There is a paucity of information available regarding the impact of cardiac surgical procedures on patients who have undergone previous liver transplantation. The primary purpose of this study was to ascertain the survival rate and predictors of death in this specific patient population. METHODS This retrospective cohort study consisted of a consecutive series of patients with a functioning liver allograft who subsequently underwent cardiac surgical procedures between January 1991 and December 2012. The optimal Model for End-Stage Liver Disease (MELD) score for predicting late death was identified using receiver operating characteristic curve analysis. Risk of postoperative death was determined by parametric hazard analysis. RESULTS Between January 1991 and December 2012, 43 patients (median age, 60 years) underwent cardiac surgical procedures after liver transplantation. The median interval between liver transplant and cardiac operation was 63 months (range, 1.1 to 217 months). Three operative deaths and 24 late deaths occurred. Receiver operating characteristic curve analysis identified the optimal preoperative and postoperative MELD score cut points for predicting late death as greater than 13.8 (area under the curve = 0.674) and greater than 17 (area under the curve = 0.633), respectively. Patients with a preoperative MELD score of 13.8 or less had significantly greater survival rates than those with a MELD score greater than 13.8 (p = 0.028); patients with a postoperative MELD score of 17 of less had significantly greater survival rates than those with a MELD score greater than 17 (p < 0.001). Multivariate parametric hazard analysis identified postoperative peak creatinine level as a statistically significant predictor of death (relative risk, 1.8; p = 0.01). The 1-, 5-, and 10-year Kaplan-Meier survival rates were 90%, 51%, and 35%, respectively; postoperative mortality rates followed a constant phase model with a hazard of death of 10% per year. CONCLUSIONS Cardiac surgical procedures can be performed with acceptable short-term and long-term outcomes in liver transplant recipients. Elevated preoperative and postoperative MELD scores and postoperative peak creatinine level may portend death in this cohort. There is a constant hazard of death of 10% per year.
Collapse
Affiliation(s)
- Phillips B Harrington
- Division of Cardiothoracic Surgery, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama.
| | - William W McAlexander
- Division of Cardiothoracic Surgery, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama
| | - Ayesha S Bryant
- Division of Cardiothoracic Surgery, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama
| | - Payden Wallace
- University of Alabama at Birmingham School of Medicine, Birmingham, Alabama
| | - Julia Massey
- University of Alabama at Birmingham School of Medicine, Birmingham, Alabama
| | - Stephen Gray
- Division of Abdominal Transplantation, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama
| | - Manish Kukreja
- Division of Cardiothoracic Surgery, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama
| | - David C Cleveland
- Division of Cardiothoracic Surgery, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama
| | - James K Kirklin
- Division of Cardiothoracic Surgery, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama
| | - James E Davies
- Division of Cardiothoracic Surgery, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama
| |
Collapse
|
|
25
|
Early Predictors of Long-term Outcomes of HCV-negative Liver Transplant Recipients Having Survived the First Postoperative Year. Transplantation 2016; 100:382-90. [PMID: 26683515 DOI: 10.1097/tp.0000000000001038] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND The non-improvement in >1-year post-liver transplant (LT) survival and diminishing importance of hepatitis C (HCV) with modern antivirals justify identification of early factors predictive of long-term outcome post-LT in HCV-negative recipients. METHODS This nationwide study included all 631 HCV-negative adult patients transplanted in Finland 1982-2013 with at least 1-year graft survival (6311 person-year follow-up). We tested 37 variables, including immunosuppression, for their association with >1-year combined graft loss/mortality, late rejection, cancer, or infections. RESULTS Significant multivariate predictors of graft loss/mortality were male gender (HR 2.40, P = 0.001), pretransplant hepatocellular (HR 2.92, P = 0.001) or biliary cancer (HR 12.7, P < 0.001), glomerular filtration rate (HR 0.89, P = 0.002), hypertension (HR 0.44, P < 0.001), early posttransplant infections (HR 1.52-1.67, P = 0.007-0.03), and alkaline phosphatase (ALP) (HR 1.05, P < 0.001). Elevated ALP at 1 year, affecting 30% of patients, predicted both graft loss and rejection, independent of immunologic stability, etiology, and immunosuppression type. Area under the curve of ALP in predicting graft loss from rejection was 0.81 (95% CI 0.71-0.90) and 0.85 (95% CI 0.72-0.98, P = 0.001) among patients under 50. Among immunologically stable patients who underwent transplantation after 2000, antimetabolite use at 1 year was associated with improved survival (P = 0.04), specifically in the subgroup with native-liver hepatocellular or biliary cancer (P = 0.02). CONCLUSIONS Easily measurable, widely available, and noninvasive factors known at 1 year post-LT can help stratify patients according to their long-term risk of death or graft loss, and thus facilitate a personalization of long-term follow-up. ALP deserves routine monitoring, and the cause for an elevated ALP should be sought.
Collapse
|
|
26
|
Gitto S, Vukotic R, Vitale G, Pirillo M, Villa E, Andreone P. Non-alcoholic steatohepatitis and liver transplantation. Dig Liver Dis 2016; 48:587-591. [PMID: 27038703 DOI: 10.1016/j.dld.2016.02.014] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2015] [Revised: 01/22/2016] [Accepted: 02/23/2016] [Indexed: 02/08/2023]
Abstract
Non-alcoholic steatohepatitis is a growing liver-related health problem. In Europe, non-alcoholic fatty liver disease is the most usual reason of chronic liver illness while steatohepatitis, its progressive form, affects 1% of Europeans and North Americans. In the United States steatohepatitis-related cirrhosis is one of the main indications for liver transplant. A targeted stratification for patients waiting for transplant and affected by this disease is mandatory especially because of their increased cardiovascular and cancer risk. The adequate treatment of NAFLD is crucial for the reduction of the disease related morbidity and mortality. In post-transplant setting, the recurrent or de novo steatosis might seriously affect the allograft short- and long-term outcome. Many conditions can represent the basis of the post-transplant steatohepatitis: obesity, hyperlipidaemia, diabetes mellitus, arterial hypertension, immunosuppressant treatment, alcoholic habit and liver graft steatosis. Today, the only consolidated therapy is represented by a deep life-style intervention since the use of drug-based alternative strategies is still limited and a very few data are available for the post-transplant period. Targeted and personalized behaviour and pharmacological interventions have to be developed for both the pre- and post-transplant phase.
Collapse
Affiliation(s)
- Stefano Gitto
- Department of Gastroenterology, Azienda Ospedaliero-Universitaria and University of Modena and Reggio Emilia, Modena, Italy
| | - Ranka Vukotic
- Dipartimento di Scienze Mediche e Chirurgiche, Centro Studi e Ricerche sulle Epatiti, Alma Mater Studiorum, Univesity of Bologna, Bologna, Italy
| | - Giovanni Vitale
- Dipartimento di Scienze Mediche e Chirurgiche, Centro Studi e Ricerche sulle Epatiti, Alma Mater Studiorum, Univesity of Bologna, Bologna, Italy
| | - Martina Pirillo
- Dipartimento di Scienze Mediche e Chirurgiche, Centro Studi e Ricerche sulle Epatiti, Alma Mater Studiorum, Univesity of Bologna, Bologna, Italy
| | - Erica Villa
- Department of Gastroenterology, Azienda Ospedaliero-Universitaria and University of Modena and Reggio Emilia, Modena, Italy
| | - Pietro Andreone
- Dipartimento di Scienze Mediche e Chirurgiche, Centro Studi e Ricerche sulle Epatiti, Alma Mater Studiorum, Univesity of Bologna, Bologna, Italy.
| |
Collapse
|
|
27
|
Kahn A, Reynolds JA, Chakkera HA, Aqel BA, Byrne TJ, Douglas DD, Moss AA, Vargas HE, Carey EJ. Prospective Analysis of Metabolic Parameters in the Detection of Diabetes and Metabolic Syndrome in Liver Transplant Recipients. Metab Syndr Relat Disord 2016; 14:305-10. [PMID: 27164306 DOI: 10.1089/met.2015.0162] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Liver transplant recipients are at increased risk of metabolic complications, including new-onset diabetes mellitus after transplantation (NODAT) and post-transplant metabolic syndrome (PTMS), both of which are associated with decreased patient survival. We prospectively monitored traditional and novel metabolic parameters in nondiabetic liver transplantation (LT) candidates to determine their role in detecting these conditions. METHODS Nondiabetic adults undergoing initial LT were prospectively identified. NODAT and PTMS were defined according to WHO and ATP III criteria. Metabolic measures were collected at pre-LT, 4, and 12 months post-LT. RESULTS Of 49 subjects enrolled, 24.5% were found to be diabetic pre-LT by 2-hr oral glucose tolerance test (OGTT) despite fasting glucose below the diabetic range. Two patients developed NODAT post-LT. A single patient was found to have MS at baseline, while PTMS developed in 26% and 31.3% of patients at 4 and 12 months. Novel metabolic markers did not detect these conditions. CONCLUSIONS Screening OGTT detected pre-LT diabetes in patients with normal fasting glucose. Serial measurement of metabolic parameters allowed earlier detection of PTMS. Novel metabolic parameters did not correspond to post-LT outcomes, but provided a baseline for future study. More frequent and intensive metabolic monitoring appears reasonable, but larger studies are needed to clarify its efficacy.
Collapse
Affiliation(s)
- Allon Kahn
- 1 Department of Medicine, Mayo Clinic , Phoenix, Arizona
| | - Justin A Reynolds
- 2 Center for Liver and Hepatobiliary Disease, St. Joseph's Hospital and Medical Center , Phoenix, Arizona
| | | | - Bashar A Aqel
- 4 Division of Gastroenterology and Hepatology, Mayo Clinic , Phoenix, Arizona
| | - Thomas J Byrne
- 4 Division of Gastroenterology and Hepatology, Mayo Clinic , Phoenix, Arizona
| | - David D Douglas
- 4 Division of Gastroenterology and Hepatology, Mayo Clinic , Phoenix, Arizona
| | - Adyr A Moss
- 5 Division of Transplant Surgery, Mayo Clinic , Phoenix, Arizona
| | - Hugo E Vargas
- 4 Division of Gastroenterology and Hepatology, Mayo Clinic , Phoenix, Arizona
| | - Elizabeth J Carey
- 4 Division of Gastroenterology and Hepatology, Mayo Clinic , Phoenix, Arizona
| |
Collapse
|
|
28
|
Tong MS, Chai HT, Liu WH, Chen CL, Fu M, Lin YH, Lin CC, Chen SM, Hang CL. Prevalence of hypertension after living-donor liver transplantation: a prospective study. Transplant Proc 2015; 47:445-50. [PMID: 25769588 DOI: 10.1016/j.transproceed.2014.10.050] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2014] [Revised: 10/10/2014] [Accepted: 10/28/2014] [Indexed: 12/17/2022]
Abstract
BACKGROUND Hypertension is common among patients who have undergone liver transplantation and is a major contributor to cardiovascular events. Few studies have studied the risk factors associated with post-liver transplantation (LT) hypertension. This prospective study assessed the prevalence of post-LT hypertension and associated preoperative risk factors. METHODS From May 2008 to December 2009, 79 normotensive adult patients (≥ 18 years old) who underwent living-donor LT with a median follow up of 4.79 ± 0.88 years were enrolled. Patients' pre-LT demographics, clinical data, pre-LT diabetes, and immunosuppressive agents used after LT were studied for their association with post-LT hypertension. RESULTS The prevalence of post-LT hypertension was 49.4%. The independent risk factors for post-living-donor LT hypertension were pre-LT systolic blood pressure (SBP; odds ratio [OR], 1.04; 95% confidence interval [CI], 1.00-1.09; P = .039) and post-LT administration of mammalian target of rapamycin (mTOR) inhibitors (OR, 4.08; 95% CI, 1.40-11.94; P = .010). Pre-LT diabetes had a negative predictive value (OR, 0.15; 95% CI, 0.03-0.74; P = .019). Neither age, male sex, smoking, pre-LT serum cholesterol and triglyceride levels, tacrolimus, nor glucocorticoid was associated with post-LT hypertension. CONCLUSIONS The prevalence of hypertension is high after LT. Higher pre-LT SBP and post-LT mTOR inhibitor administration predispose patients to post-LT hypertension.
Collapse
Affiliation(s)
- M-S Tong
- Section of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan, Republic of China; Chang Gung University College of Medicine, Kaohsiung City, Taiwan, Republic of China
| | - H-T Chai
- Section of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan, Republic of China; Chang Gung University College of Medicine, Kaohsiung City, Taiwan, Republic of China
| | - W-H Liu
- Section of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan, Republic of China; Chang Gung University College of Medicine, Kaohsiung City, Taiwan, Republic of China
| | - C-L Chen
- Chang Gung University College of Medicine, Kaohsiung City, Taiwan, Republic of China; Liver Transplantation Program, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan, Republic of China
| | - M Fu
- Section of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan, Republic of China; Chang Gung University College of Medicine, Kaohsiung City, Taiwan, Republic of China
| | - Y-H Lin
- Chang Gung University College of Medicine, Kaohsiung City, Taiwan, Republic of China; Liver Transplantation Program, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan, Republic of China
| | - C-C Lin
- Chang Gung University College of Medicine, Kaohsiung City, Taiwan, Republic of China; Liver Transplantation Program, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan, Republic of China
| | - S-M Chen
- Section of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan, Republic of China.
| | - C-L Hang
- Section of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan, Republic of China; Chang Gung University College of Medicine, Kaohsiung City, Taiwan, Republic of China
| |
Collapse
|
|
29
|
Hara Y, Kawagishi N, Nakanishi W, Tokodai K, Nakanishi C, Miyagi S, Ohuchi N. Prevalence and risk factors of obesity, hypertension, dyslipidemia and diabetes mellitus before and after adult living donor liver transplantation. Hepatol Res 2015; 45:764-70. [PMID: 25196899 DOI: 10.1111/hepr.12418] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2014] [Revised: 08/30/2014] [Accepted: 09/02/2014] [Indexed: 02/08/2023]
Abstract
AIM The development of metabolic abnormalities after liver transplantation (LTx) contributes to cardiovascular events and mortality. We analyzed the prevalence and risk factors of obesity, hypertension, dyslipidemia and diabetes mellitus (DM) after adult living donor liver transplantation. METHODS Fifty-four adult recipients with a minimum follow up of 6 months receiving living donor liver transplantation between 2001 and 2012 at the Tohoku University Hospital were retrospectively analyzed. RESULTS The prevalence of hypertension increased from 18.5% before transplantation to 35.2% post-transplantation, and new-onset hypertension after transplantation was 57.9% of post-transplant hypertension. Univariate analysis showed that risk factors of post-transplant hypertension were age (>50 years, P = 0.0023), pretransplant body mass index (BMI) of 25 or more (P = 0.0123), pretransplant hypertension (P = 0.0012) and cyclosporin A (61.5% vs tacrolimus 25.0%, P = 0.0248). The incidence of obesity, dyslipidemia and DM did not change from before to after transplantation. LTx was curative in 77.8% of cases of pretransplant dyslipidemia and 20% of cases of pretransplant DM. Primary biliary cirrhosis cases comprised 85.7% of cases of pretransplant dyslipidemia that were cured by LTx. In univariate analysis, pretransplant BMI of 25 or more was the only risk factor of post-transplant dyslipidemia (P = 0.0098). The incidence of new-onset DM after transplantation was 20%. Risk factors of post-transplant DM were male sex (P = 0.0156), pretransplant DM (P < 0.0001), alcohol abuse (P = 0.0248) and mycophenolate mofetil (P = 0.0181) by univariate analysis. CONCLUSION The prevalence of hypertension increased after LTx and pretransplant obesity was associated with several post-transplant metabolic abnormalities.
Collapse
Affiliation(s)
- Yasuyuki Hara
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Naoki Kawagishi
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Wataru Nakanishi
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Kazuaki Tokodai
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Chikashi Nakanishi
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Shigehito Miyagi
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Noriaki Ohuchi
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
| |
Collapse
|
|
30
|
Wei W, Huang XH, Liang D, Zeng YY, Ma C, Wu YB, Li YT, Zhang X, Zeng JH, Liu JF. A proteomic analysis of transplanted liver in a rat model of chronic rejection. Clin Res Hepatol Gastroenterol 2015; 39:340-350. [PMID: 25468549 DOI: 10.1016/j.clinre.2014.10.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2014] [Revised: 07/29/2014] [Accepted: 10/03/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND Chronic rejection (CR) is an important cause of liver allograft failure. In the latter condition, re-transplantation of the liver (ReLT) is the only option for survival. Unfortunately, with the current state of knowledge, it is difficult to diagnose and treat early CR. OBJECTIVE To explore the biomarkers of the chronic rejection in orthotopic liver transplantation (OLT). METHODS A rat model of chronic liver allograft rejection was established, and the differential protein expression in chronic allograft rejection (CR) was analyzed by iTRAQ-MALDI-TOF/TOF. RESULTS Expression of sixty-two proteins was found to be significantly changed in CR rats. In the present study, CLU, Lcn2 and Krt19 were identified and quantified as early and reliable biomarkers for chronic rejection. CONCLUSION Analysis of differential protein expression by iTRAQ-MALDI-TOF/TOF is a potentially effective method to help understand the mechanism of CR in orthotopic liver transplantation. The proteins CLU, Lcn2 and Krt19 might be potential prognostic markers for predicting chronic rejection after liver transplantation.
Collapse
Affiliation(s)
- Wei Wei
- The First Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
| | - Xin-Hui Huang
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Dong Liang
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Yong-Yi Zeng
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Chuang Ma
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Yan-Bin Wu
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Yun-Tong Li
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Xiang Zhang
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Jin-Hua Zeng
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Jing-Feng Liu
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
| |
Collapse
|
|
31
|
Di Maira T, Rubin A, Puchades L, Aguilera V, Vinaixa C, Garcia M, De Maria N, Villa E, Lopez-Andujar R, San Juan F, Montalva E, Perez J, Prieto M, Berenguer M. Framingham score, renal dysfunction, and cardiovascular risk in liver transplant patients. Liver Transpl 2015; 21:812-22. [PMID: 27396823 DOI: 10.1002/lt.24128] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2014] [Revised: 03/11/2015] [Accepted: 03/14/2015] [Indexed: 12/12/2022]
Abstract
Cardiovascular (CV) events represent major impediments to the long-term survival of liver transplantation (LT) patients. The aim of this study was to assess whether the Framingham risk score (FRS) at transplantation can predict the development of post-LT cardiovascular events (CVEs). Patients transplanted between 2006 and 2008 were included. Baseline features, CV risk factors, and CVEs occurring after LT (ischemic heart disease, stroke, heart failure, de novo arrhythmias, and peripheral arterial disease) were recorded. In total, 250 patients (69.6% men) with a median age of 56 years (range, 18-68 years) were included. At transplantation, 34.4%, 34.4%, and 33.2% of patients, respectively, had a low, moderate, and high FRS with a median FRS of 14.9 (range, 0.09-30); 14.4% of LT recipients developed at least 1 CVE at a median of 2.619 years (range, 0.006-6.945 years). In the univariate analysis, factors associated with the development of CVEs were the continuous FRS at LT (P = 0.003), age (P = 0.007), creatinine clearance [estimated glomerular filtration rate (eGFR); P = 0.020], and mycophenolate mofetil use at discharge (P = 0.011). In the multivariate analysis, only the eGFR [hazard ratio (HR), 0.98; 95% confidence interval (CI), 0.97-1.00; P = 0.009] and FRS (HR, 1.06; 95% CI, 1.02-1.10; P = 0.002) remained in the model. Moreover, an association was also found between the FRS and overall survival (P = 0.004) with 5-year survival rates of 82.5%, 77.8%, and 61.4% for the low-, moderate-, and high-risk groups, respectively. Continuous FRS, eGFR, and hepatitis C virus infection were independent risk factors for overall mortality. In our series, the FRS and eGFR at LT were able to predict the development of post-LT CVEs and poor outcomes. Liver Transpl 21:812-822, 2015. © 2015 AASLD.
Collapse
Affiliation(s)
- Tommaso Di Maira
- Liver Transplantation and Hepatology Unit, La Fe Hospital, Valencia, Spain.,Gastroenterology Unit, Azienda Ospedaliero-Universitaria, University of Modena and Reggio Emilia, Modena, Italy
| | - Angel Rubin
- Liver Transplantation and Hepatology Unit, La Fe Hospital, Valencia, Spain
| | - Lorena Puchades
- Liver Transplantation and Hepatology Unit, La Fe Hospital, Valencia, Spain
| | - Victoria Aguilera
- Liver Transplantation and Hepatology Unit, La Fe Hospital, Valencia, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Valencia, Spain
| | - Carmen Vinaixa
- Liver Transplantation and Hepatology Unit, La Fe Hospital, Valencia, Spain
| | - Maria Garcia
- Liver Transplantation and Hepatology Unit, La Fe Hospital, Valencia, Spain
| | - Nicola De Maria
- Gastroenterology Unit, Azienda Ospedaliero-Universitaria, University of Modena and Reggio Emilia, Modena, Italy
| | - Erica Villa
- Gastroenterology Unit, Azienda Ospedaliero-Universitaria, University of Modena and Reggio Emilia, Modena, Italy
| | - Rafael Lopez-Andujar
- Hepatic Surgery and Liver Transplant Unit, and, La Fe University Hospital, Valencia, Spain
| | - Fernando San Juan
- Hepatic Surgery and Liver Transplant Unit, and, La Fe University Hospital, Valencia, Spain
| | - Eva Montalva
- Hepatic Surgery and Liver Transplant Unit, and, La Fe University Hospital, Valencia, Spain
| | - Judith Perez
- Department of Pathology and Anatomy, La Fe University Hospital, Valencia, Spain
| | - Martin Prieto
- Liver Transplantation and Hepatology Unit, La Fe Hospital, Valencia, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Valencia, Spain
| | - Marina Berenguer
- Liver Transplantation and Hepatology Unit, La Fe Hospital, Valencia, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Valencia, Spain.,Faculty of Medicine, University of Valencia, Valencia, Spain
| |
Collapse
|
|
32
|
Åberg F, Gissler M, Karlsen TH, Ericzon BG, Foss A, Rasmussen A, Bennet W, Olausson M, Line PD, Nordin A, Bergquist A, Boberg KM, Castedal M, Pedersen CR, Isoniemi H. Differences in long-term survival among liver transplant recipients and the general population: a population-based Nordic study. Hepatology 2015; 61:668-677. [PMID: 25266201 DOI: 10.1002/hep.27538] [Citation(s) in RCA: 102] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2014] [Accepted: 09/25/2014] [Indexed: 12/11/2022]
Abstract
UNLABELLED Dramatic improvement in first-year outcomes post-liver transplantation (LT) has shifted attention to long-term survival, where efforts are now needed to achieve improvement. Understanding the causes of premature death is a prerequisite for improving long-term outcome. Overall and cause-specific mortality of 3,299 Nordic LT patients (1985-2009) having survived 1 year post-LT were divided by expected rates in the general population, adjusted for age, sex, calendar date, and country to yield standardized mortality ratios (SMRs). Data came from the Nordic Liver-Transplant Registry and WHO mortality-indicator database. Stagnant patient survival rates >1 year post-LT were 21% lower at 10 years than expected survival for the general population. Overall SMR for death before age 75 (premature mortality) was 5.8 (95% confidence interval [CI] 5.4-6.3), with improvement from 1985-1999 to 2000-2010 in hepatitis C (HCV) (SMR change 23.1-9.2), hepatocellular carcinoma (HCC) (SMR 38.4-18.8), and primary sclerosing cholangitis (SMR 11.0-4.2), and deterioration in alcoholic liver disease (8.3-24.0) and acute liver failure (ALF) (5.9-7.6). SMRs for cancer and liver disease (recurrent or transplant-unrelated disease) were elevated in all indications except primary biliary cirrhosis (PBC). Absolute mortality rates underestimated the elevated premature mortality from infections (SMR 22-693) and kidney disease (SMR 13-45) across all indications, and from suicide in HCV and ALF. SMR for cardiovascular disease was significant only in PBC and alcoholic liver disease, owing to high mortality in the general population. Transplant-specific events caused 16% of deaths. CONCLUSION standardized premature mortality provided an improved picture of long-term post-LT outcome, showing improvement over time in some indications, not revealed by overall absolute mortality rates. Causes with high premature mortality (infections, cancer, kidney and liver disease, and suicide) merit increased attention in clinical patient follow-up and future research.
Collapse
Affiliation(s)
- Fredrik Åberg
- Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland; Department of Gastroenterology, Helsinki University Hospital, Helsinki, Finland
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
33
|
Xi ZF, Xia Q. Recent advances in prevention of hepatitis B recurrence after liver transplantation. World J Gastroenterol 2015; 21:829-835. [PMID: 25624716 PMCID: PMC4299335 DOI: 10.3748/wjg.v21.i3.829] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2014] [Revised: 08/31/2014] [Accepted: 12/08/2014] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation is the only effective treatment for hepatitis B virus (HBV)-related end-stage liver disease. However, without antiviral prophylaxis, the recurrence rate of hepatitis B is as high as 80%-100%, which leads to a 50% mortality rate in the first 2 years after liver transplantation. Combination therapy of hepatitis B immunoglobulin (HBIG) and lamivudine demonstrated a higher efficacy of prophylaxis and further reduced the rate of recurrence to < 10%. The strategy of HBIG combined with lamivudine has been the standard treatment in many centers. However, the high rate of lamivudine resistance and the many disadvantages of HBIG have compelled surgeons to reconsider the long-term efficacy of this strategy for the prevention of HBV reinfection. Recently, new nucleos(t)ide analogues, such as entecavir and tenofovir, have been approved as first-line monotherapies for the treatment of chronic hepatitis B infection. These antiviral medicines have replaced lamivudine as the first choice in the prevention of HBV recurrence after liver transplantation. Various therapies that are composed of entecavir, tenofovir, and lamivudine plus adefovir, with or without HBIG have been adopted in several liver transplant centers. This article reviews the recent advances in prophylaxis for the recurrence of hepatitis B after liver transplantation.
Collapse
|
|
34
|
Katoonizadeh A, Poustchi H, Malekzadeh R. Hepatic progenitor cells in liver regeneration: current advances and clinical perspectives. Liver Int 2014; 34:1464-1472. [PMID: 24750779 DOI: 10.1111/liv.12573] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2013] [Accepted: 04/17/2014] [Indexed: 12/12/2022]
Abstract
When there is a massive loss of hepatocytes and/or an inhibition in the proliferative capacity of the mature hepatocytes, activation of a dormant cell population of resident hepatic progenitor cells (HPCs) occurs. Depending on the type of liver damage HPCs generate new hepatocytes and biliary cells to repopulate the liver placing them as potential candidates for cell therapy in human liver failure. Liver injury specific mechanisms through which HPCs differentiate towards mature epithelial cell types are recently become understood. Such new insights will enable us not only to direct HPCs behaviour for therapeutic purposes, but also to develop clinically feasible methods for in vivo differentiation of other stem cell types towards functional hepatocytes. This review aimed to provide the current improved knowledge of the role of HPCs niche and its signals in directing the behaviour and fate of HPCs and to translate this basic knowledge of HPCs activation/differentiation into its clinical applications.
Collapse
Affiliation(s)
- Aezam Katoonizadeh
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | | | | |
Collapse
|
|
35
|
Dopazo C, Bilbao I, Castells LL, Sapisochin G, Moreiras C, Campos-Varela I, Echeverri J, Caralt M, Lázaro JL, Charco R. Analysis of adult 20-year survivors after liver transplantation. Hepatol Int 2014; 9:461-70. [PMID: 25788182 PMCID: PMC4473278 DOI: 10.1007/s12072-014-9577-x] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2014] [Accepted: 08/21/2014] [Indexed: 02/07/2023]
Abstract
Background Liver transplantation (LT) is the treatment of choice for chronic and acute liver failure; however, the status of long-term survivors and allograft function is not well known. Aim To evaluate the clinical outcome and allograft function of survivors 20 years post-LT, cause of death during the same period and risk factors of mortality. Methods A retrospective study was conducted from prospective, longitudinal data collected at a single center of adult LT recipients surviving 20 years. A comparative sub-analysis was made with patients who were not alive 20 years post-transplantation to identify the causes of death and risk factors of mortality. Results Between 1988 and 1994, 132 patients received 151 deceased-donors LT and 28 (21 %) survived more than 20 years. Regarding liver function in this group, medians of AST, ALT and total bilirubin at 20 years post-LT were 33 IU/L (13–135 IU/L), 27 (11–152 IU/L) and 0.6 mg/dL (0.3–1.1 mg/dL). Renal dysfunction was observed in 40 % of patients and median eGFR among 20-year survivors was 64 mL/min/1.73 m2 (6–144 mL/min/1.73 m2). Sixty-one percent of 20-year survivors had arterial hypertension, 43 % dyslipidemia, 25 % de novo tumors and 21 % diabetes mellitus. Infections were the main cause of death during the 1st year post-transplant (32 %) and between the 1st and 5th year post-transplant (25 %). After 5th year from transplant, hepatitis C recurrence (22 %) became the first cause of death. Factors having an impact on long-term patient survival were HCC indication (p = 0.049), pre-transplant renal dysfunction (p = 0.043) and long warm ischemia time (p = 0.016); furthermore, post-transplant factors were diabetes mellitus (p = 0.001) and liver dysfunction (p = 0.05) at 1 year. Conclusion Our results showed the effect of immunosuppression used during decades on long-term outcome in our LT patients in terms of morbidity (arterial hypertension, diabetes mellitus, dyslipidemia and renal dysfunction) and mortality (infections and hepatitis C recurrence).
Collapse
Affiliation(s)
- C Dopazo
- Department of HBP Surgery and Transplants, Hospital Universitario Vall d´Hebron, Universidad Autónoma de Barcelona, Paseo Vall d´Hebron 119-129, 08035, Barcelona, Spain,
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Kuramitsu K, Fukumoto T, Iwasaki T, Tominaga M, Matsumoto I, Ajiki T, Ku Y. Long-term Complications After Liver Transplantation. Transplant Proc 2014; 46:797-803. [DOI: 10.1016/j.transproceed.2013.11.047] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2013] [Accepted: 11/05/2013] [Indexed: 12/11/2022]
|
|
37
|
Gao YJ, Zhang M, Jin B, Meng FP, Ma XM, Liu ZW, Su HB, Zhao JM, Li HW. Clinical-pathological analysis of hepatitis B virus recurrence after liver transplantation in Chinese patients. J Gastroenterol Hepatol 2014; 29:554-60. [PMID: 24117714 DOI: 10.1111/jgh.12404] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/03/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Liver transplantation (LT) for hepatitis B virus (HBV)-related disease can be complicated by HBV recurrence. The aim of this study was to evaluate the risk factors, prophylaxis treatment, and histological characteristics of HBV recurrence after LT when using long-term, low-dose hepatitis B immunoglobulin (HBIG) plus nucleoside analog (lamivudine [LAM] or entecavir [ETV]). METHODS Retrospective data from 253 adult LT patients using long-term, low-dose HBIG plus nucleoside analog after LT, for a mean treatment duration of 1-72 months, were collected from a single center in Beijing, China. Univariate analyses were conducted to determine the association among gender, age, hepatocellular carcinoma, hepatitis B e antigen-positive status, HBV-DNA level and tyrosine-methionine-aspartate-aspartate (YMDD) mutations on HBV recurrence in these patients. RESULTS Overall, the HBV recurrence rate was 6.32% (16/253). There was no significant difference in the survival rate between the HBV recurrence and non-recurrence groups. Risk factors for HBV recurrence were: hepatitis B e antigen positivity, HBV-DNA > 10(5) copies/mL, hepatocellular carcinoma, and YMDD mutation. Sixteen patients receiving LAM had HBV recurrence (16/169; mean treatment duration: 61.8 ± 18.3 months). No HBV recurrence occurred in patients receiving ETV after LT (0/84; mean treatment duration: 57.1 ± 15.9 months). Differences in rate of mortality and HBV recurrence were not significant between the two groups. CONCLUSIONS LT is an effective treatment for HBV-related end-stage liver disease. The combination of ETV and intramuscular HBIG for HBV recurrence prophylaxis after LT was more effective than LAM, especially in Chinese patients with HBV recurrence risk factors.
Collapse
Affiliation(s)
- Yin-Jie Gao
- Medical School of Chinese PLA, Beijing, China; Department of Infectious Diseases, 302 Military Hospital, Beijing, China
| | | | | | | | | | | | | | | | | |
Collapse
|
|
38
|
Li Z, Hu Z, Xiang J, Zhou J, Yan S, Wu J, Zhou L, Zheng S. Use of hepatitis B surface antigen-positive grafts in liver transplantation: a matched analysis of the US National database. Liver Transpl 2014; 20:35-45. [PMID: 24142889 DOI: 10.1002/lt.23774] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2013] [Accepted: 09/30/2013] [Indexed: 12/27/2022]
Abstract
The scarcity of available donor organs is the key challenge in orthotopic liver transplantation (OLT). A viable way of expanding the donor pool is the use of liver grafts from hepatitis B surface antigen (HBsAg)-positive donors. The present study used the US Scientific Registry of Transplant Recipients database (1987-2010), and each of the 78 patients who underwent OLT with HBsAg-positive grafts was matched with 4 patients who received HBsAg-negative grafts by urgent status, donor sex, recipient sex, donor age, recipient age, transplant date, Model for End-Stage Liver Disease score, and warm ischemia time. The overall graft and patient survival rates were similar for recipients of HBsAg-positive grafts and matched controls: the 5-year graft survival rates were 66% and 64%, respectively (P = 0.95), and the 5-year patient survival rates were 71% and 71%, respectively (P = 0.87). A Cox proportional hazards regression analysis that was adjusted for other variables showed no impact of the donor HBsAg status on graft or patient survival. The use of hepatitis B immunoglobulin (HBIG) was independently associated with better posttransplant graft survival [hazard ratio (HR) = 0.23, 95% confidence interval (CI) = 0.06-0.81] and patient survival (HR = 0.16, 95% CI = 0.04-0.75) for recipients of HBsAg-positive grafts. In conclusion, the use of HBsAg-positive liver grafts did not reduce posttransplant graft or patient survival. Moreover, matching these donors to recipients treated with HBIG may improve safety.
Collapse
Affiliation(s)
- Zhiwei Li
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China
| | | | | | | | | | | | | | | |
Collapse
|
|
39
|
Watt KD. Extrahepatic implications of metabolic syndrome. Liver Transpl 2013; 19 Suppl 2:S56-61. [PMID: 23960041 DOI: 10.1002/lt.23726] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2013] [Accepted: 08/08/2013] [Indexed: 02/07/2023]
Affiliation(s)
- Kymberly D Watt
- Division of Gastroenterology and Hepatology, William J. von Liebig Transplant Center, Mayo Clinic and Foundation, Rochester, MN
| |
Collapse
|
|
40
|
Schoening WN, Buescher N, Rademacher S, Andreou A, Kuehn S, Neuhaus R, Guckelberger O, Puhl G, Seehofer D, Neuhaus P. Twenty-year longitudinal follow-up after orthotopic liver transplantation: a single-center experience of 313 consecutive cases. Am J Transplant 2013; 13:2384-94. [PMID: 23915357 DOI: 10.1111/ajt.12384] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2013] [Revised: 05/13/2013] [Accepted: 06/12/2013] [Indexed: 02/06/2023]
Abstract
With excellent short-term survival in liver transplantation (LT), we now focus on long-term outcome and report the first European single-center 20-year survival data. Three hundred thirty-seven LT were performed in 313 patients (09/88-12/92). Impact on long-term outcome was studied and a comparison to life expectancy of matched normal population was performed. A detailed analysis of 20-years follow-up concerning overweight (HBMI), hypertension (HTN), diabetes (HGL), hyperlipidemia (HLIP) and moderately or severely impaired renal function (MIRF, SIRF) is presented. Patient and graft survival at 1, 10, 20 years were 88.4%, 72.7%, 52.5% and 83.7%, 64.7% and 46.6%, respectively. Excluding 1-year mortality, survival in the elderly LT recipients was similar to normal population. Primary indication (p < 0.001), age (p < 0.001), gender (p = 0.017), impaired renal function at 6 months (p < 0.001) and retransplantation (p = 0.034) had significant impact on patient survival. Recurrent disease (21.3%), infection (20.6%) and de novo malignancy (19.9%) were the most common causes of death. Prevalence of HTN (57.3-85.2%, p < 0.001), MIRF (41.8-55.2%, p = 0.01) and HBMI (33.2-45%, p = 0.014) increased throughout follow-up, while prevalence of HLIP (78.0-47.6%, p < 0.001) declined. LT has conquered many barriers to achieve these outstanding long-term results. However, much work is needed to combat recurrent disease and side effects of immunosuppression (IS).
Collapse
|
|
41
|
Kressel A, Therapondos G, Bohorquez H, Borg B, Bruce D, Carmody I, Cohen A, Girgrah N, Joshi S, Reichman T, Loss GE. Excellent liver retransplantation outcomes in hepatitis C-infected recipients. Clin Transplant 2013; 27:E512-20. [DOI: 10.1111/ctr.12182] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/01/2013] [Indexed: 12/15/2022]
Affiliation(s)
- A. Kressel
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
| | - G. Therapondos
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
| | - H. Bohorquez
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
| | - B. Borg
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
| | - D. Bruce
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
| | - I. Carmody
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
| | - A. Cohen
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
| | - N. Girgrah
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
| | - S. Joshi
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
| | - T. Reichman
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
| | - G. E. Loss
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
| |
Collapse
|
|
42
|
Arshad F, Lisman T, Porte RJ. Hypercoagulability as a contributor to thrombotic complications in the liver transplant recipient. Liver Int 2013; 33:820-7. [PMID: 23490221 DOI: 10.1111/liv.12140] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2012] [Accepted: 02/04/2013] [Indexed: 12/13/2022]
Abstract
Traditionally, perioperative bleeding complications were a major concern during orthotopic liver transplantation, but a tremendous decline in transfusion requirements has been reported over the last decade. In recent years, there has been an increasing awareness towards perioperative thrombotic complications, including liver vessel thrombosis, and systemic venous and arterial thromboembolic events. Whereas a number of these thrombotic complications were previously categorized as surgical complications, increasing clinical and laboratory evidence suggest a role for the haemostatic system in thrombotic complications occurring during and after transplantation. High levels of the platelet adhesive protein von Willebrand factor with low levels of its regulator ADAMTS13, an increased potential to generate thrombin, and temporary hypofibrinolysis are all indicative of increased haemostatic potential after transplantation. Clinical evidence for a role of the haemostatic system in post-operative thromboses includes a higher thrombotic risk in patients with various acquired thrombotic risk factors. Although data on efficacy of anticoagulant therapy after liver transplantation are scarce, one study has shown a significant decrease in the risk for late hepatic artery thrombosis by antithrombotic therapy with aspirin. These findings suggest that antihaemostatic therapy in prevention or treatment of thromboembolic complications after liver transplantation may be relevant. Studies on efficacy and safety of these interventions are required as many of the thrombotic complications have a pronounced negative impact on graft and patient survival.
Collapse
Affiliation(s)
- Freeha Arshad
- Section Hepatobiliairy Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | | | | |
Collapse
|
|
43
|
Rubín A, Sánchez-Montes C, Aguilera V, Juan FS, Ferrer I, Moya A, Montalva E, Pareja E, López-Andujar R, Prieto M, Berenguer M. Long-term outcome of 'long-term liver transplant survivors'. Transpl Int 2013; 26:740-50. [PMID: 23714220 DOI: 10.1111/tri.12118] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2012] [Revised: 07/18/2012] [Accepted: 04/20/2013] [Indexed: 12/13/2022]
Abstract
There are few studies focusing on long-term complications in liver transplant (LT) recipients. The aim of this study was to define the outcome of LT recipients having survived at least 10 years from LT. Of 323 adult LT done between 1991 and 1997, the 167(52%) alive >10 years post-LT (baseline time) formed the study population. Long-term outcome measures included the following: immunosuppression, metabolic complications [obesity, arterial hypertension (AH), diabetes, dislypidemia], cardiovascular events (CVE), chronic renal dysfunction-CRD, and de novo tumors. Median age at LT was 50 years. Most common indication was postnecrotic cirrhosis (89%), mostly because of HCV (46%). At study-baseline (10 years post-LT), 29% were obese and AH, diabetes, dislypidemia, and CRD were present in 75%, 30%, 42%, and 36%, respectively. In most cases, these complications were already present 1 year post-LT; less than one quarter developed them onward. The 6 year cumulative survival since baseline reached 84% (n = 24 deaths), with most deaths related to recurrent graft diseases (mostly HCV) followed by de novo tumors or CVE. 1, 3, 5 and 10 years cumulative rates of CVE and de novo tumors since baseline were 2%, 5%, 10% and 17%, and 1%, 3%, 6% and 13%, respectively. Chronic renal impairment was independently associated with survival and development of CVE since baseline. The medium-term survival of 'long-term survivors', i.e. patients alive 10 years after LT is good, but metabolic complications and CRD are common and continue to increase afterwards. Cardiovascular events and de novo tumors increase gradually over time and represent a major cause of late mortality.
Collapse
Affiliation(s)
- Angel Rubín
- Liver Transplantation and Hepatology Unit, La Fe Hospital, Valencia, Spain
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
44
|
Mu JZ, Chen QY, Sun CY, Wu YH, Zhu L. Current status of research on enterogenic infection following liver transplantation. Shijie Huaren Xiaohua Zazhi 2013; 21:1055-1061. [DOI: 10.11569/wcjd.v21.i12.1055] [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] [Indexed: 02/06/2023] Open
Abstract
Since the introduction of the Milan criteria in 1996, liver transplantation has become a standard therapy for end-stage liver diseases and hepatocellular carcinoma. In recent years, liver transplantation has developed greatly. Survival rates after liver transplantation have markedly improved as a result of improved operative techniques, use of immunosuppressants, etc. But infection, especially enterogenic infection, is still the most disturbing complication in patients undergoing liver transplantation. This article gives an overview of infection after liver transplantation and focuses on the discussion of enterogenic infection in terms of its pathophysiology, risk factors, outcome, diagnosis and treatment.
Collapse
|
|
45
|
Burra P, De Martin E, Gitto S, Villa E. Influence of age and gender before and after liver transplantation. Liver Transpl 2013; 19:122-34. [PMID: 23172830 DOI: 10.1002/lt.23574] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2012] [Accepted: 11/08/2012] [Indexed: 12/15/2022]
Abstract
Women constitute a particular group among patients with chronic liver disease and in the post-liver transplantation (LT) setting: they are set apart not only by traditional differences with respect to men (ie, body mass index, different etiologies of liver disease, and accessibility to transplantation) but also in increasingly evident ways related to hormonal changes that characterize first the fertile age and subsequently the postmenopausal period (eg, disease course variability and responses to therapy). The aim of this review is, therefore, to evaluate the role of the interplay of factors such as age, gender, and hormones in influencing the natural history of chronic liver disease before and after LT and their importance in determining outcomes after LT. As the population requiring LT ages and the mean age at transplantation increases, older females are being considered for transplantation. Older patients are at greater risk for nonalcoholic steatohepatitis, osteoporosis, and a worse response to antiviral therapy. Female gender per se is associated with a greater risk for osteoporosis because of metabolic changes after menopause, the bodily structure of females, and, in the population of patients with chronic liver disease, the greater prevalence of cholestatic and autoimmune liver diseases. With menopause, the fall of protective estrogen levels can lead to increased fibrosis progression, and this represents a negative turning point for women with chronic liver disease and especially for patients with hepatitis C. Therefore, the notion of gender as a binary female/male factor is now giving way to the awareness of more complex disease processes within the female gender that follow hormonal, social, and age patterns and need to be addressed directly and specifically.
Collapse
Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Padua, Italy.
| | | | | | | |
Collapse
|
|
46
|
Marschalek J, Györi GP, Silberhumer GR, Jomrich G, Kristo I, Steininger R, Mühlbacher F, Berlakovich GA. Simultaneous pancreas-kidney transplantation nine years after liver transplantation--a case report. Transplant Proc 2012. [PMID: 23195023 DOI: 10.1016/j.transproceed.2012.06.068] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
In this case report we have described a patient suffering from sclerosing cholangitis, diabetes mellitus type I, and consequent end-stage renal disease who was successfully treated with simultaneous pancreas and kidney transplantation 9 years after orthotopic liver transplantation.
Collapse
Affiliation(s)
- J Marschalek
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria
| | | | | | | | | | | | | | | |
Collapse
|
|
47
|
Abstract
Metabolic syndrome (MS) is a cluster of metabolic derangements associated with insulin resistance and an increased risk of cardiovascular mortality. MS has become a major health concern worldwide and is considered to be the etiology of the current epidemic of diabetes and cardiovascular disease. In addition to cardiovascular disease, the presence of MS is also closely associated with other comorbidities including nonalcoholic fatty liver disease (NAFLD). The prevalence of MS in patients with cirrhosis and end-stage liver disease is not well established and difficult to ascertain. Following liver transplant, the prevalence of MS is estimated to be 44-58%. The main factors associated with posttransplant MS are posttransplant diabetes, obesity, dyslipidemia, and hypertension. In addition to developing NAFLD, posttransplant MS is associated with increased cardiovascular mortality that is 2.5 times that of the age- and sex-matched individuals. Additionally, the presence of posttransplant MS has been associated with rapid progression to fibrosis in individuals transplanted for HCV cirrhosis. There is an urgent need for well-designed prospective studies to fully delineate the natural history and risk factors associated with posttransplant MS. Until then, early recognition, prevention, and treatment of its components are vital in improving outcomes in liver transplant recipients.
Collapse
|
|
48
|
Long-term outcomes of calcineurin inhibitor withdrawal for post-liver transplant renal dysfunction. Transplant Proc 2011; 43:3802-6. [PMID: 22172850 DOI: 10.1016/j.transproceed.2011.10.044] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2011] [Accepted: 10/12/2011] [Indexed: 11/23/2022]
Abstract
BACKGROUND It has become common practice to withdraw or reduce calcineurin inhibitors (CNI) in patients with renal dysfunction after liver transplantation; however, little is known about the long-term outcome of this strategy. This study investigates the long-term results of CNI withdrawal for post-liver transplant renal dysfunction and examines for factors that predict a significant improvement in renal function. METHODS A retrospective database review was performed to examine outcomes in patients with CNI withdrawn for chronic renal impairment. Univariate analyses were used to identify predictors of an improvement in creatinine clearance (CrC). RESULTS Sixty patients (44 males) were included. Of these, 82% of patients were switched to mycophenolate mofetil and 18% azathioprine. Median follow-up after CNI withdrawal was 48 (range 3-72) months. Postwithdrawal, there was an initial improvement in CrCl (mean 5.5 mL), which remained above baseline levels at 6 years. Acute cellular rejection developed in six patients (10%), but there was no rejection-associated graft loss. A shorter time from transplantation to conversion was associated with greatest improvement in CrCI. CONCLUSIONS CNI withdrawal is associated with a significant initial improvement and then arrest in long-term decline of renal function. Rejection in this setting is uncommon. The greatest benefit is seen in patients switched within the early years after transplantation.
Collapse
|
|
49
|
Prothrombotic Gene Polymorphisms: Possible Contributors to Hepatic Artery Thrombosis After Orthotopic Liver Transplantation. Transplantation 2011; 92:587-93. [DOI: 10.1097/tp.0b013e318228063b] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
|
|
50
|
Abstract
BACKGROUND Late survival is not improving after liver transplantation. In this study, possible reasons for this were investigated. METHODS Mortality rates and causes of death were ascertained in 4483 adult primary liver allograft recipients surviving 1 year or more from engraftment, identified through the UK Transplant Database and transplanted between 1994 and 2007. Associations with death, cause of death, and retransplantation were assessed. RESULTS Mortality in those surviving beyond 1 year in UK liver transplant recipients was more than twice that expected in the general population and had not improved during the study period, independent of cause of liver disease, recipient age, recipient gender, and donor age. The major causes of death were malignancy (30.6%), multisystem failure (10.0%), infection (9.8%), cardiac disease (8.7%), and graft failure (9.8%). Associations with death after 1 year were pretransplant etiologies alcohol-related liver disease (hazard ratio [HR]=2.10), autoimmune hepatitis or cryptogenic (HR=1.68), hepatitis C virus (HR=2.51), and hepatocellular carcinoma (HR=4.19). Associations with retransplantation were recipient age (HR=0.95 per year), donor age (HR=1.02 per year), and hepatitis C virus (HR=2.04). Hepatocellular carcinoma and recipient age were associated with cancer-related death (odds ratio=1.87 and 1.02 per year). Recipient age was associated with cardiac death (odds ratio=1.06 per year). CONCLUSIONS Strategies to reduce late mortality after liver transplantation are required. These may include prevention of disease recurrence, improved recipient selection, and addressing risk factors for death in late survivors of liver transplantation.
Collapse
|