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Zhou J, Zhang S, Liu J, Ding J, Ren S, Zhang T, Ye D, Xu F, Chen Z, Zheng H, Zhang L, Zhang Y, Hu Z. The Association of Age and Liver Transplant Outcomes in Patients With Acute-On-Chronic Liver Failure. J Surg Res 2025; 309:199-211. [PMID: 40267818 DOI: 10.1016/j.jss.2025.03.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 02/20/2025] [Accepted: 03/17/2025] [Indexed: 04/25/2025]
Abstract
INTRODUCTION To explore the role of age at listing on outcomes for patients with acute-on-chronic liver failure (ACLF) awaiting liver transplantation (LT). MATERIALS AND METHODS We assessed adult candidates listed for LT in the Scientific Registry of Transplant Recipients database from January 1, 2007 to June 30, 2018. Patients were divided into four groups based on age at listing: I (≤34), II (35-49), III (50-64), and IV (≥65). The ACLF grade was estimated (est-ACLF), and intent-to-treat survival, overall survival (OS), as well as potential predictors for OS was evaluated. RESULTS Est-ACLF-3 was associated with a higher 30-d cumulative dropout rate and inferior intent-to-treat survival across age groups. No difference was observed in OS among ACLF grades in group I, but significantly inferior OS was observed in higher ACLF grades in groups II-IV. Multivariate analysis showed age (P < 0.001, ref. group I; hazard ratio 0.995 for group II, P = 0.936; 1.196 for group III, P = 0.002; 1.651 for group IV, P < 0.001) and est-ACLF grade (P < 0.001, ref. est-ACLF-0; 1.214 for est-ACLF-1, P < 0.001; 1.246 for est-ACLF-2, P < 0.001; 1.578 for est-ACLF-3, P < 0.001) were independent predictors for OS. Generalized additive model showed different association between age and OS among different ACLF grades. CONCLUSIONS Young patients with high ACLF grades could achieve similar OS compared with those with low grades. Elderly patients with higher ACLF grades were associated with inferior outcomes after LT.
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Affiliation(s)
- Jie Zhou
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Siyao Zhang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, Zhejiang, China
| | - Jingxia Liu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Jiawei Ding
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, Zhejiang, China
| | - Shenli Ren
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, Zhejiang, China
| | - Tao Zhang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, Zhejiang, China
| | - Danni Ye
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, Zhejiang, China
| | - Fangshen Xu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, Zhejiang, China
| | - Zheng Chen
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, Zhejiang, China
| | - Huilin Zheng
- Zhejiang Provincial Collaborative Innovation Center of Agricultural Biological Resource Biochemical Manufacturing, School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou, Zhejiang, China
| | - Lei Zhang
- Zhejiang Provincial Collaborative Innovation Center of Agricultural Biological Resource Biochemical Manufacturing, School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou, Zhejiang, China
| | - Yu Zhang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Zhenhua Hu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, Zhejiang, China.
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Skladaný Ĺ, Žilinčanová D, Žilinčan M, Okapec S, Danček F, Adamcová-Selčanová S, Kukla M, Koller T. Hepatic venous pressure gradient in patients with (compensated and decompensated) advanced chronic liver disease - A comparison of metabolic dysfunction-associated steatotic liver disease with alcohol-associated liver disease: A retrospective view. PLoS One 2025; 20:e0317287. [PMID: 40043074 PMCID: PMC11882044 DOI: 10.1371/journal.pone.0317287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Accepted: 12/25/2024] [Indexed: 05/03/2025] Open
Abstract
BACKGROUND AND AIMS Hepatic venous pressure gradient (HVPG) is a strong surrogate of severity and outcome but its relative prognostic value in metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD) is yet to be clarified. We compared HVPG in MASLD with ALD and other etiologies according to cirrhosis complications. PATIENTS AND METHODS In our cirrhosis registry RH7, we identified patients with data on HVPG and scrutinized them against the etiology of advanced chronic liver disease (ACLD) (MASLD, ALD, Other) and specific complications of ACLD such as variceal bleeding or ascites. We excluded patients with advanced malignancies and less than 6 months of follow-up. RESULTS We enrolled 220 patients with ALD, MASLD, and Other etiology in 128, 52, and 40 cases, respectively; te median age was 57, 60, and 52 years (P = 0.09); the proportion of females was 31, 67, and 55%, respectively (P < 0.01). Median MELD scores in ALD, MASLD, and Other etiologies were 16.0, 13.0, and 12.0 (P < 0.01), and the median HVPG was 18.0, 14.0, and 11.5 mmHg (P < 0.001). In 19, 30, and 25 compensated patients, the median HVPG was 10.0, 11.5, and 11.0 mmHg (P = 0.97). In 109, 22, and 15 decompensated patients, the median HVPG was 19.0, 15.5 and 14 mmHg (P = 0.01 for trend, difference ALD vs. other P < 0.01, ALD vs. MASLD, P = 0.295). Between decompensated MASLD and ALD patients, we observed no differences in the proportion of clinically significant portal hypertension (CSPH) (>10 mmHg). CONCLUSION In our cirrhosis registry study of hospitalized patients with ACLD, baseline HVPG measured for accepted indications differed according to the etiology of dACLD: patients with ALD had the highest values followed by MASLD and Other etiologies. Importantly, when looked at from the point of view of complications, the treshold for clinically significant portal hypertension remained fixed at the level recommended by BAVENO Consensus - 10 mm Hg irrespective of etiology.
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Affiliation(s)
- Ĺubomír Skladaný
- Department of Hepatology, Gastroenterology, and Transplantation, 2nd Department of Medicine, Slovak Medical University Faculty of Medicine, F. D. Roosevelt Hospital, Banska Bystrica, Slovakia
| | - Daniela Žilinčanová
- Department of Hepatology, Gastroenterology, and Transplantation, 2nd Department of Medicine, Slovak Medical University Faculty of Medicine, F. D. Roosevelt Hospital, Banska Bystrica, Slovakia
| | - Michal Žilinčan
- Department of Radiology, FD Roosevelt Hospital, Banská Bystrica, Slovakia
| | - Stanislav Okapec
- Department of Radiology, FD Roosevelt Hospital, Banská Bystrica, Slovakia
| | - Filip Danček
- Department of Radiology, FD Roosevelt Hospital, Banská Bystrica, Slovakia
| | - Svetlana Adamcová-Selčanová
- Department of Hepatology, Gastroenterology, and Transplantation, 2nd Department of Medicine, Slovak Medical University Faculty of Medicine, F. D. Roosevelt Hospital, Banska Bystrica, Slovakia
| | - Michal Kukla
- Department of Internal Medicine and Geriatrics, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland
- Department of Endoscopy, University Hospital in Kraków, Kraków, Poland
| | - Tomáš Koller
- Subdivision of Gastroenterology and Hepatology, 5th Department of Medicine, Comenius University Faculty of Medicine, University Hospital Bratislava, Bratislava, Slovakia
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Seth R, Andreoni KA. Changing landscape of liver transplant in the United States- time for a new innovative way to define and utilize the "non-standard liver allograft"-a proposal. FRONTIERS IN TRANSPLANTATION 2024; 3:1449407. [PMID: 39176402 PMCID: PMC11338891 DOI: 10.3389/frtra.2024.1449407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Accepted: 07/22/2024] [Indexed: 08/24/2024]
Abstract
Since the first liver transplant was performed over six decades ago, the landscape of liver transplantation in the US has seen dramatic evolution. Numerous advancements in perioperative and operative techniques have resulted in major improvements in graft and patient survival rates. Despite the increase in transplants performed over the years, the waitlist mortality rate continues to remain high. The obesity epidemic and the resultant metabolic sequelae continue to result in more marginal donors and challenging recipients. In this review, we aim to highlight the changing characteristics of liver transplant recipients and liver allograft donors. We focus on issues relevant in successfully transplanting a high model for end stage liver disease recipient. We provide insights into the current use of terms and definitions utilized to discuss marginal allografts, discuss the need to look into more consistent ways to describe these organs and propose two new concepts we coin as "Liver Allograft Variables" (LAV) and "Liver Allograft Composite Score" (LACS) for this. We discuss the development of spectrum of risk indexes as a dynamic tool to characterize an allograft in real time. We believe that this concept has the potential to optimize the way we allocate, utilize and transplant livers across the US.
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Affiliation(s)
- Rashmi Seth
- Department of Surgery, Division of Transplant Surgery, University of Tennessee Health Sciences Center, Methodist University Hospital Transplant Institute, Memphis, TN, United States
| | - Kenneth A. Andreoni
- Department of Surgery, Division of Abdominal Transplantation, Thomas Jefferson University, Philadelphia, PA, United States
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Robinson T, Vargas PA, Oberholzer J, Pelletier S, Goldaracena N. Survival after LDLT in recipients ≥70 years old in the United States. An OPTN/UNOS liver transplant registry analysis. Clin Transplant 2023; 37:e15099. [PMID: 37589889 DOI: 10.1111/ctr.15099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 07/24/2023] [Accepted: 08/07/2023] [Indexed: 08/18/2023]
Abstract
BACKGROUND Living donor liver transplantation (LDLT) in the elderly population is currently not well studied. There are single-center studies indicating that patient age should not be a barrier to LDLT, with similar outcomes compared to younger recipients. METHODS Using UNOS/STAR data from 2010 to 2022 we retrospectively analyzed patients ≥70 years old receiving a living donor graft (LDLT ≥70y group) versus a deceased donor graft (DDLT ≥70y group). In addition, we compared recipients ≥70 years old undergoing LDLT versus patients 18-69 years old also undergoing LDLT. Donor and recipient baseline characteristics, as well as postoperative outcomes including graft and patient survival were analyzed and compared between groups. RESULTS Recipients in the LDLT ≥70y group showed less disease burden and spent significantly less time on the waitlist when compared to recipients in the DDLT ≥70y group (102 [49-201] days versus 170 [36-336] days) respectively; p = .004. With the exception of a longer length of stay (LOS) in the LDLT ≥70y group (p ≤ .001), postoperative outcomes were comparable with recipients in the DDLT ≥70y group, including similar graft and patient survival rates at 1-, 3-, and 5-years. When compared to younger recipients of a graft from a living donor, patients in the LDLT ≥70y group had similar post-transplant functional status, re-transplant rates and similar causes contributing to graft failure. However, significantly lower graft and patient survival rates were observed. CONCLUSION LDLT for recipients aged 70 or greater represents a faster access to transplantation in a safe and feasible manner when compared to similar- aged recipients undergoing DDLT.
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Affiliation(s)
- Todd Robinson
- Division of Transplant Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, Virginia, USA
| | - Paola A Vargas
- Division of Transplant Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, Virginia, USA
| | - Jose Oberholzer
- Division of Transplant Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, Virginia, USA
| | - Shawn Pelletier
- Division of Transplant Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, Virginia, USA
| | - Nicolas Goldaracena
- Division of Transplant Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, Virginia, USA
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Famularo S, Cillo U, Lauterio A, Donadon M, Vitale A, Serenari M, Cipriani F, Fazio F, Giuffrida M, Ardito F, Dominioni T, Garancini M, Lai Q, Nicolini D, Molfino S, Perri P, Pinotti E, Conci S, Ferrari C, Zanello M, Patauner S, Zimmitti G, Germani P, Chiarelli M, Romano M, De Angelis M, La Barba G, Troci A, Ferraro V, Izzo F, Antonucci A, Belli A, Memeo R, Crespi M, Ercolani G, Boccia L, Zanus G, Tarchi P, Hilal MA, Frena A, Jovine E, Griseri G, Ruzzenente A, Zago M, Grazi G, Baiocchi GL, Vivarelli M, Rossi M, Romano F, Maestri M, Giuliante F, Valle RD, Ferrero A, Aldrighetti L, De Carlis L, Cescon M, Torzilli G. Survival benefit of second line therapies for recurrent hepatocellular carcinoma: repeated hepatectomy, thermoablation and second-line transplant referral in a real life national scenario. HPB (Oxford) 2023; 25:1223-1234. [PMID: 37357112 DOI: 10.1016/j.hpb.2023.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 05/05/2023] [Accepted: 06/10/2023] [Indexed: 06/27/2023]
Abstract
BACKGROUND Despite second-line transplant(SLT) for recurrent hepatocellular carcinoma(rHCC) leads to the longest survival after recurrence(SAR), its real applicability has never been reported. The aim was to compare the SAR of SLT versus repeated hepatectomy and thermoablation(CUR group). METHODS Patients were enrolled from the Italian register HE.RC.O.LE.S. between 2008 and 2021. Two groups were created: CUR versus SLT. A propensity score matching (PSM) was run to balance the groups. RESULTS 743 patients were enrolled, CUR = 611 and SLT = 132. Median age at recurrence was 71(IQR 6575) years old and 60(IQR 53-64, p < 0.001) for CUR and SLT respectively. After PSM, median SAR for CUR was 43 months(95%CI = 37 - 93) and not reached for SLT(p < 0.001). SLT patients gained a survival benefit of 9.4 months if compared with CUR. MilanCriteria(MC)-In patients were 82.7% of the CUR group. SLT(HR 0.386, 95%CI = 0.23 - 0.63, p < 0.001) and the MELD score(HR 1.169, 95%CI = 1.07 - 1.27, p < 0.001) were the only predictors of mortality. In case of MC-Out, the only predictor of mortality was the number of nodules at recurrence(HR 1.45, 95%CI= 1.09 - 1.93, p = 0.011). CONCLUSION It emerged an important transplant under referral in favour of repeated hepatectomy or thermoablation. In patients with MC-Out relapse, the benefit of SLT over CUR was not observed.
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Affiliation(s)
- Simone Famularo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; Surgical Data Science Team, Research Institute Against Digestive Cancer (IRCAD), Strasbourg, France.
| | - Umberto Cillo
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova, Second General Surgical Unit, Padova Teaching Hospital, Padua, Italy
| | - Andrea Lauterio
- Department of General and Transplant Surgery, Grande Ospedale Metropolitano Niguarda, School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | - Matteo Donadon
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Alessandro Vitale
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova, Second General Surgical Unit, Padova Teaching Hospital, Padua, Italy
| | - Matteo Serenari
- Hepato-biliary Surgery and Transplant Unit, Policlinico Sant'Orsola IRCCS, Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Federica Cipriani
- Hepatobiliary Surgery Division, "Vita e Salute" University, Ospedale San Raffaele IRCCS, Milano, Italy
| | - Federico Fazio
- Department of General and Oncological Surgery, Mauriziano Hospital "Umberto I", Turin, Italy
| | - Mario Giuffrida
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Francesco Ardito
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Catholic University of the Sacred Heart, Rome, Italy
| | - Tommaso Dominioni
- Unit of General Surgery 1, University of Pavia and Foundation IRCCS Policlinico San Matteo, Pavia, Italy
| | - Mattia Garancini
- School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Umberto I Polyclinic of Rome, Rome, Italy
| | - Daniele Nicolini
- HPB Surgery and Transplantation Unit, Department of Clinical and Experimental Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Sarah Molfino
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Pasquale Perri
- Division of Hepatobiliarypancreatic Unit, IRCCS - Regina Elena National Cancer Institute, Rome, Italy
| | - Enrico Pinotti
- Department of Surgery, Ponte San Pietro Hospital, Bergamo, Italy
| | - Simone Conci
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
| | | | - Matteo Zanello
- Alma Mater Studiorum, University of Bologna, AOU Sant'Orsola Malpighi, IRCCS at Maggiore Hospital, Bologna, Italy
| | - Stefan Patauner
- Department of General and Pediatric Surgery, Bolzano Central Hospital, Bolzano, Italy
| | - Giuseppe Zimmitti
- Department of General Surgery, Poliambulanza Foundation Hospital, Brescia, Italy
| | - Paola Germani
- Division of General Surgery, Department of Medical and Surgical Sciences, ASUGI, Trieste, Italy
| | - Marco Chiarelli
- Department of Emergency and Robotic Surgery, ASST Lecco, Lecco, Italy
| | - Maurizio Romano
- Department of Surgical, Oncological and Gastroenterological Science (DISCOG), University of Padua, Hepatobiliary and Pancreatic Surgery Unit - Treviso Hospital, Italy
| | | | - Giuliano La Barba
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Department of Medical and Surgical Sciences - University of Bologna Forlì, Italy
| | - Albert Troci
- Department of Surgery, L. Sacco Hospital, Milan, Italy
| | - Valentina Ferraro
- Department of Hepato-Pancreatic-Biliary Surgery, Miulli Hospital, Bari, Italy
| | - Francesco Izzo
- Division of Epatobiliary Surgical Oncology, Istituto Nazionale Tumori IRCCS Fondazione Pascale-IRCCS di Napoli, Naples, Italy
| | | | - Andrea Belli
- Division of Epatobiliary Surgical Oncology, Istituto Nazionale Tumori IRCCS Fondazione Pascale-IRCCS di Napoli, Naples, Italy
| | - Riccardo Memeo
- Department of Hepato-Pancreatic-Biliary Surgery, Miulli Hospital, Bari, Italy
| | | | - Giorgio Ercolani
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Department of Medical and Surgical Sciences - University of Bologna Forlì, Italy
| | - Luigi Boccia
- Department of General Surgery, Ospedale Carlo Poma, Mantua, Italy
| | - Giacomo Zanus
- Department of Surgical, Oncological and Gastroenterological Science (DISCOG), University of Padua, Hepatobiliary and Pancreatic Surgery Unit - Treviso Hospital, Italy
| | - Paola Tarchi
- Division of General Surgery, Department of Medical and Surgical Sciences, ASUGI, Trieste, Italy
| | - Moh'd Abu Hilal
- Department of General Surgery, Poliambulanza Foundation Hospital, Brescia, Italy
| | - Antonio Frena
- Department of General and Pediatric Surgery, Bolzano Central Hospital, Bolzano, Italy
| | - Elio Jovine
- Alma Mater Studiorum, University of Bologna, AOU Sant'Orsola Malpighi, IRCCS at Maggiore Hospital, Bologna, Italy
| | - Guido Griseri
- HPB Surgical Unit, San Paolo Hospital, Savona, Italy
| | - Andrea Ruzzenente
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
| | - Mauro Zago
- Department of Surgery, Ponte San Pietro Hospital, Bergamo, Italy; Department of Emergency and Robotic Surgery, ASST Lecco, Lecco, Italy
| | - Gianluca Grazi
- Division of Hepatobiliarypancreatic Unit, IRCCS - Regina Elena National Cancer Institute, Rome, Italy
| | - Gian L Baiocchi
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Marco Vivarelli
- HPB Surgery and Transplantation Unit, Department of Clinical and Experimental Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Massimo Rossi
- General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Umberto I Polyclinic of Rome, Rome, Italy
| | - Fabrizio Romano
- School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy
| | - Marcello Maestri
- Unit of General Surgery 1, University of Pavia and Foundation IRCCS Policlinico San Matteo, Pavia, Italy
| | - Felice Giuliante
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Catholic University of the Sacred Heart, Rome, Italy
| | - Raffaele D Valle
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Alessandro Ferrero
- Department of General and Oncological Surgery, Mauriziano Hospital "Umberto I", Turin, Italy
| | - Luca Aldrighetti
- Hepatobiliary Surgery Division, "Vita e Salute" University, Ospedale San Raffaele IRCCS, Milano, Italy
| | - Luciano De Carlis
- Department of General and Transplant Surgery, Grande Ospedale Metropolitano Niguarda, School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | - Matteo Cescon
- Hepato-biliary Surgery and Transplant Unit, Policlinico Sant'Orsola IRCCS, Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Guido Torzilli
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
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Arisar FAQ, Chen S, Chen C, Shaikh N, Karnam RS, Xu W, Asrani SK, Galvin Z, Hirschfield G, Patel K, Tsien C, Selzner N, Cattral M, Lilly L, Bhat M. Availability of living donor optimizes timing of liver transplant in high-risk waitlisted cirrhosis patients. Aging (Albany NY) 2023; 15:8594-8612. [PMID: 37665673 PMCID: PMC10522397 DOI: 10.18632/aging.204982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Accepted: 07/17/2023] [Indexed: 09/06/2023]
Abstract
Liver transplant (LT) candidates have become older and frailer, with growing Non-alcoholic steatohepatitis (NASH) and comorbid disease burden in recent years, predisposing them for poor waitlist outcomes. We aimed to evaluate the impact of access to living donor liver transplantation (LDLT) in waitlisted patients at highest risk of dropout. We reviewed all adult patients with decompensated cirrhosis listed for LT from November 2012 to December 2018. Patients with a potential living donor (pLD) available were identified. Survival analyses with Cox Proportional Hazards models and time to LT with Competing risk models were performed followed by prediction model development. Out of 860 patients who met inclusion criteria, 360 (41.8%) had a pLD identified and 496 (57.6%) underwent LT, out of which 170 (34.2%) were LDLT. The benefit of pLD was evident for all, but patients with moderate to severe frailty at listing (interaction p = 0.03), height <160 cm (interaction p = 0.03), and Model for end stage liver disease (MELD)-Na score <20 (interaction p < 0.0001) especially benefited. Our prediction model identified patients at highest risk of dropout while waiting for deceased donor and most benefiting of pLD (time-dependent area under the receiver operating characteristic curve 0.82). Access to LDLT in a transplant program can optimize the timing of transplant for the increasingly older, frail patient population with comorbidities who are at highest risk of dropout.
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Affiliation(s)
- Fakhar Ali Qazi Arisar
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario M5G 2N2, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario M5G 2N2, Canada
- National Institute of Liver and GI Diseases, Dow University of Health Sciences, Karachi, Sindh 75330, Pakistan
| | - Shiyi Chen
- Department of Biostatistics, Princess Margaret Cancer Center, University Health Network, Toronto, Ontario M5G 2C1, Canada
| | - Catherine Chen
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario M5G 2N2, Canada
| | - Noorulsaba Shaikh
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario M5G 2N2, Canada
| | - Ravikiran Sindhuvalada Karnam
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario M5G 2N2, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario M5G 2N2, Canada
| | - Wei Xu
- Department of Biostatistics, Princess Margaret Cancer Center, University Health Network, Toronto, Ontario M5G 2C1, Canada
- Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario M5G 2C1, Canada
| | - Sumeet K. Asrani
- Division of Hepatology, Department of Medicine, Baylor University Medical Center, Dallas, TX 75246, USA
| | - Zita Galvin
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario M5G 2N2, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario M5G 2N2, Canada
| | - Gideon Hirschfield
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario M5G 2N2, Canada
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario M5G 2C4, Canada
| | - Keyur Patel
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario M5G 2N2, Canada
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario M5G 2C4, Canada
| | - Cynthia Tsien
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario M5G 2N2, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario M5G 2N2, Canada
| | - Nazia Selzner
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario M5G 2N2, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario M5G 2N2, Canada
| | - Mark Cattral
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario M5G 2N2, Canada
- Department of Surgery, University of Toronto, Toronto, Ontario M5G 2N2, Canada
| | - Leslie Lilly
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario M5G 2N2, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario M5G 2N2, Canada
| | - Mamatha Bhat
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario M5G 2N2, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario M5G 2N2, Canada
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7
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Vogliotti E, Ceolin C, Valenti M, Vanin J, Campodall'Orto C, Tonon M, Zanforlini BM, Curreri C, Devita M, De Rui M, Coin A, Cillo U, Burra P, Angeli P, Sergi G. Can the Multidimensional Prognostic Index (MPI) be a predictive instrument for mortality in older adult liver transplant candidates? Eur Geriatr Med 2023; 14:851-859. [PMID: 37460836 PMCID: PMC10447597 DOI: 10.1007/s41999-023-00826-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Accepted: 06/19/2023] [Indexed: 08/25/2023]
Abstract
PURPOSE The most recent guidelines recommend that selection of liver transplant recipient patients be guided by a multidimensional approach that includes frailty assessment. Different scales have been developed to identify frail patients and determine their prognosis, but the data on older adult candidates are still inconclusive. The aim of this study was to compare the accuracy of the Liver Frailty Index (LFI) and the Multidimensional Prognostic Index (MPI) as predictors of mortality in a cohort of older people patients being evaluated for liver transplantation. METHODS This retrospective study was conducted on 68 patients > 70 years being followed at the University Hospital of Padua in 2018. Clinical information on each patient, Model For End-Stage Liver Disease (MELD), Body Mass Index (BMI), Activities of Daily Living (ADL), Mini Nutritional Assessment (MNA), LFI, MPI, and date-of-death, were recorded. The observational period was 3 years. RESULTS We studied 68 individuals (25 women), with a mean age 72.21 ± 1.64 years. Twenty-five (36.2%) patients died during the observational period. ROC curve analysis showed both MPI and LFI to be good predictors of mortality (AUC 0.7, p = 0.007, and AUC 0.689, p = 0.015, respectively). MELD (HR 1.99, p = 0.001), BMI (HR 2.34, p = 0.001), and poor ADL (HR 3.34, p = 0.04) were risk factors for mortality in these patients, while male sex (HR 0.1, p = 0.01) and high MNA scores (HR 0.57, p = 0.01) were protective factors. CONCLUSION Our study confirmed the prognostic value of MPI in older adult patients awaiting liver transplantation. In this cohort, good nutritional status and male sex were protective factors, while high MELD and BMI scores and poor functional status were risk factors.
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Affiliation(s)
- Edoardo Vogliotti
- Division of Geriatrics, Department of Medicine, University of Padua, Via Giustiniani 2, 35128, Padua, Italy
| | - Chiara Ceolin
- Division of Geriatrics, Department of Medicine, University of Padua, Via Giustiniani 2, 35128, Padua, Italy.
| | - Matteo Valenti
- Division of Geriatrics, Department of Medicine, University of Padua, Via Giustiniani 2, 35128, Padua, Italy
| | - Jessica Vanin
- Division of Geriatrics, Department of Medicine, University of Padua, Via Giustiniani 2, 35128, Padua, Italy
| | - Carlotta Campodall'Orto
- Division of Geriatrics, Department of Medicine, University of Padua, Via Giustiniani 2, 35128, Padua, Italy
| | - Marta Tonon
- Internal Medicine and Hepatology Unit, Department of Medicine, University of Padua, Padua, Italy
| | | | - Chiara Curreri
- Division of Geriatrics, University Hospital of Padua, Padua, Italy
| | - Maria Devita
- Department of General Psychology (DPG), University of Padua, Padua, Italy
- Division of Geriatrics, Department of Medicine, University of Padua, Via Giustiniani 2, 35128, Padua, Italy
| | - Marina De Rui
- Division of Geriatrics, University Hospital of Padua, Padua, Italy
| | - Alessandra Coin
- Division of Geriatrics, Department of Medicine, University of Padua, Via Giustiniani 2, 35128, Padua, Italy
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy
| | - Paolo Angeli
- Internal Medicine and Hepatology Unit, Department of Medicine, University of Padua, Padua, Italy
| | - Giuseppe Sergi
- Division of Geriatrics, Department of Medicine, University of Padua, Via Giustiniani 2, 35128, Padua, Italy
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8
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Melandro F, Lai Q, Ghinolfi D, Manzia TM, Spoletini G, Rossi M, Agnes S, Tisone G, De Simone P. Outcome of liver transplantation in elderly patients: an Italian multicenter case-control study. Updates Surg 2023; 75:541-552. [PMID: 36814042 DOI: 10.1007/s13304-023-01448-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 02/03/2023] [Indexed: 02/24/2023]
Abstract
Despite the controversial results of liver transplantation (LT) in elderly recipients, the proportion of patients continues to increase. This study investigated the outcome of LT in elderly patients (≥ 65 years) in an Italian, multicenter cohort. Between January 2014 and December 2019, 693 eligible patients were transplanted, and two groups were compared: recipients ≥ 65 years (n = 174, 25.1%) versus 50-59 years (n = 519, 74.9%). Confounders were balanced using a stabilized inverse probability therapy weighting (IPTW). Elderly patients showed more frequent early allograft dysfunction (23.9 versus 16.8%, p = 0.04). Control patients had longer posttransplant hospital stays (median: 14 versus 13 days; p = 0.02), while no difference was observed for posttransplant complications (p = 0.20). At multivariable analysis, recipient age ≥ 65 years was an independent risk factor for patient death (HR 1.76; p = 0.002) and graft loss (HR 1.63; p = 0.005). The 3-month, 1-year, and 5-year patient survival rates were 82.6, 79.8, and 66.4% versus 91.1, 88.5, and 82.0% in the elderly and control group, respectively (log-rank p = 0.001). The 3-month, 1-year, and 5-year graft survival rates were 81.5, 78.7, and 66.0% versus 90.2, 87.2, and 79.9% in the elderly and control group, respectively (log-rank p = 0.003). Elderly patients with CIT > 420 min showed 3-month, 1-year, and 5-year patient survival rates of 75.7%, 72.8%, and 58.5% versus 90.4%, 86.5%, and 79.4% for controls (log-rank p = 0.001). LT in elderly (≥ 65 years) recipients provides favorable results, but inferior to those achieved in younger patients (50-59), especially when CIT > 7 h. Containment of cold ischemia time seems pivotal for favorable outcomes in this class of patients.
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Affiliation(s)
- Fabio Melandro
- Sapienza University of Rome, AOU Umberto I Policlinico of Rome, Rome, Italy.
| | - Quirino Lai
- Sapienza University of Rome, AOU Umberto I Policlinico of Rome, Rome, Italy
| | - Davide Ghinolfi
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Via Paradisa 2, 56124, Pisa, Italy
| | - Tommaso Maria Manzia
- Hepatobiliary Surgery and Transplant Unit, Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy
| | - Gabriele Spoletini
- General Surgery and Liver Transplantation, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Massimo Rossi
- Sapienza University of Rome, AOU Umberto I Policlinico of Rome, Rome, Italy
| | - Salvatore Agnes
- General Surgery and Liver Transplantation, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Giuseppe Tisone
- Hepatobiliary Surgery and Transplant Unit, Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy
| | - Paolo De Simone
- Department of Surgical, Medical, Biochemical Pathology and Intensive Care, University of Pisa, Pisa, Italy
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9
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Lv H, Zheng H, Liu J, Cai Q, Ren Y, Yi H, Yang Y, Hu X, Chen G, Transplantation Immunology Committee of Branch of Organ Transplantation Physician of Chinese Medical Doctor Association, Organ Transplant Committee of China Association Rehabilitation Medicine, Guangdong Medical Doctor Association of Organ Transplantation. Expert consensus on liver transplantation perioperative evaluation and rehabilitation for acute-on-chronic liver failure. LIVER RESEARCH 2022; 6:121-129. [PMID: 39958201 PMCID: PMC11791836 DOI: 10.1016/j.livres.2022.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 08/15/2022] [Indexed: 11/15/2022]
Abstract
Acute-on-chronic liver failure (ACLF) can be cured by liver transplantation; however, perioperative complications still affect posttransplant outcomes. In recent years, early rehabilitation for critical illness, liver disease, and surgery have significantly improved organ reserve function, surgery tolerance, and postoperative quality of life. They could also be applied in the perioperative period of liver transplantation in patients with ACLF. Therefore, the Transplantation Immunology Committee of Branch of Organ Transplantation Physician of Chinese Medical Doctor Association, the Organ Transplant Committee of China Association Rehabilitation Medicine, and the Guangdong Medical Doctor Association of Organ Transplantation conducted a comprehensive review of rehabilitation in end-stage liver disease, critical illness and surgical patients by summarizing current evidence and best clinical practices and proposed a practice consensus on evaluation of cardiopulmonary and physical function, rehabilitation or physiotherapies, as well as the safety concerns in perioperative liver transplant recipients. It will be a valuable resource for hepatologists, transplant surgeons, and intensivists as they care for ACLF patients during transplantation.
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Affiliation(s)
- Haijin Lv
- Surgical Intensive Care Unit, Intensive Care Unit of Organ Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Haiqing Zheng
- Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Jianrong Liu
- Surgical Intensive Care Unit, Intensive Care Unit of Organ Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Qing Cai
- Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yuji Ren
- Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Huimin Yi
- Surgical Intensive Care Unit, Intensive Care Unit of Organ Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yang Yang
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xiquan Hu
- Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Guihua Chen
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Transplantation Immunology Committee of Branch of Organ Transplantation Physician of Chinese Medical Doctor Association
- Surgical Intensive Care Unit, Intensive Care Unit of Organ Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Organ Transplant Committee of China Association Rehabilitation Medicine
- Surgical Intensive Care Unit, Intensive Care Unit of Organ Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Guangdong Medical Doctor Association of Organ Transplantation
- Surgical Intensive Care Unit, Intensive Care Unit of Organ Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
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Qazi-Arisar FA, Uchila R, Chen C, Yang C, Chen SY, Karnam RS, Azhie A, Xu W, Galvin Z, Selzner N, Lilly L, Bhat M. Divergent trajectories of lean vs obese non-alcoholic steatohepatitis patients from listing to post-transplant: A retrospective cohort study. World J Gastroenterol 2022; 28:3218-3231. [PMID: 36051335 PMCID: PMC9331521 DOI: 10.3748/wjg.v28.i26.3218] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 04/22/2022] [Accepted: 06/16/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Non-alcoholic steatohepatitis (NASH) cirrhosis is the second most common indication for liver transplantation (LT). The role of body mass index (BMI) on outcomes of NASH cirrhosis has been conflicting.
AIM To compare the longitudinal trajectories of patients with lean vs obese NASH cirrhosis, from listing up to post-transplant, having adjusted their BMI for ascites.
METHODS We retrospectively reviewed all adult NASH patients listed for LT in our program from 2012 to 2019. Fine-Gray Competing Risk analyses and Cox Proportional-Hazard Models were performed to examine the cumulative incidence of transplant and survival outcomes respectively.
RESULTS Out of 265 NASH cirrhosis listed patients, 176 were included. Median age was 61.0 years; 46% were females. 111 patients underwent LT. Obese robust patients had better waitlist survival [hazard ratio (HR): 0.12; 95%CI: 0.05–0.29, P < 0.0001] with higher instantaneous rate of transplant (HR: 5.71; 95%CI: 1.26–25.9, P = 0.02). Lean NASH patients had a substantially higher risk of graft loss within 90 d post-LT (1.2% vs 13.8%, P = 0.032) and death post-LT (2.4% vs 17.2%, P = 0.029). 1- 3- and 5-year graft survival was poor for lean NASH (78.6%, 77.3% and 41.7% vs 98.6%, 96% and 85% respectively). Overall patient survival post-LT was significantly worse in lean NASH (HR: 0.17; 95%CI: 0.03–0.86, P = 0.0142) with 83% lower instantaneous rate of death in obese group.
CONCLUSION Although lean NASH is considered to be more benign than obese NASH, our study suggests a paradoxical correlation of lean NASH with waitlist outcomes, and graft and patient survival post-LT.
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Affiliation(s)
- Fakhar Ali Qazi-Arisar
- Ajmera Transplant Program, Toronto General Hospital, University Health Network, Toronto M5G 2N2, Ontario, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto M5G 2N2, Ontario, Canada
- National Institute of Liver and GI Diseases, Dow University of Health Sciences, Karachi 75330, Pakistan
| | - Raj Uchila
- Ajmera Transplant Program, Toronto General Hospital, University Health Network, Toronto M5G 2N2, Ontario, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto M5G 2N2, Ontario, Canada
| | - Catherine Chen
- Ajmera Transplant Program, Toronto General Hospital, University Health Network, Toronto M5G 2N2, Ontario, Canada
| | - Cathy Yang
- Ajmera Transplant Program, Toronto General Hospital, University Health Network, Toronto M5G 2N2, Ontario, Canada
| | - Shi-Yi Chen
- Department of Biostatistics, Princess Margaret Cancer Center, University Health Network, Toronto M5G 2C1, Ontario, Canada
| | - Ravikiran Sindhuvalada Karnam
- Ajmera Transplant Program, Toronto General Hospital, University Health Network, Toronto M5G 2N2, Ontario, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto M5G 2N2, Ontario, Canada
| | - Amirhossein Azhie
- Ajmera Transplant Program, Toronto General Hospital, University Health Network, Toronto M5G 2N2, Ontario, Canada
| | - Wei Xu
- Department of Biostatistics, Princess Margaret Cancer Center, University Health Network, Toronto M5G 2C1, Ontario, Canada
- Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto M5G 2C1, Ontario, Canada
| | - Zita Galvin
- Ajmera Transplant Program, Toronto General Hospital, University Health Network, Toronto M5G 2N2, Ontario, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto M5G 2N2, Ontario, Canada
| | - Nazia Selzner
- Ajmera Transplant Program, Toronto General Hospital, University Health Network, Toronto M5G 2N2, Ontario, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto M5G 2N2, Ontario, Canada
| | - Leslie Lilly
- Ajmera Transplant Program, Toronto General Hospital, University Health Network, Toronto M5G 2N2, Ontario, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto M5G 2N2, Ontario, Canada
| | - Mamatha Bhat
- Ajmera Transplant Program, Toronto General Hospital, University Health Network, Toronto M5G 2N2, Ontario, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto M5G 2N2, Ontario, Canada
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11
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de Fátima Ribeiro Silva C, Ohara DG, Matos AP, Pinto ACPN, Pegorari MS. Short Physical Performance Battery as a Measure of Physical Performance and Mortality Predictor in Older Adults: A Comprehensive Literature Review. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph182010612. [PMID: 34682359 PMCID: PMC8535355 DOI: 10.3390/ijerph182010612] [Citation(s) in RCA: 81] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 10/05/2021] [Accepted: 10/06/2021] [Indexed: 01/04/2023]
Abstract
The association between the Short Physical Performance Battery (SPPB) score and several adverse health outcomes, including mortality, has been reported in the scientific literature. We conducted a comprehensive literature review of studies on the relationship between SPPB and mortality. The current paper synthesizes the characteristics and main findings of longitudinal studies available in the literature that investigated the role of the SPPB in predicting mortality in older adults. The studies (n = 40) are from North America, South America, Europe, and Asia; the majority (n = 16) were conducted with community-dwelling older adults and reported an association between lower SPPB scores and a higher risk of mortality, and between higher SPPB scores and higher survival. Nevertheless, few studies have analyzed the accuracy of the instrument to predict mortality. The only study that established cut-off points was conducted with older adults discharged from an acute care hospital. Although an SPPB score lower than 10 seems to predict all-cause mortality, further studies showing cut-off points in specific settings and loco-regional specificities are still necessary.
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12
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Ayorinde T, Panayotova G, Sharma A, Lunsford KE. Clinical and biomarker assessment of frailty in liver transplantation. Curr Opin Organ Transplant 2021; 26:488-497. [PMID: 34343156 PMCID: PMC8446327 DOI: 10.1097/mot.0000000000000911] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
PURPOSE OF REVIEW Liver cirrhosis results in progressive decline, or frailty, which leads to poor outcomes and decreased survival. Multiple biomarkers and clinical assessment tools for quantifying frailty in liver transplant candidates exist, but a universal scoring protocol is lacking. Criteria vary between studies and correlation with patient outcome is not always clear. This review aims to summarize the pertinent biomarkers and assessment tools of frailty in cirrhosis. RECENT FINDINGS As cirrhosis progresses, the resultant 'frailty' is an inseparable independent predictor of pre and posttransplant mortality. Pro-inflammatory, neuroendocrine, and adipokine factors are dysregulated - leading to paradoxical anorexia and downregulation of orexigenic signals. The resulting catabolic utilization of amino and fatty acids leads to progressive malnutrition and sarcopenia. Both functional and imaging criteria define sarcopenia in cirrhotic patients, and degree of debilitation correlates with mortality. Liver-disease-specific frailty biomarkers and scoring tools are optimal to assess physical dysfunction in cirrhotics to promote early diagnosis and intervention. SUMMARY Liver cirrhosis and resulting frailty are progressive and portend a poor patient prognosis. A comprehensive, validated algorithm for detecting and quantifying frailty specific to liver disease would allow for standardization and facile application in the clinical setting. Early diagnosis is key for timely intervention and improved patient outcomes.
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Affiliation(s)
- Tumininu Ayorinde
- Division of Transplant and HPB Surgery, Department of Surgery, Rutgers New Jersey Medical School, Newark, NJ
| | - Guergana Panayotova
- Division of Transplant and HPB Surgery, Department of Surgery, Rutgers New Jersey Medical School, Newark, NJ
| | - Aanchal Sharma
- Division of Transplant and HPB Surgery, Department of Surgery, Rutgers New Jersey Medical School, Newark, NJ
| | - Keri E. Lunsford
- Division of Transplant and HPB Surgery, Department of Surgery, Rutgers New Jersey Medical School, Newark, NJ
- Center for Immunity and Inflammation, Institute for Infectious and Inflammatory Diseases, Rutgers New Jersey Medical School, Newark, NJ
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13
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Hakeem AR, Fathima R, Padmanaban H, Haribabu K, Rajalingam R, Palaniappan K, Jothimani D, Kanagavelu R, Rajakumar A, Kaliamoorthy I, Reddy MS, Rela M. Propensity Score-Matched Analysis of Posttransplant Outcomes in Living Donor Liver Transplantation for Older Adult Recipients. Liver Transpl 2021; 27:1273-1282. [PMID: 33787013 DOI: 10.1002/lt.26061] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Revised: 02/15/2021] [Accepted: 03/04/2021] [Indexed: 02/07/2023]
Abstract
The impact of increasing recipient age on morbidity and mortality following living donor liver transplantation (LDLT) remains controversial. The study aims to analyze the impact of recipient age on outcomes following LDLT. Data on adult LDLTs performed between November 2009 and February 2020 were retrieved from a prospectively maintained database. Patients were stratified into 2 groups based on recipient age: 18 to 65 years (younger adults) and >65 years (older adults). Propensity score matching (PSM) using nearest-neighbor matching was used to match each older recipient with up to 2 younger adult recipients using multiple preoperative parameters. Outcomes evaluated were duration of ventilation, need for reintubation, tracheostomy, intensive care unit (ICU) readmission, length of ICU and hospital stays, postoperative complications, reoperation within 90 days, and patient survival. A total of 801 adult LDLT recipients were included in the study; 751 (93.7%) were younger adults, and 50 (6.3%) were older adults. Older recipients were more likely to be diabetic (60.0% versus 39.7%) and hypertensive (44.0% versus 20.4%) with preexisting cardiac disease (28.0% versus 11.2%). However, their pretransplant Model for End-Stage Liver Disease score was significantly lower (14.5 versus 17.7), and they were more likely to receive a transplant because of hepatocellular carcinoma (38.0% versus 17.7%). Older recipients had longer durations of ventilation after LT both before (3.7 versus 1.9 days) and after PSM (4.0 versus 1.5 days). After PSM, the 30-day (13.0% versus 2.4%), 90-day (15.2% and 2.4%), and overall mortality rates (21.7% versus 7.1%) were significantly higher for older recipients when compared with younger recipients. There was no difference between the younger and older recipients with respect to other postoperative outcomes. This propensity score-matched study shows that the older LDLT recipients have higher 30-day, 90-day, 1-year, and 5-year mortality rates when compared with matched younger counterparts.
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Affiliation(s)
- Abdul Rahman Hakeem
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Rukhaiya Fathima
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Hrishikesh Padmanaban
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Kulaseharan Haribabu
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Rajesh Rajalingam
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Kumar Palaniappan
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Dinesh Jothimani
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Rathan Kanagavelu
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Akila Rajakumar
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Ilankumaran Kaliamoorthy
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Mettu Srinivas Reddy
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Mohamed Rela
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
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14
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Puchades Renau L, Herreras López J, Cebrià I Iranzo MÀ, Cezón Serrano N, Berenguer Haym M. Physical frailty in liver transplantation. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2021; 113:533-540. [PMID: 33371691 DOI: 10.17235/reed.2020.7448/2020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
In patients with cirrhosis, frailty represents a status of global physical dysfunction associated with a multiplicity of factors, including muscle wasting, undernutrition and malnutrition, and functional impairment. This condition is particularly prevalent among those with advanced cirrhosis, such as liver transplant (LT) candidates. Studies in this vulnerable population have demonstrated that its presence is independently predictive of adverse outcomes both pre- and post-transplantation, and thus that its incorporation into clinical practice could result in improved clinical decision-making, particularly regarding the identification of candidates for physical and nutritional interventions. There are, however, some limitations to its immediate incorporation into organ allocation prioritization models, including the wide heterogeneity of instruments used for measuring frailty, and particularly the lack of a single one suitable in all LT clinical scenarios (inpatient vs outpatient; pre- vs post-transplant). Finally, the data on the potential effects of frailty improvement on the diverse range of outcome measures are still preliminary.
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Affiliation(s)
- Lorena Puchades Renau
- Grupo de Hepatología y Trasplante Hepático, Instituto de Investigación Sanitaria La Fe, España
| | - Julia Herreras López
- Grupo de Hepatología y Trasplante Hepático, Instituto de Investigación Sanitaria La Fe, España
| | | | - Natalia Cezón Serrano
- Grupo de Hepatología y Trasplante Hepático, Instituto de Investigación Sanitaria La Fe, España
| | - Marina Berenguer Haym
- Grupo de Hepatología y Trasplante Hepático, Instituto de Investigación Sanitaria La Fe, España
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15
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Bhanji RA, Watt KD. Physiologic Reserve Assessment and Application in Clinical and Research Settings in Liver Transplantation. Liver Transpl 2021; 27:1041-1053. [PMID: 33713382 DOI: 10.1002/lt.26052] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Accepted: 03/08/2021] [Indexed: 12/13/2022]
Abstract
Physiologic reserve is an important prognostic indicator. Because of its complexity, no single test can measure an individual's physiologic reserve. Frailty is the phenotypic expression of decreased reserve and portends poor prognosis. Both subjective and objective tools have been used to measure one or more components of physiologic reserve. Most of these tools appear to predict pretransplant mortality, but only some predict posttransplant survival. Incorporation of these measures of physiologic reserve in the clinical and research settings including prediction models are reviewed, and the applicability to patient-related outcomes are discussed. Commonly used tools, in patients with cirrhosis, that have been associated with clinical outcomes were reviewed. The strength of subjective tools lies in low-cost, wide availability, and quick assessments at the bedside. A disadvantage of these tools is the manipulative capacity, restricting their value in allocation processes. The strength of objective tests lies in objective measurements and the ability to measure change. The disadvantages include complexity, increased cost, and limited accessibility. Heterogeneity in the definitions and tools used has prevented further advancement or a clear role in transplant assessment. Consistent use of objective tools, including the 6-minute walk test, gait speed, Liver Frailty Index, or Short Physical Performance Battery, are recommended in clinical and research settings.
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Affiliation(s)
- Rahima A Bhanji
- Division of Gastroenterology (Liver Unit), University of Alberta Hospital, Edmonton, Alberta, Canada
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
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16
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Williams FR, Milliken D, Lai JC, Armstrong MJ. Assessment of the Frail Patient With End-Stage Liver Disease: A Practical Overview of Sarcopenia, Physical Function, and Disability. Hepatol Commun 2021; 5:923-937. [PMID: 34141980 PMCID: PMC8183168 DOI: 10.1002/hep4.1688] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 12/14/2020] [Accepted: 01/24/2021] [Indexed: 12/22/2022] Open
Abstract
Frailty has emerged as a powerful predictor of clinical outcomes (e.g., decompensation, hospitalization, mortality) in patients with end-stage liver disease (ESLD). It is therefore of paramount importance that all patients with ESLD undergo an assessment of frailty, to support life and death decision making (i.e., candidacy for critical care, transplantation) and aid with prioritization of evolving prehabilitation services (i.e., nutrition, physiotherapy, psychotherapy). This article aims to provide a practical overview of the recent advances in the clinical, radiological, and remote assessment tools of the frail patient with ESLD. Historically, clinicians have incorporated an assessment of frailty using the "end-of-the-bed test" or "eyeball test" into their clinical decision making. However, over the last decade, numerous nonspecific and specific tools have emerged. The current evidence supports the use of a combination of simple, user-friendly, objective measures to first identify frailty in ESLD (notably Clinical Frailty Scale, Liver Frailty Index), followed by a combination of serial tools to assess specifically sarcopenia (i.e., muscle ultrasound), physical function (i.e., chair stands, hand grip strength), functional capacity (i.e., 6-minute walk test), and physical disability (i.e., activities of daily living).
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Affiliation(s)
- Felicity R Williams
- National Institute for Health Research Biomedical Research CenterInstitute of Inflammation and AgeingUniversity of BirminghamBirminghamUnited Kingdom.,Liver Transplant UnitQueen Elizabeth University Hospital BirminghamBirminghamUnited Kingdom
| | - Don Milliken
- Department of AnesthesiologyUniversity of CaliforniaSan FranciscoCAUSA
| | - Jennifer C Lai
- Division of Gastroenterology and HepatologyDepartment of MedicineUniversity of CaliforniaSan FranciscoCAUSA
| | - Matthew J Armstrong
- Liver Transplant UnitQueen Elizabeth University Hospital BirminghamBirminghamUnited Kingdom.,National Institute for Health Research Biomedical Research CenterCenter for Liver ResearchUniversity of BirminghamBirminghamUnited Kingdom
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17
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Ivanics T, Abreu P, De Martin E, Sapisochin G. Changing Trends in Liver Transplantation: Challenges and Solutions. Transplantation 2021; 105:743-756. [PMID: 32910093 DOI: 10.1097/tp.0000000000003454] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Despite improvements in postliver transplant outcomes through refinements in perioperative management and surgical techniques, several changing trends in liver transplantation have presented challenges. Mortality on the waitlist remains high. In the United States, Europe, and the United Kingdom, there is an increasing need for liver transplantation, primarily as a result of increased incidence of nonalcoholic steatohepatitis-related cirrhosis and cancer indications. Meanwhile, donor suitability has decreased, as donors are often older and have more comorbidities. Despite a mismatch between organ need and availability, many organs are discarded. Notwithstanding this, many solutions have been developed to overcome these challenges. Innovative techniques in allograft preservation, viability assessment, and reconditioning have allowed the use of suboptimal organs with adequate results. Refinements in surgical procedures, including live donor liver transplantations, have increased the organ pool and are decreasing the time and mortality on the waitlist. Despite many challenges, a similar number of solutions and prospects are on the horizon. This review seeks to explore the changing trends and challenges in liver transplantation and highlight possible solutions and future directions.
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Affiliation(s)
- Tommy Ivanics
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Phillipe Abreu
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Eleonora De Martin
- APHP, Hôpital Paul Brousse, Centre Hépato-Biliaire, INSERM 1193, Université Paris-Sud, DHU Hepatinov, Villejuif, France
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
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18
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Cumulative Deficits Frailty Index Predicts Outcomes for Solid Organ Transplant Candidates. Transplant Direct 2021; 7:e677. [PMID: 34113716 PMCID: PMC8183975 DOI: 10.1097/txd.0000000000001094] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 09/27/2020] [Accepted: 10/13/2020] [Indexed: 12/15/2022] Open
Abstract
Supplemental Digital Content is available in the text. Despite comprehensive multidisciplinary candidacy assessments to determine appropriateness for solid organ transplantation, limitations persist in identifying candidates at risk of adverse outcomes. Frailty measures may help inform candidacy evaluation. Our main objective was to create a solid organ transplant frailty index (FI), using the cumulative deficits model, from data routinely collected during candidacy assessments. Secondary objectives included creating a social vulnerability index (SVI) from assessment data and evaluating associations between the FI and assessment, waitlist, and posttransplant outcomes.
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19
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Abdelbasset WK, Nambi G, Elsayed SH, Moawd SA, Ibrahim AA, Verma A, Tantawy SA, Kamel DM, Saleh AK, Aldhafian OR, Nwihadh NB. Prevalence and Nonpharmacological Interventions for Sarcopenia among Cirrhotic Patients. DISEASE MARKERS 2021; 2021:8866093. [PMID: 33628339 PMCID: PMC7884167 DOI: 10.1155/2021/8866093] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Revised: 01/24/2021] [Accepted: 01/31/2021] [Indexed: 11/18/2022]
Abstract
Sarcopenia is the most common feature of hepatic cirrhosis characterized by progressive loss of muscle mass and function and increases permanently the mortality and morbidity rates among those patients. The incidence of sarcopenia in cirrhotic patients ranged 40-70% associating with impaired quality of life and augmented rates of infection. Based on these issues, this review is aimed at determining the prevalence and main causes of sarcopenia among cirrhotic patients and recognizing the recent diagnostic and physical treatment modalities that prevent risk factors for sarcopenia in those patients. No ideal modality is currently demonstrated for diagnosing sarcopenia in hepatic diseases, particularly cirrhosis; however, recent studies reported different diagnostic modalities for muscle function in different individuals including handgrip strength, skeletal muscle index, six-min walk test, liver frailty index, short physical performance battery, and radiological assessments for quadriceps and psoas muscles. Exercise training and therapeutic nutrition are strongly recommended for controlling sarcopenia in cirrhotic patients. The exercise program is designed and carried out on a frequent basis within an extensive scheduled time aimed at improving functional performance, aerobic capacity, and healthy conditions. Finally, a combination of exercise training and therapeutic nutrition is powerfully recommended to control sarcopenia in cirrhosis.
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Affiliation(s)
- Walid Kamal Abdelbasset
- Department of Health and Rehabilitation Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia
- Department of Physical Therapy, Kasr Al-Aini Hospital, Cairo University, Giza, Egypt
| | - Gopal Nambi
- Department of Health and Rehabilitation Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia
| | - Shereen H. Elsayed
- Department of Rehabilitation Sciences, Faculty of Health and Rehabilitation Sciences, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Samah A. Moawd
- Department of Health and Rehabilitation Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia
- Department of Physical Therapy for Cardiovascular/Respiratory Disorders and Geriatrics, Faculty of Physical Therapy, Cairo University, Giza, Egypt
| | - Ahmed A. Ibrahim
- Department of Physical Therapy, College of Applied Medical Sciences, Ha'il University, Hail, Saudi Arabia
| | - Anju Verma
- Department of Health and Rehabilitation Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia
| | - Sayed A. Tantawy
- Department of Physiotherapy, Centre of Radiation, Oncology and Nuclear Medicine, Cairo University, Giza, Egypt
- Department of Physiotherapy for Integumentary Problems, Faculty of Physical Therapy, Deraya University, Menia, Egypt
| | - Dalia M. Kamel
- Department of Physiotherapy for Women's Health, Faculty of Physical Therapy, Cairo University, Giza, Egypt
| | - Ayman K. Saleh
- Department of Orthopedic Surgery, College of Medicine, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia
- Department of Orthopedic, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Osama R. Aldhafian
- Department of Orthopedic Surgery, College of Medicine, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia
| | - Naif Bin Nwihadh
- Department of Orthopedic Surgery, College of Medicine, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia
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Abstract
Increased life expectancy and advances in the care of chronic liver disease has increased the number of elderly patients needing liver transplant. Organ donation policies prioritize transplant to the sickest. There is an ongoing debate with regard to balancing the principles of equity and utility. Several hospitals have adopted center-specific policies and there has been an increased trend of transplant in elderly patients since 2002. Appropriate patient selection and long-term outcomes in the setting of limited organ availability pose several challenges. This article reviews the data and discusses the pros and cons of transplants in the elderly.
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Affiliation(s)
- Claudia Cottone
- Department of Internal Medicine at Northwestern Medicine McHenry Hospital, Rosalind Franklin University of Medicine and Science, 4309 West Medical Center Drive, McHenry, IL 60050, USA.
| | - Nathalie A Pena Polanco
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, 1120 Northwest 14th Street, Suite 1105, Miami, FL 33136, USA
| | - Kalyan Ram Bhamidimarri
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, 1120 Northwest 14th Street, Suite 1144, Miami, FL 33136, USA
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21
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Kriss M, Biggins SW. Evaluation and selection of the liver transplant candidate: updates on a dynamic and evolving process. Curr Opin Organ Transplant 2021; 26:52-61. [PMID: 33278150 DOI: 10.1097/mot.0000000000000829] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW Although conceptually unchanged, the evaluation and selection of the liver transplant candidate has seen significant recent advances. Expanding criteria for transplant candidacy, improved diagnostics for risk stratification and advances in prognostic models have paralleled recent changes in allocation and distribution that require us to revisit core concepts of candidate evaluation and selection while recognizing its now dynamic and continuous nature. RECENT FINDINGS The liver transplant evaluation revolves around three interrelated themes: candidate selection, donor selection and transplant outcome. Introduction of dynamic frailty indices, bariatric surgery at the time of liver transplant in obese patients and improved therapies and prognostic tools for hepatobiliary malignancy have transformed candidate selection. Advances in hypothermic organ preservation have improved outcomes in marginal donor organs. Combined with expansion of hepatitis C virus positive and split donor organs, donor selection has become an integral part of candidate evaluation. In addition, with liver transplant for acute alcohol-related hepatitis now widely performed and increasing recognition of acute-on-chronic liver failure, selection of critically ill patients is refining tools to balance futility versus utility. SUMMARY Advances in liver transplant candidate evaluation continue to transform the evaluation process and require continued incorporation into our clinical practice amidst a dynamic backdrop of demographic and policy changes.
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Affiliation(s)
- Michael Kriss
- Division of Gastroenterology & Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Scott W Biggins
- Division of Gastroenterology and Hepatology
- Center for Liver Investigation Fostering discovEry (C-LIFE), University of Washington, Seattle, Washington, USA
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22
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Haugen CE, McAdams-DeMarco M, Verna EC, Rahimi RS, Kappus MR, Dunn MA, Volk ML, Gurakar A, Duarte-Rojo A, Ganger DR, O'Leary JG, Ladner D, Garonzik-Wang J, Segev DL, Lai JC. Association Between Liver Transplant Wait-list Mortality and Frailty Based on Body Mass Index. JAMA Surg 2020; 154:1103-1109. [PMID: 31509169 DOI: 10.1001/jamasurg.2019.2845] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Importance Among liver transplant candidates, obesity and frailty are associated with increased risk of death while they are on the wait-list. However, use of body mass index (BMI) may not detect candidates at a higher risk of death owing to the fact that ascites and muscle wasting are seen across transplant candidates of all BMI measurements. Objective To evaluate whether the association between wait-list mortality and frailty varied by BMI of liver transplant candidates. Design, Setting, and Participants A prospective cohort study was conducted at 9 liver transplant centers in the United States from March 1, 2012, to May 1, 2018, among 1108 adult liver transplant candidates without hepatocellular carcinoma. Exposures At outpatient evaluation, the Liver Frailty Index score was calculated (grip strength, chair stands, and balance), with frailty defined as a Liver Frailty Index score of 4.5 or more. Candidates' BMI was categorized as nonobese (18.5-29.9), class 1 obesity (30.0-34.9), and class 2 or greater obesity (≥35.0). Main Outcomes and Measures The risk of wait-list mortality was quantified using competing risks regression by candidate frailty, adjusting for age, sex, race/ethnicity, Model for End-stage Liver Disease Sodium score, cause of liver disease, and ascites, including an interaction with candidate BMI. Results Of 1108 liver transplant candidates (474 women and 634 men; mean [SD] age, 55 [10] years), 290 (26.2%) were frail; 170 of 670 nonobese candidates (25.4%), 64 of 246 candidates with class 1 obesity (26.0%), and 56 of 192 candidates with class 2 or greater obesity (29.2%) were frail (P = .57). Frail nonobese candidates and frail candidates with class 1 obesity had a higher risk of wait-list mortality compared with their nonfrail counterparts (nonobese candidates: adjusted subhazard ratio, 1.54; 95% CI, 1.02-2.33; P = .04; and candidates with class 1 obesity: adjusted subhazard ratio, 1.72; 95% CI, 0.99-2.99; P = .06; P = .75 for interaction). However, frail candidates with class 2 or greater obesity had a 3.19-fold higher adjusted risk of wait-list mortality compared with nonfrail candidates with class 2 or greater obesity (95% CI, 1.75-5.82; P < .001; P = .047 for interaction). Conclusions and Relevance This study's finding suggest that among nonobese liver transplant candidates and candidates with class 1 obesity, frailty was associated with a 2-fold higher risk of wait-list mortality. However, the mortality risk associated with frailty differed for candidates with class 2 or greater obesity, with frail candidates having a more than 3-fold higher risk of wait-list mortality compared with nonfrail patients. Frailty assessments may help to identify vulnerable patients, particularly those with a BMI of 35.0 or more, in whom a clinician's visual evaluation may be less reliable to assess muscle mass and nutritional status.
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Affiliation(s)
- Christine E Haugen
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Mara McAdams-DeMarco
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland
| | - Elizabeth C Verna
- Center for Liver Disease and Transplantation, Columbia University Medical Center, New York, New York
| | - Robert S Rahimi
- Department of Hepatology, Baylor University Medical Center, Dallas, Texas
| | - Matthew R Kappus
- Department of Medicine, Duke University School of Medicine, Durham, North Carolina
| | - Michael A Dunn
- Center for Liver Diseases, Thomas A. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Michael L Volk
- Division of Gastroenterology and Hepatology, Loma Linda University Health, Loma Linda, California
| | - Ahmet Gurakar
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Andres Duarte-Rojo
- Division of Gastroenterology and Hepatology, University of Arkansas Medical School, Little Rock
| | - Daniel R Ganger
- Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Jacqueline G O'Leary
- Division of Hepatology, Dallas Veterans Administration Medical Center, Dallas, Texas
| | - Daniela Ladner
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | | | - Dorry L Segev
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland
| | - Jennifer C Lai
- Department of Medicine, University of California, San Francisco
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23
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Multicenter Study of Age, Frailty, and Waitlist Mortality Among Liver Transplant Candidates. Ann Surg 2020; 271:1132-1136. [PMID: 30672803 DOI: 10.1097/sla.0000000000003207] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To determine if the association of frailty and waitlist mortality varies by candidate age. BACKGROUND Frailty, a construct developed in geriatrics, is a state of decreased physiologic reserve, and is associated with mortality while awaiting liver transplantation (LT). However, older candidates have high comorbidity burden and less physiologic reserve, so the relationship between frailty and waitlist mortality may vary by candidate age. METHODS We studied adults listed for LT at 2 transplant centers. The liver frailty index (grip strength, chair stands, balance) was measured at evaluation, with frailty defined as liver frailty index ≥ 4.5. We compared the prevalence of frailty in older (≥65 yr) and younger (18-64 yr) candidates. We studied the association between frailty, age, interaction between the 2, and waitlist mortality using competing risks regression adjusted for sex, BMI, and MELDNa. RESULTS Among 882 LT candidates, 16.6% were ≥ 65 years. Older candidates were more likely to be frail (33.3% vs 21.7%, P = 0.002). Older age [adjusted subhazard ratio (aSHR): 2.16, 95% CI: 1.51-3.09, P < 0.001] and frailty (aSHR: 1.92, 95% CI: 1.38-2.67, P < 0.001) were independently associated with higher risk of waitlist mortality. However, the association between waitlist mortality and frailty did not vary by candidate age (aSHR of frailty for younger patients: 1.90, 95% CI: 1.28-2.80, P = 0.001; aSHR of frailty for older patients: 1.98, 95% CI: 1.07-3.67, P = 0.03; P interaction = 0.9). CONCLUSIONS Older candidates experienced higher rates of frailty than younger candidates. However, regardless of age, frailty was associated with nearly 2-fold increased risk of waitlist mortality. Our data support the applicability of the frailty concept to the whole LT population and can guide the development of prehabilitation programs targeting frailty in LT patients of all ages.
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24
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Gómez-Gavara C, Charco R, Tapiolas I, Ridaura N, Campos-Varela I, Dopazo C, Pando E, Caralt M, Hidalgo E, Castells L, Bilbao I. Recipient Age for Liver Transplantation: Should It Be Limited? A Propensity Score Matching Analysis of a Large European Series. Transplant Proc 2020; 52:1442-1449. [PMID: 32387080 DOI: 10.1016/j.transproceed.2020.02.061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Accepted: 02/05/2020] [Indexed: 11/28/2022]
Abstract
BACKGROUND AND AIMS The demand for older patients not to be denied access to liver transplantation (LT) has intensified as the European population continues to live longer and maintains better health. AIM This study aims to ascertain the impact of recipient age on the post-LT survival in 2 well-balanced populations at Vall d'Hebron University Hospital. METHODS From January 1990 to December 2016, LT recipients (young group: 50-65 years of age; elderly group: >65 years of age) were compared by means of a propensity score matching (PSM) method. RESULTS Prior to PSM, graft survival and patient survival were worse for the elderly group (P < .001). In 1126 LT recipients, a caliper width of 0.01 was used based on the donor (age, sex, cause of donor death, and donor intensive care unit stay) and recipient covariates (sex, body mass index, indication for LT, intraoperative blood transfusion, cardiovascular risk factors, and Model for End-Stage Liver Disease [MELD]-Era). After PSM, 206 patients were matched; 1-, 5-, and 10-year patient survival rates were 77%, 63%, and 52% vs 80%, 64%, and 45% (P = .50) for young vs elderly recipients, respectively. Similar graft survival rates were observed in both groups (P = .42). CONCLUSIONS Advanced age alone should not exclude patients from LT.
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Affiliation(s)
- Concepción Gómez-Gavara
- Department of HPB Surgery and Transplantation, Vall d'Hebron University Hospital, Barcelona, Spain.
| | - Ramón Charco
- Department of HPB Surgery and Transplantation, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Ingrid Tapiolas
- Department of HPB Surgery and Transplantation, Vall d'Hebron University Hospital, Barcelona, Spain; Autonoma University Barcelona, Barcelona, Spain
| | - Núria Ridaura
- Department of HPB Surgery and Transplantation, Vall d'Hebron University Hospital, Barcelona, Spain; Autonoma University Barcelona, Barcelona, Spain
| | - Isabel Campos-Varela
- Liver Unit, Department of Internal Medicine, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Cristina Dopazo
- Department of HPB Surgery and Transplantation, Vall d'Hebron University Hospital, Barcelona, Spain; Autonoma University Barcelona, Barcelona, Spain
| | - Elizabeth Pando
- Department of HPB Surgery and Transplantation, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Mireia Caralt
- Department of HPB Surgery and Transplantation, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Ernest Hidalgo
- Department of HPB Surgery and Transplantation, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Lluís Castells
- Liver Unit, Department of Internal Medicine, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Itxarone Bilbao
- Department of HPB Surgery and Transplantation, Vall d'Hebron University Hospital, Barcelona, Spain; Autonoma University Barcelona, Barcelona, Spain
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25
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Dolnikov S, Adam R, Cherqui D, Allard MA. Liver transplantation in elderly patients: what do we know at the beginning of 2020? Surg Today 2020; 50:533-539. [PMID: 32279191 PMCID: PMC7239827 DOI: 10.1007/s00595-020-01996-7] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Accepted: 03/06/2020] [Indexed: 02/07/2023]
Abstract
An aging population has prompted us to evaluate the indications of liver transplantation (LT) in elderly patients more frequently. In this review, we summarize the short- and long-term results after LT in elderly patients and also discuss the criteria used to select patients and how recipient age can challenge current allocation systems. Briefly, the feasibility and early outcomes of LT in elderly patients compare favorably with those of younger patients. Although long-term survival is less than satisfactory, large-scale studies show that the transplant survival benefit is similar for elderly and younger patients. Therefore, age alone does not contraindicate LT; however, screening for cardiopulmonary comorbidities, and asymptomatic malignancies, evaluating nutritional status, and frailty, is crucial to ensure optimal results and avoid futile transplantation.
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Affiliation(s)
- Shimon Dolnikov
- Centre Hépatobiliaire, Paul Brousse Hospital, 14 avenue Paul Vaillant Couturier, 94800, Villejuif, France
| | - René Adam
- Centre Hépatobiliaire, Paul Brousse Hospital, 14 avenue Paul Vaillant Couturier, 94800, Villejuif, France
| | - Daniel Cherqui
- Centre Hépatobiliaire, Paul Brousse Hospital, 14 avenue Paul Vaillant Couturier, 94800, Villejuif, France
| | - Marc Antoine Allard
- Centre Hépatobiliaire, Paul Brousse Hospital, 14 avenue Paul Vaillant Couturier, 94800, Villejuif, France.
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26
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Shah VH, Rao MK. Changing Landscape of Solid Organ Transplantation for Older Adults: Trends and Post-Transplant Age-Related Outcomes. CURRENT TRANSPLANTATION REPORTS 2020. [DOI: 10.1007/s40472-020-00275-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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27
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Sinclair M. Controversies in Diagnosing Sarcopenia in Cirrhosis-Moving from Research to Clinical Practice. Nutrients 2019; 11:2454. [PMID: 31615103 PMCID: PMC6836123 DOI: 10.3390/nu11102454] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Revised: 10/07/2019] [Accepted: 10/10/2019] [Indexed: 02/07/2023] Open
Abstract
Sarcopenia, defined as loss of muscle mass and function, is increasingly recognized as a common consequence of advanced cirrhosis that is associated with adverse clinical outcomes. Despite the recent proliferation in publications pertaining to sarcopenia in end-stage liver disease, there remains no single 'best method' for its diagnosis. The inability to identify a gold standard is common to other specialties, including geriatrics from which many diagnostic tools are derived. Controversies in diagnosis have implications for the accuracy and reproducibility of cohort studies in the field, largely prohibit the introduction of sarcopenia measurement into routine patient care and impede the development of clinical trials to identify appropriate therapies. Difficulties in diagnosis are partly driven by our ongoing limited understanding of the pathophysiology of sarcopenia in cirrhosis, the mechanisms by which it impacts on patient outcomes, the heterogeneity of patient populations, and the accuracy, availability and cost of assessments of muscle mass and function. This review discusses the currently studied diagnostic methods for sarcopenia in cirrhosis, and outlines why reaching a consensus on sarcopenia diagnosis is important and suggests potential ways to improve diagnostic criteria to allow us to translate sarcopenia research into improvements in clinical care.
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Affiliation(s)
- Marie Sinclair
- Department of Medicine, The University of Melbourne, Parkville 3050, Australia.
- Austin Health, Liver Transplant Unit, 145 Studley Road, Heidelberg 3084, Australia.
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28
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Abstract
The average age of liver transplant donors and recipients has increased over the years. Independent of the cause of liver disease, older candidates have more comorbidities, higher waitlist mortality and higher post-transplant mortality than younger patients. However, transplant benefit may be similar in older and younger recipients, provided older recipients are carefully selected. The cohort of elderly patients transplanted decades ago is also increasingly raising issues concerning long-term exposure to immunosuppression and aging of the transplanted liver. Excellent results can be achieved with elderly donors and there is virtually no upper age limit for donors after brain death liver transplantation. The issue is how to optimise selection, procurement and matching to ensure good results with elderly donors. The impact of old donor age is more pronounced in younger recipients and patients with a high model for end-stage liver disease score. Age matching between the donor and the recipient should be incorporated into allocation policies with a multistep approach. However, age matching may vary depending on the objectives of different allocation policies. In addition, age matching must be revisited in the era of direct-acting antivirals. More restrictive limits have been adopted in donation after circulatory death. Perfusion machines which are currently under investigation may help expand these limits. In living donor liver transplantation, donor age limit is essentially guided by morbidity related to procurement. In this review we summarise changing trends in recipient and donor age. We discuss the implications of older age donors and recipients. We also consider different options for age matching in liver transplantation that could improve outcomes.
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Murphy SL, Tapper EB, Blackwood J, Richardson JK. Why Do Individuals with Cirrhosis Fall? A Mechanistic Model for Fall Assessment, Treatment, and Research. Dig Dis Sci 2019; 64:316-323. [PMID: 30327964 DOI: 10.1007/s10620-018-5333-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 10/09/2018] [Indexed: 12/12/2022]
Abstract
Falls are prevalent for people with cirrhosis and commonly lead to loss of independence, reduced quality of life, and mortality. Despite a critical need for fall prevention in this population, cirrhosis-specific fall-related mechanisms are not well understood. We posit that most falls in this patient population are due to a coalescence of discrete subclinical impairments that are not typically detected at the point of care. The combined effect of these subtle age- and disease-related neurocognitive and muscular impairments leads to the inability to respond successfully to a postural perturbation within the available 300 to 400 ms. This article provides a conceptual model of physiological resilience to avoid a fall that focuses on attributes that underlie the ability to withstand a postural perturbation and their clinical evaluation. Evidence supporting this model in cirrhosis and other high fall risk conditions will be synthesized and suggestions for fall assessment and treatment will be discussed.
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Affiliation(s)
- Susan L Murphy
- Department of Physical Medicine and Rehabilitation, University of Michigan, 24 Frank Lloyd Wright Drive, PO Box 344, Ann Arbor, MI, 48106, USA. .,Geriatric Research, Education and Clinical Center, Veterans Affairs Ann Arbor Health Care System, Ann Arbor, MI, USA.
| | - Elliot B Tapper
- Department of Internal Medicine, Division of Gasteroenterology, University of Michigan, Ann Arbor, MI, USA. .,Veterans Affairs Ann Arbor Health Care System, Ann Arbor, MI, USA.
| | - Jennifer Blackwood
- Department of Physical Therapy, University of Michigan - Flint Campus, Flint, MI, USA
| | - James K Richardson
- Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, USA
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Liu R, Ahluwalia V, Kang JD, Ghosh SS, Zhou H, Li Y, Zhao D, Gurley E, Li X, White MB, Fagan A, Lippman HR, Wade JB, Hylemon PB, Bajaj JS. Effect of Increasing Age on Brain Dysfunction in Cirrhosis. Hepatol Commun 2019; 3:63-73. [PMID: 30619995 PMCID: PMC6312655 DOI: 10.1002/hep4.1286] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Accepted: 10/24/2018] [Indexed: 12/28/2022] Open
Abstract
Patients with cirrhosis are growing older, which could have an impact on brain dysfunction beyond hepatic encephalopathy. Our aim was to study the effect of concomitant aging and cirrhosis on brain inflammation and degeneration using human and animal experiments. For the human study, age-matched patients with cirrhosis and controls between 65 and 85 years underwent cognitive testing, quality of life (QOL) assessment, and brain magnetic resonance (MR) spectroscopy and resting state functional MR imaging (rs-fMRI) analysis. Data were compared between groups. For the animal study, young (10-12 weeks) and old (1.5 years) C57BL/6 mice were given either CCl4 gavage to develop cirrhosis or a vehicle control and were followed for 12 weeks. Cortical messenger RNA (mRNA) expression of inflammatory mediators (interleukin [IL]-6, IL-1β, transforming growth factor β [TGF-β], and monocyte chemoattractant protein 1), sirtuin-1, and gamma-aminobutyric acid (GABA)-ergic synaptic plasticity (neuroligin-2 [NLG2], discs large homolog 4 [DLG4], GABA receptor, subunit gamma 1/subunit B1 [GABRG1/B1]) were analyzed and compared between younger/older control and cirrhotic mice. The human study included 46 subjects (23/group). Patients with cirrhosis had worse QOL and cognition. On MR spectroscopy, patients with cirrhosis had worse changes related to ammonia and lower N-acetyl aspartate, whereas rs-fMRI analysis revealed that these patients demonstrated functional connectivity changes in the frontoparietal cortical region compared to controls. Results of the animal study showed that older mice required lower CCl4 to reach cirrhosis. Older mice, especially with cirrhosis, demonstrated higher cortical inflammatory mRNA expression of IL-6, IL-1β, and TGF-β; higher glial and microglial activation; and lower sirtuin-1 expression compared to younger mice. Older mice also had lower expression of DLG4, an excitatory synaptic organizer, and higher NLG2 and GABRG1/B1 receptor expression, indicating a predominantly inhibitory synaptic organization. Conclusion: Aging modulates brain changes in cirrhosis; this can affect QOL, cognition, and brain connectivity. Cortical inflammation, microglial activation, and altered GABA-ergic synaptic plasticity could be contributory.
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Affiliation(s)
- Runping Liu
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth UniversityRichmondVA
- Microbiology and ImmunologyVirginia Commonwealth UniversityRichmondVA
- Hunter Holmes McGuire Veterans Administration Medical CenterVirginia Commonwealth UniversityRichmondVA
| | - Vishwadeep Ahluwalia
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth UniversityRichmondVA
- Hunter Holmes McGuire Veterans Administration Medical CenterVirginia Commonwealth UniversityRichmondVA
| | - Jason D. Kang
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth UniversityRichmondVA
- Microbiology and ImmunologyVirginia Commonwealth UniversityRichmondVA
- Hunter Holmes McGuire Veterans Administration Medical CenterVirginia Commonwealth UniversityRichmondVA
| | - Siddhartha S. Ghosh
- Hunter Holmes McGuire Veterans Administration Medical CenterVirginia Commonwealth UniversityRichmondVA
- Division of NephrologyVirginia Commonwealth UniversityRichmondVA
| | - Huiping Zhou
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth UniversityRichmondVA
- Microbiology and ImmunologyVirginia Commonwealth UniversityRichmondVA
- Hunter Holmes McGuire Veterans Administration Medical CenterVirginia Commonwealth UniversityRichmondVA
| | - Yunzhou Li
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth UniversityRichmondVA
- Microbiology and ImmunologyVirginia Commonwealth UniversityRichmondVA
- Hunter Holmes McGuire Veterans Administration Medical CenterVirginia Commonwealth UniversityRichmondVA
| | - Derrick Zhao
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth UniversityRichmondVA
- Microbiology and ImmunologyVirginia Commonwealth UniversityRichmondVA
- Hunter Holmes McGuire Veterans Administration Medical CenterVirginia Commonwealth UniversityRichmondVA
| | - Emily Gurley
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth UniversityRichmondVA
- Microbiology and ImmunologyVirginia Commonwealth UniversityRichmondVA
- Hunter Holmes McGuire Veterans Administration Medical CenterVirginia Commonwealth UniversityRichmondVA
| | - Xiaojiaoyang Li
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth UniversityRichmondVA
- Microbiology and ImmunologyVirginia Commonwealth UniversityRichmondVA
- Hunter Holmes McGuire Veterans Administration Medical CenterVirginia Commonwealth UniversityRichmondVA
| | - Melanie B. White
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth UniversityRichmondVA
- Hunter Holmes McGuire Veterans Administration Medical CenterVirginia Commonwealth UniversityRichmondVA
| | - Andrew Fagan
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth UniversityRichmondVA
- Hunter Holmes McGuire Veterans Administration Medical CenterVirginia Commonwealth UniversityRichmondVA
| | - H. Robert Lippman
- Hunter Holmes McGuire Veterans Administration Medical CenterVirginia Commonwealth UniversityRichmondVA
- PathologyVirginia Commonwealth UniversityRichmondVA
| | - James B. Wade
- PsychiatryVirginia Commonwealth UniversityRichmondVA
| | - Phillip B. Hylemon
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth UniversityRichmondVA
- Microbiology and ImmunologyVirginia Commonwealth UniversityRichmondVA
- Hunter Holmes McGuire Veterans Administration Medical CenterVirginia Commonwealth UniversityRichmondVA
| | - Jasmohan S. Bajaj
- Division of Gastroenterology, Hepatology, and NutritionVirginia Commonwealth UniversityRichmondVA
- Hunter Holmes McGuire Veterans Administration Medical CenterVirginia Commonwealth UniversityRichmondVA
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Haugen CE, Holscher CM, Garonzik-Wang J, Pozo M, Warsame F, McAdams-DeMarco M, Segev DL. National Trends in Liver Transplantation in Older Adults. J Am Geriatr Soc 2018; 66:2321-2326. [PMID: 30325004 PMCID: PMC6289760 DOI: 10.1111/jgs.15583] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Revised: 07/27/2018] [Accepted: 07/31/2018] [Indexed: 12/29/2022]
Abstract
OBJECTIVES To explore trends in liver transplantation (LT) and outcomes for older recipients for evaluation, counseling, and appropriate referral of this vulnerable group of older adults. DESIGN Prospective national cohort study. SETTING Scientific Registry of Transplant Recipients (January 1, 2003-December 31, 2016). PARTICIPANTS Older (aged ≥ 65) deceased donor liver-only transplant recipients (n=8,627). MEASUREMENTS We evaluated temporal changes in recipient, donor, and transplant characteristics and post-LT length of stay (LOS), acute rejection, graft loss, and mortality using logistic regression and Cox proportional hazards. RESULTS LT in older adults almost quadrupled, from 263 in 2003 (9.5% of total LTs that year) to 1,144 in 2016 (20.7% of total LTs). Recent recipients were more likely to be female and African American and have a higher body mass index and Model for End-Stage Liver Disease score. Hepatitis C, nonalcoholic steatohepatitis, and hepatocellular carcinoma were the most common indications for LT in recent recipients. Odds of LOS longer than 2 weeks decreased 34% from 2003-06 to 2013-16 (adjusted odds ratio (aOR)=0.66, 95% confidence interval (CI)=0.57-0.76, P < .001), 1-year acute rejection decreased 30% (aOR=0.70, 95% CI=0.56-0.88, P = .002), all-cause graft loss decreased 54% (adjusted hazard ratio (aHR)=0.46, 95% CI=0.40-0.52, P < .001), and mortality decreased 57% (aHR=0.43, 95% CI=0.38-0.49, P < .001). CONCLUSION Despite the substantial increase in the number of older adults undergoing LT and the severity of their condition, LOS, rejection, graft loss, and mortality have significantly decreased over time. These trends can help guide appropriate LT referral and counseling in older adults with end-stage liver disease. J Am Geriatr Soc 66:2321-2326, 2018.
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Affiliation(s)
- Christine E Haugen
- Department of Surgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Courtenay M Holscher
- Department of Surgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland
| | | | - Marcos Pozo
- Department of Surgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Fatima Warsame
- Department of Surgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Mara McAdams-DeMarco
- Department of Surgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
| | - Dorry L Segev
- Department of Surgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
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Nastasi AJ, Bryant TS, Le JT, Schrack J, Ying H, Haugen CE, Fernández MG, Segev DL, McAdams-DeMarco MA. Pre-kidney transplant lower extremity impairment and transplant length of stay: a time-to-discharge analysis of a prospective cohort study. BMC Geriatr 2018; 18:246. [PMID: 30340462 PMCID: PMC6194663 DOI: 10.1186/s12877-018-0940-y] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2017] [Accepted: 10/09/2018] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Few objective tests can be performed at admission for kidney transplantation [KT] to discern risk of increased length of stay [LOS], which is important for patient counseling and is associated with increased costs and mortality. The short physical performance battery [SPPB] is an easily administered, potentially modifiable, 3-part test of lower extremity function. SPPB score is associated with longer hospital LOS in older adults, and may provide similar utility in KT recipients given that ESRD is a disease of accelerated aging. The aim of this study was to characterize the association between SPPB-derived lower extremity function and LOS. METHODS The SPPB was administered at KT admission in a prospective cohort of 595 recipients (8/2009-6/2016). The independent association between SPPB impairment (score ≤ 10) and LOS was tested with an adjusted conventional generalized gamma parametric survival model. RESULTS Impaired recipients experienced longer LOS (median: 10 vs. 8 days; P < 0.001) with the greatest difference in percent discharged on day 10 (impaired: 54.5%, unimpaired: 73.3%). Discharge typically took 13% longer in the impaired group (relative time = 1.13; 95%CI: 1.05, 1.21, P = 0.001). Discharge for impaired recipients compared to unimpaired was least likely at day 5 (hazard ratio = 0.71; 95% CI:0.68, 0.74, P < 0.001). No differences in the SPPB impairment-LOS relationship were found by age (interaction P = 0.74). CONCLUSIONS Pre-KT SPPB impairment was independently associated with longer LOS regardless of age, indicating that it is a useful, objective tool for pre-KT risk assessment in younger and older recipients that may help inform discharge planning.
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Affiliation(s)
- Anthony J. Nastasi
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Baltimore, MD 21205 USA
- Department of Surgery, Johns Hopkins School of Medicine, Baltimore, MD USA
| | - Tyler S. Bryant
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Baltimore, MD 21205 USA
| | - Jimmy T. Le
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Baltimore, MD 21205 USA
| | - Jennifer Schrack
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Baltimore, MD 21205 USA
| | - Hao Ying
- Department of Surgery, Johns Hopkins School of Medicine, Baltimore, MD USA
| | | | - Marlís González Fernández
- Department of Physical Medicine and Rehabilitation, Johns Hopkins University School of Medicine, Baltimore, MD USA
| | - Dorry L. Segev
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Baltimore, MD 21205 USA
- Department of Surgery, Johns Hopkins School of Medicine, Baltimore, MD USA
| | - Mara A. McAdams-DeMarco
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Baltimore, MD 21205 USA
- Department of Surgery, Johns Hopkins School of Medicine, Baltimore, MD USA
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Henson JB, Patel YA, Wilder JM, Zheng J, Chow SC, King LY, Muir AJ. Differences in Phenotypes and Liver Transplantation Outcomes by Age Group in Patients with Primary Sclerosing Cholangitis. Dig Dis Sci 2017; 62:3200-3209. [PMID: 28391417 PMCID: PMC5861350 DOI: 10.1007/s10620-017-4559-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2017] [Accepted: 03/28/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND There is increasing evidence for a heterogeneity of phenotypes in primary sclerosing cholangitis (PSC), but differences across the age spectrum in adults with PSC have not been well characterized. AIMS To characterize phenotypic variations and liver transplantation outcomes by age group in adults with PSC. METHODS The United Network for Organ Sharing database was used to identify waitlist registrations for primary liver transplantation in adults with PSC. Patients were split into three age groups: 18-39 (young), 40-59 (middle-aged), and ≥60 (older). Their clinical characteristics and outcomes on the waitlist and post-transplant were compared. RESULTS Overall, 8272 adults with PSC were listed for liver transplantation during the study period, of which 28.9% were young, 52.0% were middle-aged, and 19.1% were older. The young age group had the greatest male predominance (70.0 vs. 66.2 vs. 65.1%, p = 0.001), the highest proportion of black individuals (20.0 vs. 11.0 vs. 5.5%, p < 0.001), and the most patients listed with concomitant autoimmune hepatitis (2.2 vs. 1.0 vs. 0.8%, p < 0.001). Older patients experienced the greatest waitlist and post-transplant mortality. Graft survival was greatest in the middle-aged group. Young patients were most likely to experience acute rejection (31 vs. 22.8 vs. 18.0%, p < 0.001) and have graft failure due to chronic rejection or PSC recurrence (47.8 vs. 42.3 vs. 17.9%, p < 0.001). CONCLUSIONS Age-related differences exist among adults with PSC and are associated with outcomes pre- and post-transplant. Young patients may have a more robust immune-related phenotype that is associated with poorer graft survival. Future studies are needed to further investigate these findings.
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Affiliation(s)
| | - Yuval A Patel
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA
| | - Julius M Wilder
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA
- Duke Clinical Research Institute, Durham, NC, USA
| | - Jiayin Zheng
- Department of Biostatistics, Duke University School of Medicine, Durham, NC, USA
| | - Shein-Chung Chow
- Department of Biostatistics, Duke University School of Medicine, Durham, NC, USA
- Duke Clinical Research Institute, Durham, NC, USA
| | - Lindsay Y King
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA
| | - Andrew J Muir
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
- Duke Clinical Research Institute, Durham, NC, USA.
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Elderly patients have an altered gut-brain axis regardless of the presence of cirrhosis. Sci Rep 2016; 6:38481. [PMID: 27922089 PMCID: PMC5138827 DOI: 10.1038/srep38481] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2016] [Accepted: 11/10/2016] [Indexed: 02/07/2023] Open
Abstract
Cognitive difficulties manifested by the growing elderly population with cirrhosis could be amnestic (memory-related) or non-amnestic (memory-unrelated). The underlying neuro-biological and gut-brain changes are unclear in this population. We aimed to define gut-brain axis alterations in elderly cirrhotics compared to non-cirrhotic individuals based on presence of cirrhosis and on neuropsychological performance. Age-matched outpatients with/without cirrhosis underwent cognitive testing (amnestic/non-amnestic domains), quality of life (HRQOL), multi-modal MRI (fMRI go/no-go task, volumetry and MR spectroscopy), blood (inflammatory cytokines) and stool collection (for microbiota). Groups were studied based on cirrhosis/not and also based on neuropsychological performance (amnestic-type, amnestic/non-amnestic-type and unimpaired). Cirrhotics were impaired on non-amnestic and selected amnestic tests, HRQOL and systemic inflammation compared to non-cirrhotics. Cirrhotics demonstrated significant changes on MR spectroscopy but not on fMRI or volumetry. Correlation networks showed that Lactobacillales members were positively while Enterobacteriaceae and Porphyromonadaceae were negatively linked with cognition. Using the neuropsychological classification amnestic/non-amnestic-type individuals were majority cirrhosis and had worse HRQOL, higher inflammation and decreased autochthonous taxa relative abundance compared to the rest. This classification also predicted fMRI, MR spectroscopy and volumetry changes between groups. We conclude that gut-brain axis alterations may be associated with the type of neurobehavioral decline or inflamm-aging in elderly cirrhotic subjects.
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Prehabilitation in our most frail surgical patients: are wearable fitness devices the next frontier? Curr Opin Organ Transplant 2016; 21:188-93. [PMID: 26859220 DOI: 10.1097/mot.0000000000000295] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
PURPOSE OF REVIEW Frailty is the concept of accumulating physiologic declines that make people less able to deal with stressors, including surgery. Prehabilitation is intervention to enhance functional capacity before surgery. Frailty and prehabilitation among transplant populations and the role of wearable fitness tracking devices (WFTs) in delivering fitness-based interventions will be discussed. RECENT FINDINGS Frailty is associated with increased complications, longer length of hospital stay and increased mortality after surgery. Frail kidney transplant patients have increased delayed graft function, mortality and early hospital readmission. Frail lung or liver transplant patients are more likely to delist or die on the waitlist. Prehabilitation can mitigate frailty and has resulted in decreased length of hospital stay and fewer postsurgical complications among a variety of surgical populations. Increasingly, WFTs are used to monitor patient activity and improve patient health. Interventions using WFTs have resulted in improved activity, weight loss and blood pressure. SUMMARY Frailty is a measurable parameter that identifies patients at risk for worse health outcomes and can be mitigated through intervention. Prehabilitation to reduce frailty has been shown to improve postsurgical outcomes in a variety of populations. WFTs are being integrated in healthcare delivery for monitoring and changing health behavior with promising results.
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Abstract
PURPOSE OF REVIEW The most difficult, and perhaps, most important decision that a clinician makes for a patient on the liver transplant wait-list is when 'not' to proceed with liver transplant. Although an individual may be suitable for transplant surgery at listing, he/she may become too sick while waiting. RECENT FINDINGS This article reviews four specific conditions that commonly arise on the wait-list that may render a candidate too sick for transplant: advancing age, sarcopenia, acute on chronic liver failure, and nonliver-related medical comorbidities. Each condition, per se, is often not a criterion for delisting; the challenge arises when conditions exist in combination--how does one 'sum' up these conditions to quantify risk? Physical frailty, conceptually, represents the conditions in a candidate that are unlikely to reverse after liver function returns, or will take so long to reverse that the patient will be highly vulnerable to postoperative complications. Pretransplant assessments of physical frailty, which are objective, easily administered, and repeated in the clinical setting, enable us to measure the extent to which these factors, in isolation or combination, will reduce both quantity and quality of life after liver transplant. SUMMARY In this article, I introduce a framework that incorporates objective pretransplant assessments of physical frailty to facilitate the decision regarding when a patient is too sick for transplant.
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Bambha KM. Implications of an aging liver transplant waiting list: Survival benefit should be based upon "mile-age" and performance. Liver Transpl 2015; 21:1459-61. [PMID: 26476094 DOI: 10.1002/lt.24357] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2015] [Accepted: 10/15/2015] [Indexed: 02/07/2023]
Affiliation(s)
- Kiran M Bambha
- Division of Gastroenterology and Hepatology, Anschutz Medical Campus, University of Colorado, Denver, Aurora, CO
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