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Pahari H, Tripathi S, Nundy S. Frailty as a determinant of liver transplant outcomes: A call for integrative strategies. World J Transplant 2025; 15:104500. [DOI: 10.5500/wjt.v15.i3.104500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Revised: 03/09/2025] [Accepted: 03/20/2025] [Indexed: 04/18/2025] Open
Abstract
Frailty has emerged as a pivotal determinant of post-liver transplant (LT) outcomes, yet its integration into clinical practice remains inconsistent. Defined by functional impairments and reduced physiologic reserve, frailty transcends traditional metrics like the model for end-stage liver disease (MELD) score, demonstrating increasing predictive value for mortality beyond the immediate post-operative period. Recent findings suggest that frail recipients experience significantly higher mortality within the first 12 months following transplantation—a period when traditional monitoring often wanes. This raises critical questions about the adequacy of current assessment and follow-up protocols. The observed dissociation between MELD scores and long-term survival underscores the limitations of existing selection criteria. Frailty, as a dynamic and modifiable condition, represents an opportunity for targeted intervention. Prehabilitation programs focusing on nutritional optimization, physical rehabilitation, and psychosocial support could enhance resilience in transplant candidates, reducing their risk profile and improving post-transplant outcomes. Furthermore, these findings call for an expanded approach to post-transplant monitoring. Extending surveillance for frail recipients beyond standard timelines may facilitate early detection of complications, mitigating their impact on survival. Incorporating frailty into both pre- and post-transplant protocols could redefine how transplant centers evaluate and manage risk. This editorial advocates for a paradigm shift: Frailty must no longer be viewed as a secondary consideration but as a core element in LT care. By addressing frailty comprehensively, we can move toward more personalized, effective strategies that improve survival and quality of life for LT recipients.
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Affiliation(s)
- Hirak Pahari
- Department of Liver Transplant and Hepatobiliary Surgery, Sir Ganga Ram Hospital, New Delhi 110060, India
| | - Shikhar Tripathi
- Department of Surgical Gastroenterology and Liver Transplant, Sir Ganga Ram Hospital, New Delhi 110060, India
| | - Samiran Nundy
- Department of Surgical Gastroenterology and Liver Transplant, Sir Ganga Ram Hospital, New Delhi 110060, India
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Balogh J, Mubashir T, Li Y, Digbeu BD, Hegde N, Pour FM, Rezapour M, Lai HY, West K, Chaudhry RA, Williams GW, Maroufy V. Effect of frailty as measured by functional impairment on long-term outcomes in liver transplantation in the United States. World J Transplant 2025; 15:98228. [DOI: 10.5500/wjt.v15.i2.98228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 10/08/2024] [Accepted: 12/09/2024] [Indexed: 02/21/2025] Open
Abstract
BACKGROUND In patients with chronic liver disease or hepatic dysfunction with sarcopenia, there is an increased risk of frailty as measured by functional impairment, making frailty a vital predictor of post-transplant mortality.
AIM To investigate the effects of frailty on mortality after liver transplantation.
METHODS A retrospective review of post-transplant outcomes in liver transplant recipients assessed frailty using Karnofsky Performance Score. Data from the Scientific Registry of Transplant Recipients database for 37427 liver transplant recipients was used.
RESULTS Of 82.7% frail patients, 42.7% were severely frail and 40% were moderately frail (P < 0.001) at the time of transplantation. Compared with non-frail patients, post-transplant mortality in frail patients was significantly higher at 12 months [odds ratio (OR) = 1.94, P = 0.02)]. Secondary analysis of the data revealed that liver grafts from donation after circulatory death (DCD) were more likely to be associated with frail patients at transplant (OR = 1.86, P < 0.001). Furthermore, a donor history of hypertension was associated with a lower likelihood of frailty in the recipient at the time of transplant (OR = 0.65, P = 0.03).
CONCLUSION Recipient frailty is associated with increased mortality at 12 months following liver transplantation, and liver transplants from donors with DCD are associated with increased frailty of the liver transplant recipient.
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Affiliation(s)
- Julius Balogh
- Department of CV Anesthesia, CHI St. Vincent Infirmary, Little Rock, AR 72205, United States
| | - Talha Mubashir
- Department of CV Anesthesia, CHI St. Vincent Infirmary, Little Rock, AR 72205, United States
| | - Yuan Li
- Department of Biostatistics and Data Science, The University of Texas Health Center at Houston School of Public Health, Houston, TX 77030, United States
| | - Biai D Digbeu
- Department of Biostatistics and Data Science, The University of Texas Health Center at Houston School of Public Health, Houston, TX 77030, United States
| | - Nikita Hegde
- Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98195, United States
| | - Fatemeh Movaghari Pour
- Department of Comprehensive Dentistry, UT Health San Antonio School of Dentistry, San Antonio, TX 78229, United States
| | | | - Hong-Yin Lai
- Department of Biostatistics and Data Science, The University of Texas Health Center at Houston School of Public Health, Houston, TX 77030, United States
| | - Kelly West
- Department of Anesthesiology, Critical Care and Pain Medicine, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX 77030, United States
| | - Rabail A Chaudhry
- Department of Anesthesiology and Pain Medicine, University of Arizona College of Medicine-Tucson, Tucson, AZ 85724, United States
| | - George W Williams
- Department of Anesthesiology, Critical Care and Pain Medicine, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX 77030, United States
| | - Vahed Maroufy
- Department of Biostatistics and Data Science, The University of Texas Health Center at Houston School of Public Health, Houston, TX 77030, United States
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Miller TM, Russell CL. An Integrative Review of Frailty, Patient Mortality and Graft Failure in Solid Organ Transplant. Prog Transplant 2025:15269248251343387. [PMID: 40388942 DOI: 10.1177/15269248251343387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/21/2025]
Abstract
IntroductionCharacteristics and the impact of frailty on adult solid organ transplant recipients have not been clearly described. The purpose of this integrative review was to identify characteristics of frailty and associations between frailty and patient mortality and graft failure in adult solid organ transplant recipients.MethodsAn integrative literature review was performed using Cooper's integrative methodology. PubMed, Excerpta Medica, and the Cumulative Index of Nursing and Allied Health Literature databases were searched using the terms frailty and transplant. Inclusion criteria were primary research reports, written in English, focusing on adult solid organ transplant recipients, and including graft or patient survival outcomes.ResultsThe review included 35 articles, were largely retrospective, and published between 2015 and 2023 in 11 different countries. Most studies were single-center studies that were not theory-based, and liver transplant recipients were highly represented. Males outnumbered females in the majority of studies and White race was represented in half of the studies. Most studies used one strategy to measure frailty, and modified versions of the Physical Frailty Phenotype were the measurement used most often. Of the 35 articles that investigated the association of frailty with patient mortality, 44 measures were used, and of those, 32 showed a significant association. For graft failure, of the 10 studies included, half showed a significant association between frailty and graft failure.ConclusionThis integrative review offers insights into the characteristics and the association between frailty, patient mortality, and graft failure.
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Affiliation(s)
- Theresa M Miller
- School of Nursing and Health Sciences, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Cynthia L Russell
- School of Nursing and Health Sciences, University of Missouri-Kansas City, Kansas City, MO, USA
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Alqahtani SA, Shpoliansky M, Vandriel SM, Johara F, Quammie C, Lurz E, Alonso EM, Daniel JF, Venkat VL, Leung DH, Economides J, Hsu EK, Loomes KM, Gupta NA, Mannino D, Menendez J, Ng VL, Kamath BM. Frailty in Pediatric Liver Disease May Be Associated With an Increased Incidence of Readmissions After Pediatric Liver Transplantation. Pediatr Transplant 2025; 29:e70077. [PMID: 40230032 DOI: 10.1111/petr.70077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 03/24/2025] [Accepted: 03/27/2025] [Indexed: 04/16/2025]
Abstract
BACKGROUND Frailty is a phenotype of cumulative decline leading to decreased physiologic reserve and vulnerability to stressors. Frailty is associated with adverse outcomes after liver transplantation (LT) in adults, but similar data are not available in children. A prospective multicenter study previously determined that frailty is present in 46% of children with end-stage liver disease (ESLD). We utilized this cohort to evaluate the impact of pre-transplant frailty on post-LT outcomes. METHODS The study included pediatric participants from the original frailty study across 10 North American transplant centers who had subsequently undergone LT. Clinical outcomes were collected up to 1 year post LT. Participants were stratified by their pre-transplant frailty score (defined by a pre-LT frailty score of ≥ 6.0) and long-term outcomes were compared between groups. RESULTS 28 (60.7% female, 46.4% biliary atresia) pediatric LT recipients were included, and 54% of children met criteria for frailty (n = 15). Baseline characteristics were comparable between groups; however, those with frailty were significantly more likely to have pre-transplant failure to thrive (33.3% vs. 0%, p = 0.044). Thirty-four hospital readmissions (22 in frail and 12 in non-frail children) occurred in 20 patients. Higher pre-transplant frailty scores were also significantly associated with an increased number of readmissions after transplantation (p = 0.034). CONCLUSIONS Pediatric frailty may be associated with the adverse outcome of increased frequency of hospitalization in the first year after pediatric liver transplantation. These data support the concept that frail children should be identified and targeted for prehabilitation prior to LT.
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Affiliation(s)
- Saleh A Alqahtani
- Department of Pediatrics, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Michael Shpoliansky
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- University of Toronto, Toronto, Ontario, Canada
- Health Sciences Centre, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Shannon M Vandriel
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- University of Toronto, Toronto, Ontario, Canada
| | - Fatema Johara
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- University of Toronto, Toronto, Ontario, Canada
| | - Claudia Quammie
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- University of Toronto, Toronto, Ontario, Canada
| | - Eberhard Lurz
- Department of Pediatrics, Division of Gastroenterology and Hepatology, Dr. von Hauner Children's Hospital, University Hospital, LMU, Munich, Germany
| | - Estella M Alonso
- Division of Gastroenterology, Hepatology and Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA
| | - James F Daniel
- Division of Pediatric Gastroenterology, Children's Mercy Hospital, Kansas City, Missouri, USA
| | - Veena L Venkat
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Daniel H Leung
- Division of Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Houston, Texas, USA
| | - Julie Economides
- Division of Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Houston, Texas, USA
| | - Evelyn K Hsu
- Division of Gastroenterology and Hepatology, University of Washington-Seattle Children's Hospital, Seattle, Washington, USA
| | - Kathleen M Loomes
- Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Nitika A Gupta
- Division of Gastroenterology, Hepatology and Nutrition, Children's Healthcare of Atlanta Emory University School of Medicine, Atlanta, Georgia, USA
| | - Dana Mannino
- Division of Solid Organ Transplantation, Nemours Children's Hospital, Wilmington, Delaware, USA
| | - Jerome Menendez
- Division of Pediatric Gastroenterology, Levine Children's Hospital Carolinas Health Care Center, Charlotte, North Carolina, USA
| | - Vicky L Ng
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- University of Toronto, Toronto, Ontario, Canada
- Transplant and Regenerative Medicine Centre, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Binita M Kamath
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Kochar B, Cheng D, Lehto HR, Jain N, Araka E, Ritchie CS, Bernacki R, Orkaby AR. Application of an Electronic Frailty Index to Identify High-Risk Older Adults Using Electronic Health Record Data. J Am Geriatr Soc 2025; 73:1491-1497. [PMID: 39982448 PMCID: PMC12101934 DOI: 10.1111/jgs.19389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 01/13/2025] [Accepted: 01/19/2025] [Indexed: 02/22/2025]
Abstract
BACKGROUND Measurement of frailty is limited in clinical practice. Existing electronic frailty indices (eFIs) are derived from routine primary care encounters, with near-complete health condition capture. We aimed to develop an eFI from routinely collected clinical data and evaluate its performance in older adults without complete health condition capture. METHODS Using Electronic Health Record (EHR) data from an integrated regional health system, we created a cohort of patients who were ≥ 60 years on January 1, 2017 with two outpatient encounters in 3 years prior or one outpatient encounter in 2 years prior. We developed an eFI based on 31 age-related deficits identified using diagnostic and procedure codes. Frailty status was categorized as robust (eFI < 0.1), prefrail (0.1-0.2), frail (0.2-0.3), and very frail (> 0.3). We estimated cumulative incidence of mortality, acute care visits and readmissions by frailty, and fit Cox proportional hazards models. We repeated analyses in a sub-cohort of patients who receive primary care in the system. RESULTS Among 518,449 patients, 43% were male with a mean age of 72 years; 73% were robust, 16% were pre-frail, 7% were frail, and 4% were very frail. Very frail older adults had a significantly higher risk for mortality (HR: 4.1, 95% CI: 4.0-4.3), acute care visits (HR: 5.5, 95% CI: 5.4-5.6), and 90-day readmissions (HR: 2.1, 95% CI: 2.1-2.2) than robust older adults. In a primary care sub-cohort, while prevalence of deficits was higher, associations with outcomes were similar. CONCLUSIONS This eFI identified older adults at increased risk for adverse health outcomes even when data from routine primary care visits were not available. This tool can be integrated into EHRs for frailty assessment at scale.
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Affiliation(s)
- Bharati Kochar
- Gastroenterology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
- The Mongan Institute Center for Aging and Serious Illness, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - David Cheng
- The Mongan Institute Center for Aging and Serious Illness, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
- Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts, USA
| | | | - Nelia Jain
- Dana Farber Cancer Institute, Boston, Massachusetts, USA
| | - Elizabeth Araka
- Gastroenterology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Christine S Ritchie
- The Mongan Institute Center for Aging and Serious Illness, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
- Division of Palliative Care & Geriatric Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Rachelle Bernacki
- Harvard Medical School, Boston, Massachusetts, USA
- Dana Farber Cancer Institute, Boston, Massachusetts, USA
| | - Ariela R Orkaby
- Harvard Medical School, Boston, Massachusetts, USA
- New England Geriatric Research, Education, and Clinical Center (GRECC), VA Boston Healthcare System, Boston, Massachusetts, USA
- Division of Aging, Brigham & Women's Hospital, Boston, Massachusetts, USA
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Sogbe M, Hummer B, Stine JG, Lizaola-Mayo B, Forman DE, Vargas HE, Duarte-Rojo A. Advanced Liver Fibrosis Impairs Cardiorespiratory Fitness in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease. Dig Dis Sci 2025; 70:1530-1539. [PMID: 39966289 DOI: 10.1007/s10620-025-08893-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Accepted: 01/25/2025] [Indexed: 02/20/2025]
Abstract
BACKGROUND MASLD is a leading reason for liver transplant waitlisting. The relationship between cardiorespiratory fitness (CRF) and liver fibrosis in patients with MASLD remains unclear. This study aims to provide further evidence supporting the relationship between liver fibrosis and CRF. METHODS Participants with MASLD across various fibrosis stages, including those with cirrhosis awaiting liver transplantation from three U.S. transplant centers, underwent cardiopulmonary exercise testing (CPX). We compared participants based on fibrosis stage (F0-F1, F2-F3, and F4) and CPX parameters such as VO2peak, respiratory exchange ratio (RER), ventilatory efficiency (VE/VCO2), double product (DP) and chronotropic incompetence (CI). Multivariable models were then built to evaluate factors associated with these parameters. RESULTS Sixty-one participants underwent CPX testing across three centers. Participants with F4 had lower VO2peak (11.8 mL/kg/min) compared to F0-F1 (22.2 mL/kg/min) and F2-F3 (22.9 mL/kg/min), p < 0.001. Participants with F4 had higher RER (median 1.25) compared to F0-F1 (1.08) and F2-F3 (1.05), p = 0.001. Similarly, F4 participants exhibited higher VE/VCO2 (median 36.5) compared to F0-F1 (31) and F2-F3 (30), p < 0.001. Additionally, F4 participants had lower DP values (median 17,696) compared to F0-F1 (25,460) and F2-F3 (25,372), and higher prevalence of CI (90%) compared to F0-F1 (39%) and F2-F3 (25%), both p = < 0.001. Multivariable modeling confirmed advanced fibrosis (F > 3) as an independent predictor of low CRF. CONCLUSIONS In MASLD patients, advanced liver fibrosis, particularly cirrhosis, is associated with reduced CRF and poorer hemodynamic performance during CPX. Prioritizing exercise training for those in earlier stages (F3) may prevent fitness decline, which could hinder physical training and liver transplantation candidacy.
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Affiliation(s)
- Miguel Sogbe
- Liver Unit, Clinica Universidad de Navarra, Pamplona, Spain
| | - Breianna Hummer
- Division of Gastroenterology & Hepatology, Department of Medicine, The Pennsylvania State University - Milton S. Hershey Medical Center, Hershey, PA, USA
| | - Jonathan G Stine
- Division of Gastroenterology & Hepatology, Department of Medicine, The Pennsylvania State University - Milton S. Hershey Medical Center, Hershey, PA, USA
- Department of Public Health Sciences, The Pennsylvania State University - Milton S. Hershey Medical Center, Hershey, PA, USA
- Cancer Institute, The Pennsylvania State University - Milton S. Hershey Medical Center, Hershey, PA, USA
- Liver Center, The Pennsylvania State University - Milton S. Hershey Medical Center, Hershey, PA, USA
| | - Blanca Lizaola-Mayo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Phoenix, AZ, USA
| | - Daniel E Forman
- Divisions of Cardiology and Geriatrics, Department of Medicine, University of Pittsburgh, and the Pittsburgh Geriatrics, Research, Education and Clinical Center (GRECC), VA Pittsburgh Healthcare System, Pittsburgh, PA, USA
| | - Hugo E Vargas
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Phoenix, AZ, USA
| | - Andres Duarte-Rojo
- Division of Gastroenterology and Hepatology, Department of Medicine, Comprehensive Transplant Center, Northwestern Medicine, Feinberg School of Medicine, Northwestern University, 676 N. St. Clair St., Room 1900, Chicago, IL, USA.
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McMillan JM, Falutz J. Is Frailty the Geriatric Troponin? J Am Geriatr Soc 2025; 73:999-1001. [PMID: 40072284 DOI: 10.1111/jgs.19423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Accepted: 02/11/2025] [Indexed: 04/05/2025]
Affiliation(s)
| | - Julian Falutz
- McGill University Health Centre, McGill University, Montreal, Canada
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Wang M, Chiou SH, Ganger D, Ruck J, Huang CY, Kappus MR, King EA, Ladner DP, Rahimi RS, Duarte-Rojo A, Volk ML, Tevar AD, Verna EC, Lai JC. Liver transplantation provides survival benefit at all levels of frailty: From the Multicenter Functional Assessment in Liver Transplantation Study. Hepatology 2025; 81:1269-1275. [PMID: 39047086 PMCID: PMC11757801 DOI: 10.1097/hep.0000000000001030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Accepted: 07/05/2024] [Indexed: 07/27/2024]
Abstract
BACKGROUND AND AIMS Offering LT to frail patients may reduce waitlist mortality but may increase post-LT mortality. LT survival benefit is the concept of balancing these risks. We sought to quantify the net survival benefit with LT by liver frailty index (LFI). APPROACH AND RESULTS We analyzed data in the multicenter Functional Assessment in LT (FrAILT) study from 2012 to 2021. Pre-LT cohort included ambulatory patients with cirrhosis awaiting LT, without HCC; the post-LT cohort included those who underwent LT. Primary outcomes were pre-LT and post-LT mortality. We computed 1-, 3-, and 5-year restricted mean survival times (RMSTs) from adjusted Cox models. The survival benefit was calculated as a net gain in life-years with LT. Pre-LT cohort included 2628 patients: median Model for End-Stage Liver Disease-Sodium was 18 (IQR: 14-22); 731 (28%) were frail; 440 (17%) died before LT. Post-LT cohort included 1335 patients: median Model for End-Stage Liver Disease-Sodium was 20 (IQR: 14-24); 325 (24%) were frail; 103 (8%) died after LT. Pre-LT RMST decreased substantially as LFI increased. Post-LT RMST also decreased as LFI increased but only modestly. There was no LFI threshold at which pre-LT and post-LT RMST intersected-patients had net survival benefits at all LFI values. CONCLUSIONS Pre-LT and, to a lesser degree, post-LT mortality increased as LFI increased. Transplant offered a survival benefit at all LFI values, driven by a reduction in pre-LT mortality. No threshold of LFI was identified at which the risk of post-LT mortality exceeded pre-LT mortality. LT offers net survival benefits even in the presence of advanced frailty among those selected for LT.
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Affiliation(s)
- Melinda Wang
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California San Francisco, San Francisco, California, USA
| | - Sy Han Chiou
- Department of Statistics and Data Science, Southern Methodist University, Dallas, Texas, USA
| | - Daniel Ganger
- Northwestern University Transplant Outcomes Transplant Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern Medicine, Chicago, Illinois, USA
| | - Jessica Ruck
- Department of Surgery, John Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Chiung-Yu Huang
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA
| | - Matthew R. Kappus
- Department of Medicine, Division of Gastroenterology and Hepatology, Duke University School of Medicine, Durham, North Carolina, USA
| | - Elizabeth A. King
- Department of Surgery, John Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Daniela P. Ladner
- Northwestern University Transplant Outcomes Transplant Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern Medicine, Chicago, Illinois, USA
| | - Robert S. Rahimi
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Baylor Scott and White Health, Dallas, Texas, USA
| | - Andres Duarte-Rojo
- Northwestern University Transplant Outcomes Transplant Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern Medicine, Chicago, Illinois, USA
| | - Michael L. Volk
- Department of Medicine, Division of Gastroenterology and Hepatology, Loma Linda University Health, Loma Linda, California, USA
| | - Amit D. Tevar
- Department of Surgery and Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Elizabeth C. Verna
- Center for Liver Disease and Transplantation, Columbia University Irving Medical Center, New York, New York, USA
| | - Jennifer C. Lai
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California San Francisco, San Francisco, California, USA
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Lai JC, Shui AM, Molinari M, Rahimi RS, Ladner DP, Ganger DR, Kappus M, King EA, Tevar AD, Volk ML, Duarte-Rojo A, Verna EC. The Liver Transplant Comorbidity Index (LTCI): A composite index of ambulatory pre-LT factors to identify patients at increased risk of post-LT mortality. Hepatology 2025:01515467-990000000-01217. [PMID: 40132167 DOI: 10.1097/hep.0000000000001320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Accepted: 03/10/2025] [Indexed: 03/27/2025]
Abstract
BACKGROUND AND AIMS Frailty is strongly associated with mortality after liver transplantation. However, national guidelines discourage its use as a sole reason to decline a patient for liver transplantation, as some frail patients have acceptable outcomes. We aimed to develop a composite index, the Liver Transplant Comorbidity Index (LTCI), integrating frailty and other comorbidities, as a risk factor for longer-term (3-year) posttransplant mortality. APPROACH AND RESULTS This 8-center prospective Functional Assessment in Liver Transplantation (FrAILT) Study included adult recipients of a primary deceased donor liver transplant from 2012 to 2022. Frailty was measured using the Liver Frailty Index (LFI ≥4.5=frail). Other candidate variables included demographics, laboratories, and comorbidities. Cox proportional hazards regression with best subset selection was used to identify risk factors of 3-year posttransplant death. The final model was selected based on Akaike Information Criterion and clinical pragmatism. Of 1472 liver transplant recipients, 290 (20%) were frail. Three-year posttransplant mortality was higher in frail versus non-frail patients (13% vs. 8%; p =0.03). The final LTCI included 5 variables: frailty, coronary artery disease, HCC, renal dysfunction, and diabetes. Three-year posttransplant mortality in low-risk, moderate-risk, and high-risk LTCI groups was 93%, 87%, and 80%, respectively. In multivariable analysis, after adjusting for donor factors (age and donation after circulatory death), both moderate-risk (HR: 2.23, 95% CI: 1.46-3.40; p <0.001) and high-risk (HR: 2.78, 95% CI: 1.67-4.64; p <0.001) status were associated with 3-year posttransplant mortality. CONCLUSIONS The LTCI, comprising 5 pretransplant clinical parameters, effectively identifies patients at increased risk of posttransplant mortality. By integrating frailty in the context of other comorbidities, the LTCI can help providers better weigh the relative transplant risks and benefits and standardize the selection of transplant candidates.
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Affiliation(s)
- Jennifer C Lai
- Department of Medicine, University of California, San Francisco, USA
| | - Amy M Shui
- Department of Medicine, University of California, San Francisco, USA
| | - Michele Molinari
- Department of Surgery and Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Robert S Rahimi
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Baylor Scott and White Health, Dallas, TX, USA
| | - Daniela P Ladner
- Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Daniel R Ganger
- Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Matthew Kappus
- Department of Medicine, Duke University School of Medicine, Durham, NC, USA
| | - Elizabeth A King
- Department of Surgery, Johns Hopkins Medical Institute, Baltimore, MD, USA
| | - Amit D Tevar
- Department of Surgery and Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Michael L Volk
- Department of Medicine, Baylor Scott & White Health, Dallas, TX, USA
| | | | - Elizabeth C Verna
- Center for Liver Disease and Transplantation, Columbia University Medical Center, New York, NY, USA
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10
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Orbuch R, Bloomer PM, Sejdic E, Li W, Duarte-Rojo A. Processing Mobility Data Through Artificial Intelligence Can Identify Patterns of Physical Activity in Liver Transplant Candidates. Clin Gastroenterol Hepatol 2025:S1542-3565(25)00194-6. [PMID: 40089254 DOI: 10.1016/j.cgh.2025.01.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 12/29/2024] [Accepted: 01/07/2025] [Indexed: 03/17/2025]
Affiliation(s)
- Rachel Orbuch
- Division of General Internal Medicine, Department of Medicine, McGaw Medical Center of Northwestern University, Chicago, Illinois
| | - Pamela M Bloomer
- Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Ervin Sejdic
- Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario, Canada
| | - Wuqi Li
- Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario, Canada
| | - Andres Duarte-Rojo
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University, Chicago, Illinois
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11
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Tapper EB, Nikirk S, Evon DM, Asrani S, Bloom P, Hynes JW, Alber JM, Gill A, Mehta S, Weinberg E, Alexander NB, Althuis K, Hoelscher A, Zhao L, Chen X, Burdzy A, Serper M. LIVE-SMART: A sequential, multiple assignment randomized trial to reduce falls in cirrhosis. Hepatol Commun 2025; 9:e0626. [PMID: 39969429 PMCID: PMC11841856 DOI: 10.1097/hc9.0000000000000626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 11/04/2024] [Indexed: 02/20/2025] Open
Abstract
INTRODUCTION Falls are a major threat to the well-being of patients with cirrhosis. We are performing a clinical trial to determine whether lactulose, TeleTai-Chi, or their combination will reduce falls in HE and improve health-related quality of life (HRQOL) among patients with cirrhosis. METHODS AND ANALYSIS Patients with cirrhosis and portal hypertension without HE will be enrolled in 3 US states and followed participants for 24 weeks. In stage 1 (12 wk), participants will be randomized to receive either lactulose therapy or enhanced usual care. In stage 2 (12 wk), participants will be randomized to either TeleTai-Chi or usual care. The primary outcome is a hierarchical composite: Injurious falls, noninjurious falls, incident HE, and death/transplantation. Secondary outcomes include cognitive function, days-alive and out-of-hospital, and HRQOL. After completion of the interventions, participants will be followed for 48 weeks for health and financial outcomes. ETHICS AND DISSEMINATION Our study has a central institutional review board with individual site IRB review. Dissemination includes the publication of study findings and patient-focused educational webinars.
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Affiliation(s)
- Elliot B. Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, USA
| | - Samantha Nikirk
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, USA
| | - Donna M. Evon
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, USA
| | - Sumeet Asrani
- Baylor University Medical Center, Dallas, Texas, USA
| | - Patricia Bloom
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, USA
| | | | - J. Mark Alber
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, USA
| | - Anna Gill
- Baylor University Medical Center, Dallas, Texas, USA
| | | | | | - Neil B. Alexander
- Department of Veterans Affairs, Geriatric Research Education Clinical Center, Ann Arbor, USA
| | - Katie Althuis
- Department of Veterans Affairs, Geriatric Research Education Clinical Center, Ann Arbor, USA
| | - Alise Hoelscher
- Department of Veterans Affairs, Geriatric Research Education Clinical Center, Ann Arbor, USA
| | - Lili Zhao
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, USA
| | - Xi Chen
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, USA
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12
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Liu Z, Xu J, Que T, Que S, Valenti L, Zheng S. Molecular Mechanisms of Ischemia/Reperfusion Injury and Graft Dysfunction in Liver Transplantation: Insights from Multi-Omics Studies in Rodent Animal Models. Int J Biol Sci 2025; 21:2135-2154. [PMID: 40083684 PMCID: PMC11900806 DOI: 10.7150/ijbs.109449] [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: 12/26/2024] [Accepted: 01/25/2025] [Indexed: 03/16/2025] Open
Abstract
Rodent ischemia-reperfusion injury (IRI) and liver transplantation (LT) models play crucial roles in mimicking graft injury and immune rejection, developing therapeutic approaches, and evaluating the efficacy of treatments. The application of integrated multi-omics data and advanced omics techniques like single-cell RNA sequencing in rodent models has expanded researchers' perspectives on pathophysiological processes in LT settings. This review summarizes key molecules and pathways associated with reperfusion injury and prognosis in LT models, highlighting the potential of omics data in understanding and improving transplant outcomes. In addition, we highlight the current challenges and future approaches for the application of omics data in rodent LT models. Cross-species validation with human data will improve therapeutic potential. Finally, further applications combining advanced single-cell, spatial omics technologies and machine learning algorithms will help to identify the key regulatory networks in specific cell populations underlying poor outcomes after LT.
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Affiliation(s)
- Zhengtao Liu
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Shulan Hospital (Hangzhou), Hangzhou, China
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Organ Transplantation, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Jun Xu
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Organ Transplantation, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Ting Que
- Birth Defects Prevention and Control Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
| | | | - Luca Valenti
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
- Precision Medicine, Biological Resource Center Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Shusen Zheng
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Shulan Hospital (Hangzhou), Hangzhou, China
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Organ Transplantation, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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13
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Fadlallah H, El Masri D, Bahmad HF, Abou-Kheir W, El Masri J. Update on the Complications and Management of Liver Cirrhosis. Med Sci (Basel) 2025; 13:13. [PMID: 39982238 PMCID: PMC11843904 DOI: 10.3390/medsci13010013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2025] [Revised: 02/01/2025] [Accepted: 02/02/2025] [Indexed: 02/22/2025] Open
Abstract
Liver cirrhosis represents the advanced pathological stage of chronic liver disease, characterized by the progressive destruction and regeneration of the hepatic parenchyma over years, culminating in fibrosis and disruption of the vascular architecture. As a leading global cause of morbidity and mortality, it continues to affect millions worldwide, imposing a substantial burden on healthcare systems. Alcoholic/nonalcoholic fatty liver disease and chronic viral hepatitis infection, hepatitis C (HCV) in particular, remain leading causes of cirrhosis. Despite significant advances in understanding the pathogenesis of cirrhosis, its management is still complex due to the multifaceted complications, including ascites, hepatic encephalopathy, variceal bleeding, and hepatocellular carcinoma, all of which severely compromise the patient outcomes and quality of life. This review aims at filling a critical gap by providing a comprehensive summary of the latest evidence on the complications and management of liver cirrhosis. Evidence-based therapies targeting both the etiologies and complications of cirrhosis are essential for improving outcomes. While liver transplantation is considered a definitive cure, advancements in pharmacological therapies offer promising avenues for halting and potentially reversing disease progression. This review summarizes the latest management strategies for cirrhosis and its associated complications, emphasizing the importance of early intervention and novel therapeutic options for improving outcomes and quality of life in affected individuals.
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Affiliation(s)
- Hiba Fadlallah
- Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon; (H.F.); (J.E.M.)
| | - Diala El Masri
- Faculty of Medicine, University of Balamand, Al-Kurah, Tripoli P.O. Box 100, Lebanon;
| | - Hisham F. Bahmad
- Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA;
| | - Wassim Abou-Kheir
- Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon; (H.F.); (J.E.M.)
| | - Jad El Masri
- Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon; (H.F.); (J.E.M.)
- Faculty of Medical Sciences, Lebanese University, Beirut 1107-2020, Lebanon
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14
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Miller WC, Yousefzadeh MJ, Fisher J, Sarumi H, Kirchner V, Niedernhofer LJ, Pruett T. A brief report on biomarkers of cellular senescence associated with liver frailty and length of stay in liver transplantation. GeroScience 2024:10.1007/s11357-024-01482-9. [PMID: 39739255 DOI: 10.1007/s11357-024-01482-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 12/14/2024] [Indexed: 01/02/2025] Open
Abstract
The proportion of older individuals needing liver transplantation is growing, resulting in an increasingly frail patient population. Frailty constitutes a constellation of cognitive and physical symptoms associated with aging and increases the risk of morbidity and mortality. Senescence is a programmed cell fate in response to stress implicated in causing frailty, age-related diseases, and aging itself. This study explores the relationship between cellular senescence, physical frailty, and liver transplantation. Adults > 18 years old who underwent ambulatory liver transplantation at our center between September 1, 2022, and November 30, 2022, were included. Frailty assessments were performed using the Liver Frailty Index™, and blood was collected prior to transplantation. Expression of p16INK4a and p21CIP1 mRNA in T cells was measured by RT-qPCR, an established proxy for senescent cell burden, and plasma levels of senescence-associated secretory phenotype proteins were measured by multiplex ELISA. Patient outcomes were collected via electronic medical record. Univariate linear regression analysis demonstrated a statistically significant relationship between baseline patient frailty and p16INK4a and p21CIP1 (r2 = 0.5092, p-value = 0.0205; r2 = 0.5339, p-value = 0.0164, respectively). A similar correlation occurred between p16INK4a and p21CIP1 expression and length of hospitalization (r2 = 0.4960, p-value = 0.0230; r2 = 0.5868, p-value = 0.0098, respectively). This study revealed a potential association between biomarkers of cellular senescence, physical frailty, and length of hospitalization. This warrants further investigation as biomarkers to stratify patients are needed and therapeutics to reduce senescent cell burden exists and could be deployed to improve transplant outcomes.
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Affiliation(s)
- William C Miller
- University of Minnesota Medical School, Minneapolis, MN, USA
- Division of Solid Organ Transplantation, Department of Surgery, University of Minnesota, 420 Delaware St SE, Minneapolis, MN, 55455, USA
| | - Matthew J Yousefzadeh
- Department of Medicine, Columbia Center for Translational Immunology, Columbia Center for Human Longevity, Columbia University Medical Center, New York, NY, USA
- Institute On the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA
- Department of Biochemistry, Molecular Biology and Biophysics, College of Biological Sciences, University of Minnesota, Minneapolis, MN, USA
| | - Jessica Fisher
- Division of Solid Organ Transplantation, Department of Surgery, University of Minnesota, 420 Delaware St SE, Minneapolis, MN, 55455, USA
| | - Heidi Sarumi
- Division of Solid Organ Transplantation, Department of Surgery, University of Minnesota, 420 Delaware St SE, Minneapolis, MN, 55455, USA
| | - Varvara Kirchner
- Institute On the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA
- Division of Abdominal Transplantation, Department of Surgery, Palo Alto, CA, USA
| | - Laura J Niedernhofer
- Institute On the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA
- Department of Biochemistry, Molecular Biology and Biophysics, College of Biological Sciences, University of Minnesota, Minneapolis, MN, USA
| | - Timothy Pruett
- Division of Solid Organ Transplantation, Department of Surgery, University of Minnesota, 420 Delaware St SE, Minneapolis, MN, 55455, USA.
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15
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Samuel D, De Martin E, Berg T, Berenguer M, Burra P, Fondevila C, Heimbach JK, Pageaux GP, Sanchez-Fueyo A, Toso C. EASL Clinical Practice Guidelines on liver transplantation. J Hepatol 2024; 81:1040-1086. [PMID: 39487043 DOI: 10.1016/j.jhep.2024.07.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 07/30/2024] [Indexed: 11/04/2024]
Abstract
Liver transplantation (LT) is an established life-saving procedure. The field of LT has changed in the past 10 years from several perspectives, with the expansion of indications, transplantation of patients with acute-on-chronic liver failure, evolution of transplant oncology, the use of donations after cardiac death, new surgical techniques, and prioritisation of recipients on the waiting list. In addition, the advent of organ perfusion machines, the recognition of new forms of rejection, and the attention paid to the transition from paediatric to adult patients, have all improved the management of LT recipients. The purpose of the EASL guidelines presented here is not to cover all aspects of LT but to focus on developments since the previous EASL guidelines published in 2016.
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16
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Hughes DL, Lizaola-Mayo B, Wheatley-Guy CM, Vargas HE, Bloomer PM, Wolf C, Carey EJ, Forman DE, Duarte-Rojo A. Cardiorespiratory Fitness From Cardiopulmonary Exercise Testing Is a Comprehensive Risk-stratifying Tool in Liver Transplant Candidates. Transplant Direct 2024; 10:e1725. [PMID: 39563725 PMCID: PMC11576030 DOI: 10.1097/txd.0000000000001725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Accepted: 09/09/2024] [Indexed: 11/21/2024] Open
Abstract
Background Cardiovascular disease and physical decline are prevalent and associated with morbidity/mortality in liver transplant (LT) patients. Cardiopulmonary exercise testing (CPX) provides comprehensive cardiopulmonary and exercise response assessments. We investigated cardiorespiratory fitness (CRF) and cardiac stress generated during CPX in LT candidates. Methods LT candidates at 2 centers underwent CPX. Standard-of-care cardiac stress testing (dobutamine stress echocardiography, DSE) results were recorded. Physical function was assessed with liver frailty index and 6-min walk test. CPX/DSE double products were calculated to quantify cardiac stress. To better study the association of CPX-derived metrics with physical function, the cohort was divided into 2 groups based on 6-min walk test median (372 m). Results Fifty-four participants (62 ± 8 y; 65% men, Model for End-Stage Liver Disease-Na 14 [10-18]) underwent CPX. Peak oxygen consumption was 14.1 mL/kg/min for an anerobic threshold of 10.2 mL/kg/min, with further CRF decline in the lower 6MWT cohort despite lack of liver frailty index-frailty in 90%. DSE was nondiagnostic in 18% versus 4% of CPX (P = 0.058). All CPX were negative for ischemia. A double product of ≥25 000 was observed in 32% of CPX and 11% of DSE (P = 0.020). Respiratory function testing was normal. No patient presented major cardiovascular events at 30 d post-LT. Conclusions CPX provided efficient and effective combined cardiopulmonary risk and frailty assessments of LT candidates in a 1-stop test. The CRF was found to be very low despite preserved physical function or lack of frailty.
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Affiliation(s)
- Dempsey L Hughes
- Division of Gastroenterology and Hepatology, Northwestern University, Chicago, IL
| | | | | | - Hugo E Vargas
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ
| | - Pamela M Bloomer
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA
| | - Cody Wolf
- Department of Medicine, University of Pittsburgh; and the Pittsburgh Geriatric, Research, Education and Clinical Center (GRECC), VA Pittsburgh Healthcare System; Pittsburgh, PA
| | - Elizabeth J Carey
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ
| | - Daniel E Forman
- Department of Medicine, University of Pittsburgh; and the Pittsburgh Geriatric, Research, Education and Clinical Center (GRECC), VA Pittsburgh Healthcare System; Pittsburgh, PA
| | - Andres Duarte-Rojo
- Division of Gastroenterology and Hepatology, Northwestern University, Chicago, IL
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17
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Zhang F, Yan Y, Li B, Ge C. Frailty serves as an adverse predictor for mortality in liver transplant candidates: A systematic review and meta-analysis. Transplant Rev (Orlando) 2024; 38:100884. [PMID: 39396446 DOI: 10.1016/j.trre.2024.100884] [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: 07/15/2024] [Revised: 09/29/2024] [Accepted: 10/02/2024] [Indexed: 10/15/2024]
Abstract
BACKGROUND Physical frailty increases susceptibility to stressors and has been associated with increased mortality among liver transplant candidates. However, evidence about this population's frailty prevalence and mortality is inconsistent and needs to be clarified. This study aimed to quantitatively synthesize the prevalence of frailty and the role of frailty on mortality in liver transplant candidates. METHODS All eligible studies published in Embase, PubMed, Scopus, and Web of Science from inception until March 5, 2024, were included. The pooled prevalence and hazard ratio (HR) corresponding to 95 % confidence intervals (CI) in mortality estimates were conducted. The random-effects model was used for the calculations. RESULTS A total of 17 studies containing 4509 patients with liver transplant waitlist candidates were included. The prevalence of frailty in liver transplant waitlist candidates was 32 % (95 % CI = 25-38; p < 0.01). In this population, frailty was associated with an increased hazard ratio for mortality (8 studies) (HR = 2.49; 95 % CI = 1.77-3.51; p < 0.01). Furthermore, subgroup analysis showed that frailty was associated with a higher mortality in the USA (HR = 4.03; 95 % CI = 1.77-3.51; p < 0.01) compared with the non-USA area (HR = 2.03; 95 % CI = 1.51-2.72; p < 0.01). CONCLUSION Our results suggest that frailty is prevalent in patients awaiting liver transplants, which strongly predicts waitlist mortality among this population. These findings highlight the importance of frailty in the decision of transplantation and in designing studies that consider frailty. Reducing the severity or impact of frailty on this population may improve prognosis.
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Affiliation(s)
- Fei Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of China Medical University, Shenyang 110001, China.
| | - Ying Yan
- Department of Urinary Surgery, Northeast International Hospital, Shenyang, 110623, China
| | - Baifeng Li
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of China Medical University, Shenyang 110001, China
| | - Chunlin Ge
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of China Medical University, Shenyang 110001, China
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18
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Wang M, Shui AM, Ruck J, Huang CY, Verna EC, King EA, Ladner DP, Ganger D, Kappus M, Rahimi R, Tevar AD, Duarte-Rojo A, Lai JC. Clinically relevant cut-points for changes in the Liver Frailty Index are associated with waitlist mortality in patients with cirrhosis. Liver Transpl 2024; 30:991-1001. [PMID: 38900010 PMCID: PMC11792089 DOI: 10.1097/lvt.0000000000000418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Accepted: 04/25/2024] [Indexed: 06/21/2024]
Abstract
Physical frailty is a critical determinant of mortality in patients with cirrhosis and can be objectively measured using the Liver Frailty Index (LFI), which is potentially modifiable. We aimed to identify LFI cut-points associated with waitlist mortality. Ambulatory adults with cirrhosis without HCC awaiting liver transplantation from 9 centers from 2012 to 2021 for ≥3 months with ≥2 pre-liver transplantation LFI assessments were included. The primary explanatory variable was the change in LFI from first to second assessments per 3 months (∆LFI); we evaluated clinically relevant ∆LFI cut-points at 0.1, 0.2, 0.3, and 0.5. The primary outcome was waitlist mortality (death or delisting for being too sick), with transplant considered as a competing event. Among 1029 patients, the median (IQR) age was 58 (51-63) years; 42% were female; and the median lab Model for End-Stage Liver Disease-Sodium at first assessment was 18 (15-22). For each 0.1 improvement in ∆LFI, the risk of overall mortality decreased by 6% (cause-specific hazard ratio: 0.94, 95% CI: 0.92-0.97, p < 0.001). ∆LFI was associated with waitlist mortality at cut-points as low as 0.1 (cause-specific hazard ratio: 0.63, 95% CI: 0.46-0.87) and 0.2 (HR: 0.61, 95% CI: 0.42-0.87). An improvement in LFI per 3 months as small as 0.1 in the pre-liver transplantation period is associated with a clinically meaningful reduction in waitlist mortality. These data provide estimates of the reduction in mortality risk associated with improvements in LFI that can be used to assess the effectiveness of interventions targeting physical frailty in patients with cirrhosis.
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Affiliation(s)
- Melinda Wang
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, California, USA
| | - Amy M. Shui
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA
| | - Jessica Ruck
- Department of Surgery, John Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Chiung-Yu Huang
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA
| | - Elizabeth C. Verna
- Center for Liver Disease and Transplantation, Columbia University Irving Medical Center, New York, New York, USA
| | - Elizabeth A. King
- Department of Surgery, John Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Daniela P. Ladner
- Northwestern University Transplant Outcomes Transplant Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern Medicine, Chicago, Illinois, USA
| | - Daniel Ganger
- Northwestern University Transplant Outcomes Transplant Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern Medicine, Chicago, Illinois, USA
| | - Matthew Kappus
- Division of Gastroenterology and Hepatology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
| | - Robert Rahimi
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Baylor Scott and White Health, Dallas, Texas, USA
| | - Amit D. Tevar
- Department of Surgery and Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Andres Duarte-Rojo
- Northwestern University Transplant Outcomes Transplant Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern Medicine, Chicago, Illinois, USA
| | - Jennifer C. Lai
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, California, USA
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19
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Yang F, Li C, Yang W, He Y, Wu L, Jiang K, Sun C. Development and validation of an explainable machine learning model for predicting multidimensional frailty in hospitalized patients with cirrhosis. Brief Bioinform 2024; 25:bbae491. [PMID: 39358034 PMCID: PMC11446601 DOI: 10.1093/bib/bbae491] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 09/10/2024] [Accepted: 09/17/2024] [Indexed: 10/04/2024] Open
Abstract
We sought to develop and validate a machine learning (ML) model for predicting multidimensional frailty based on clinical and laboratory data. Moreover, an explainable ML model utilizing SHapley Additive exPlanations (SHAP) was constructed. This study enrolled 622 patients hospitalized due to decompensating episodes at a tertiary hospital. The cohort data were randomly divided into training and test sets. External validation was carried out using 131 patients from other tertiary hospitals. The frail phenotype was defined according to a self-reported questionnaire (Frailty Index). The area under the receiver operating characteristics curve was adopted to compare the performance of five ML models. The importance of the features and interpretation of the ML models were determined using the SHAP method. The proportions of cirrhotic patients with nonfrail and frail phenotypes in combined training and test sets were 87.8% and 12.2%, respectively, while they were 88.5% and 11.5% in the external validation dataset. Five ML algorithms were used, and the random forest (RF) model exhibited substantially predictive performance. Regarding the external validation, the RF algorithm outperformed other ML models. Moreover, the SHAP method demonstrated that neutrophil-to-lymphocyte ratio, age, lymphocyte-to-monocyte ratio, ascites, and albumin served as the most important predictors for frailty. At the patient level, the SHAP force plot and decision plot exhibited a clinically meaningful explanation of the RF algorithm. We constructed an ML model (RF) providing accurate prediction of frail phenotype in decompensated cirrhosis. The explainability and generalizability may foster clinicians to understand contributors to this physiologically vulnerable situation and tailor interventions.
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Affiliation(s)
- Fang Yang
- Department of Digestive System, Baodi Clinical College of Tianjin Medical University, No.8 Guangchuan Road, Baodi District, Tianjin 301800, China
| | - Chaoqun Li
- Department of Geriatrics, Tianjin Hexi Hospital, No.43 Qiongzhou Road, Hexi District, Tianjin 300202, China
| | - Wanting Yang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
| | - Yumei He
- Department of Gastroenterology, The Third People's Hospital of Chengdu, Chengdu 610031, Sichuan Province, China
| | - Liping Wu
- Department of Gastroenterology, The Third People's Hospital of Chengdu, Chengdu 610031, Sichuan Province, China
| | - Kui Jiang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
| | - Chao Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
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20
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Pomej K, Masel EK, Kreye G. Palliative care in terminally ill advanced chronic liver disease patients. Wien Klin Wochenschr 2024:10.1007/s00508-024-02436-z. [PMID: 39254776 DOI: 10.1007/s00508-024-02436-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Accepted: 08/16/2024] [Indexed: 09/11/2024]
Abstract
While mortality rates from advanced chronic liver disease (ACLD) are rapidly increasing, patients with an advanced disease stage have a comparable or even higher symptom burden than those with other life-limiting diseases. Although evidence is limited there is increasing recognition of the need to improve care for patients with ACLD; however, there are many limiting factors to providing good palliative care for these patients, including unpredictable disease progression, the misconception of palliative care and end of life care as being equivalent, a lack of confidence in prescribing medication and a lack of time and resources. Health professionals working with these patients need to develop the skills to ensure effective palliative care, while referral to specialized palliative care centers should be reserved for patients with complex needs. Basic palliative care, along with active disease management, is best delivered by the treating hepatologists. This includes discussions about disease progression and advance care planning, alongside the active management of disease complications. Liver disease is closely associated with significant social, psychological, and financial burdens for patients and their caregivers. Strategies to engage the discussion in multidisciplinary teams early in disease progression help to ensure addressing these issues proactively. This review summarizes the evidence on palliative care for patients with ACLD, provides examples of current best practice and offers suggestions on how disease-modifying and palliative care can coexist, to ensure that patients do not miss opportunities for quality of life improving interventions.
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Affiliation(s)
- Katharina Pomej
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Eva Katharina Masel
- Division of Palliative Medicine, Department of Medicine I, Medical University of Vienna, Vienna, Austria
| | - Gudrun Kreye
- Division of Palliative Medicine, Clinical Department of Medicine 2, Krems University Hospital, Karl Landsteiner Private University for Health Sciences, Mitterweg 10, 3500, Krems an der Donau, Austria.
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21
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Jothimani D, Rela M, Kamath PS. Management of Portal Hypertension in the Older Patient. Curr Gastroenterol Rep 2024; 26:231-240. [PMID: 38780678 DOI: 10.1007/s11894-024-00930-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/15/2024] [Indexed: 05/25/2024]
Abstract
PURPOSE OF THIS REVIEW Aging is a process of physiological slowing, reduced regenerative capacity and inability to maintain cellular homeostasis. World Health Organisation declared the commencement of population aging globally, largely attributed to improvement in the healthcare system with early diagnosis and effective clinical management. Liver ages similar to other organs, with reduction in size and blood flow. In this review we aim to evaluate the effect of aging in liver disease. RECENT FINDINGS Aging causes dysregulation of major carbohydrate, fat and protein metabolism in the liver. Age is a major risk factor for liver fibrosis accelerated by sinusoidal endothelial dysfunction and immunological disharmony. Age plays a major role in patients with liver cirrhosis and influence outcomes in patients with portal hypertension. Transient elastography may be an useful tool in the assessment of portal hypertension. Hepatic structural distortion, increased vascular resistance, state of chronic inflammation, associated comorbidities, lack of physiological reserve in the older population may aggravate portal hypertension in patients with liver cirrhosis and may result in pronounced variceal bleed. Cut-offs for other non-invasive markers of fibrosis may differ in the elderly population. Non-selective beta blockers initiated at lower dose followed by escalation are the first line of therapy in elderly patients with cirrhosis and portal hypertension, unless contraindicated. Acute variceal bleed in the elderly cirrhotic patients can be life threatening and may cause rapid exsanguination due to poor reserve and associated comorbidities. Vasoactive drugs may be associated with more adverse reactions. Early endoscopy may be warranted in the elderly patients with acute variceal bleed. Role of TIPS in the elderly cirrhotics discussed. Management of portal hypertension in the older population may pose significant challenges to the treating clinician.
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Affiliation(s)
- Dinesh Jothimani
- Institute of Liver disease and Transplantation, Dr Rela Institute and Medical Centre, Chennai, India.
| | - Mohamed Rela
- Institute of Liver disease and Transplantation, Dr Rela Institute and Medical Centre, Chennai, India
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, 55906, USA
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22
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Porter G, Sakowitz S, Mallick S, Vadlakonda A, Curry J, Ali K, Balian J, Benharash P. Association of Frailty With Clinical and Financial Outcomes Following Liver Transplantation. Clin Transplant 2024; 38:e15438. [PMID: 39189807 DOI: 10.1111/ctr.15438] [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: 04/09/2024] [Revised: 07/15/2024] [Accepted: 08/11/2024] [Indexed: 08/28/2024]
Abstract
INTRODUCTION Frailty, a measure of physiological aging and reserve, has been validated as a prognostic indicator of mortality in patients with cirrhosis. However, large-scale analyses of the independent association of frailty with clinical and financial outcomes following liver transplantation (LT) are lacking. METHODS Adults (≥18 years) undergoing LT were identified in the 2016-2020 National Readmissions Database. Frailty was defined using the binary Johns Hopkins Adjusted Clinical Groups frailty indicator. Multivariable linear and logistic regression models were developed to evaluate the independent association of frailty with in-hospital mortality, perioperative complications, and costs. RESULTS Of an estimated 34 442 patients undergoing LT, 8265 (24%) were frail. After adjustment, frailty was associated with greater odds of mortality (adjusted odds ratio [AOR] 1.80; 95% Confidence Interval [CI]: 1.49-1.18), postoperative length of stay (β + 11 days; 95% CI: +10, +12), and hospitalization costs (+$86 880; 95% CI: +75 660, +98 100), as well as a two-fold increase in relative risk of nonhome discharge (AOR 2.17, 95% CI: 1.90-2.49). CONCLUSIONS Frailty is associated with an increased risk of in-hospital mortality, complications, and resource utilization among LT recipients. As the proportion of frail LT patients continues to rise, our findings underscore the need for novel risk-stratification and individualized care protocols for such vulnerable patients.
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Affiliation(s)
- Giselle Porter
- Cardiovascular Outcomes Research Laboratories (CORELAB), University of California, Los Angeles, California, USA
| | - Sara Sakowitz
- Cardiovascular Outcomes Research Laboratories (CORELAB), University of California, Los Angeles, California, USA
| | - Saad Mallick
- Cardiovascular Outcomes Research Laboratories (CORELAB), University of California, Los Angeles, California, USA
| | - Amulya Vadlakonda
- Cardiovascular Outcomes Research Laboratories (CORELAB), University of California, Los Angeles, California, USA
| | - Joanna Curry
- Cardiovascular Outcomes Research Laboratories (CORELAB), University of California, Los Angeles, California, USA
| | - Konmal Ali
- Cardiovascular Outcomes Research Laboratories (CORELAB), University of California, Los Angeles, California, USA
| | - Jeffrey Balian
- Cardiovascular Outcomes Research Laboratories (CORELAB), University of California, Los Angeles, California, USA
| | - Peyman Benharash
- Cardiovascular Outcomes Research Laboratories (CORELAB), University of California, Los Angeles, California, USA
- Department of Surgery, University of California, Los Angeles, California, USA
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Campos-Varela I, Castells L, Quiroga S, Vargas V, Simon-Talero M. Frailty and sarcopenia in patients with acute-on-chronic liver failure: Assessment and risk in the liver transplant setting. Ann Hepatol 2024; 29:101515. [PMID: 38851394 DOI: 10.1016/j.aohep.2024.101515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 12/17/2023] [Accepted: 05/31/2024] [Indexed: 06/10/2024]
Abstract
Frailty and sarcopenia are well-recognized factors related to worse outcomes in patients with cirrhosis, including liver transplant (LT) candidates. Implications of pre-LT functional and muscle deterioration also affect post-LT outcomes. Patients with cirrhosis and acute-on-chronic liver failure (ACLF) have a lower survival rate, both before and after LT. There is a need to better identify those patients with ACLF who would benefit from LT. This review aims to present the available data about frailty and sarcopenia in patients with ACLF in the LT setting. An exhaustive review of the published literature was conducted. Data regarding frailty and sarcopenia in LT candidates with ACLF are scarce and heterogeneous. Studies evaluating frailty and sarcopenia in critically ill patients outside the liver literature are also presented in this review to enrich the knowledge of this field in expansion. Frailty and sarcopenia seem to contribute to worse outcomes in LT candidates with ACLF, both before and after LT. Sarcopenia evaluation may be the most prudent approach for those very sick patients. Skeletal muscle index assessed by computed tomography is recommended to evaluate sarcopenia. The role of muscle ultrasound and bioelectrical impedance analysis is to be determined. Frailty and sarcopenia are crucial factors to consider on a case-by-case basis in LT candidates with ACLF to improve patient outcomes.
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Affiliation(s)
- Isabel Campos-Varela
- Liver Unit, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut of Research (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
| | - Lluis Castells
- Liver Unit, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut of Research (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Sergi Quiroga
- Radiology Department, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut of Research (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Victor Vargas
- Liver Unit, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut of Research (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Macarena Simon-Talero
- Liver Unit, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut of Research (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
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24
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Ahmed H, Atiq M, Salih M, Bhatti AB, Ullah F, Khan N, Zia H, Khan US, Bangash A, Ahmerin A, Aamir A. Impact of Sarcopenia on Post-Liver Transplant Hospitalization: Insights From a South Asian Cohort. Transplant Proc 2024; 56:1624-1632. [PMID: 39183081 DOI: 10.1016/j.transproceed.2024.08.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 08/05/2024] [Indexed: 08/27/2024]
Abstract
BACKGROUND Sarcopenia's impact on post-liver transplant outcomes remains a subject of debate, with limited data from South Asia on its association with post-liver transplant hospital stays. This study aims to investigate sarcopenia's influence on post-transplant hospitalization duration in South Asians. METHODS In this retrospective study, patients with liver cirrhosis who underwent living-donor liver transplantation (LDLT) at Shifa International Hospital in Islamabad, Pakistan, between January 2022 and January 2023 were included. Computed tomography (CT) images were used to assess the skeletal muscle index (SMI). The areas of the psoas, erector spinae, multifidus, quadratus lumborum, rectus abdominis, transverse abdominis, and internal/external oblique muscles were quantified at the level of L3. The data were analyzed using SPSS version 29.0 (IBM). RESULTS There was a total of 84 patients. Mean age was 47.4 ± 12.0 years. There were 62 (73.8%) male patients and 22 (26.2%) female patients. Hepatitis C was noted in 36 (42.9%) patients. Twenty-two (26.2%) patients had hepatocellular carcinoma. Sarcopenia was identified in 58 (69.0%) patients. No significant association was observed between sarcopenia and intensive care unit (ICU) or general floor stays. Regression analysis identified pre-transplant model for end-stage liver disease-sodium (MELD-Na) score as the sole significant factor associated with both ICU and total length of stay (P value .002; P value .009). CONCLUSION In our population, sarcopenia did not correlate with post-transplant ICU or overall hospital stay. The pre-transplant MELD-Na score emerged as the most influential predictor of length of stay. Therefore, delaying liver transplant procedures based on muscle mass estimations may not be a practical clinical approach for South Asian patients.
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Affiliation(s)
- Hamna Ahmed
- Department of Gastroenterology and Hepatology, Shifa International Hospital, Islamabad, Pakistan
| | - Muslim Atiq
- Department of Gastroenterology and Hepatology, Shifa International Hospital, Islamabad, Pakistan.
| | - Mohammad Salih
- Department of Gastroenterology and Hepatology, Shifa International Hospital, Islamabad, Pakistan
| | - Abu Bakar Bhatti
- Department of Hepatobiliary Surgery and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan
| | - Fazal Ullah
- Department of Radiology, Shifa International Hospital, Islamabad, Pakistan
| | - Nusrat Khan
- Department of Hepatobiliary Surgery and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan
| | - Haseeb Zia
- Department of Hepatobiliary Surgery and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan
| | - Usama Shujaatullah Khan
- Department of Gastroenterology and Hepatology, Shifa International Hospital, Islamabad, Pakistan
| | - Asfand Bangash
- Department of Gastroenterology and Hepatology, Shifa International Hospital, Islamabad, Pakistan
| | - Afaaf Ahmerin
- Department of Gastroenterology and Hepatology, Shifa International Hospital, Islamabad, Pakistan
| | - Amna Aamir
- Department of Gastroenterology and Hepatology, Shifa International Hospital, Islamabad, Pakistan
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25
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Harris SJ, Stine JG. Frailty in liver transplantation: Exploring prescribing exercise as medicine to improve patient outcomes. Liver Int 2024; 44:2251-2262. [PMID: 38899635 DOI: 10.1111/liv.15986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 05/08/2024] [Accepted: 05/14/2024] [Indexed: 06/21/2024]
Abstract
Liver transplantation (LT) represents a curative avenue for individuals with advanced chronic liver disease. Given the inherent illness severity of LT candidates, identifying patients at greater risk for adverse outcomes before and after transplantation is paramount. Approximately 50% of cirrhotic patients are frail and have considerable functional impairment. Various measures have been used to assess frailty, including performance-based tests and functional status evaluations. Frailty carries significant prognostic implications and predicts both mortality and pre- and post-LT complications. Contributing factors to frailty in this population include sarcopenia, malnutrition, inflammation, and psychosocial factors. Recognizing the prevalence of frailty among LT candidates, exercise interventions have been developed to improve physical frailty and offer potential to improve patient outcomes. While many interventions have demonstrated efficacy without notable adverse events, the absence of a universally accepted standard for exercise prescription underscores the variability in intervention elements and patient adherence. Given the safety profile of exercise interventions, there remains a critical need for standardized protocols and guidelines to optimize exercise regimens for LT candidates. This review delves into the landscape of frailty among LT candidates, elucidating its etiological underpinnings, impact on outcomes, utilization of exercise interventions, and the efficacy of exercise programs in reducing the burden frailty in those awaiting LT.
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Affiliation(s)
- Sara J Harris
- College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania, USA
| | - Jonathan G Stine
- Division of Gastroenterology and Hepatology, Department of Medicine, Penn State Health - Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA
- Fatty Liver Program, Penn State Health - Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA
- Liver Center, Penn State Health - Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA
- Department of Public Health Sciences, The Pennsylvania State University - College of Medicine, Hershey, Pennsylvania, USA
- Cancer Institute, Penn State Health - Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA
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26
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D'Arcangelo F, Zanetto A, Ferrarese A, Gambato M, Lanari J, Piano S, Germani G, Senzolo M, Russo FP, Angeli P, Cillo U, Burra P. Frailty and sarcopenia in patients with cirrhosis awaiting liver transplantation: evidence from a single-centre, prospective cohort study. Updates Surg 2024; 76:1807-1818. [PMID: 39102178 DOI: 10.1007/s13304-024-01962-9] [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: 02/23/2024] [Accepted: 07/30/2024] [Indexed: 08/06/2024]
Abstract
Sarcopenia and frailty are common complications in patients with cirrhosis evaluated for liver transplantation (LT). Although the negative impact of sarcopenia on patient's outcome has been well studied, the prognostic role of frailty is not as clear. We assessed the prevalence of sarcopenia and frailty and the clinical impact of frailty in a prospective cohort of cirrhosis patients with and without hepatocellular carcinoma (HCC) listed for LT. Patients with cirrhosis were prospectively recruited at the time of admission into the waiting list. Clinical and lab values were collected. Physical frailty was assessed by liver frailty index (LFI) and patients were categorized into robust (< 3.2); pre-frail (between 3.2 and 4.5), and frail (> 4.5). Skeletal muscle mass was evaluated via skeletal muscle index (SMI) obtained from last CT scan before LT; sarcopenia was defined by SMI < 50 cm2/m2 in males and < 39 cm2/m2 in females. 105 patients were included, of which 42 (40%) had hepatocellular carcinoma (HCC). In patients without HCC (63.5% males, median age 61 years), 36.5% were frail, 50.8% were pre-frail and 12.7% were robust. Frail patients were older than non-frail patients (63 vs. 56; p = 0.008) and had more severe liver disease (Child C: 65% vs. 37.5%; p = 0.02). Prevalence of sarcopenia in patients without HCC was 63%, with similar value of median SMI between frail and not frail patients (p = 0.454). Patients with HCC (78.6% males, 65 years old) were 21.4% frail, 61.9% pre-frail, and 16.7% robust. Frail patients had more severe liver disease (Child C: 77% vs. 18.2%; p = 0.004), whereas age was comparable to non-frail patients; among patients without HCC, during a median follow-up of 263 days, 17% died (of which 72% were frail) and 10 patients were delisted due to clinical improvement (none of whom were frail). Among those with HCC, during a median follow-up of 289 days, 4 (9%) patients died of which 50% were frail. Frailty and sarcopenia are common complications in patients with cirrhosis awaiting LT. Frailty appears to be associated with an increased risk of mortality during wait-list time especially in those with decompensated cirrhosis. At univariate analysis Meld score, Child score and presence of frailty were found to be associated with shorter survival, however, at multivariate analysis presence of frailty and Child C vs. A/B were the only independent predictor of death. Larger cohorts are required to confirm these results.
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Affiliation(s)
- Francesca D'Arcangelo
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, 35128, Padua, PD, Italy
| | - Alberto Zanetto
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, 35128, Padua, PD, Italy.
| | - Alberto Ferrarese
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, 35128, Padua, PD, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, 35128, Padua, PD, Italy
| | - Jacopo Lanari
- Hepato-Biliary-Pancreatic and Liver Transplant Unit, Padua University Hospital, Padua, Italy
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine - DIMED, University and Hospital of Padova, Padua, Italy
| | - Giacomo Germani
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, 35128, Padua, PD, Italy
| | - Marco Senzolo
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, 35128, Padua, PD, Italy
| | - Francesco Paolo Russo
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, 35128, Padua, PD, Italy
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology, Department of Medicine - DIMED, University and Hospital of Padova, Padua, Italy
| | - Umberto Cillo
- Hepato-Biliary-Pancreatic and Liver Transplant Unit, Padua University Hospital, Padua, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, 35128, Padua, PD, Italy
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Geladari E, Alexopoulos T, Vasilieva L, Tenta R, Mani I, Sevastianos V, Alexopoulou A. Evaluation of Five Screening Tools in Detecting Physical Frailty in Cirrhosis and Their Prognostic Role. J Clin Med 2024; 13:5169. [PMID: 39274382 PMCID: PMC11396431 DOI: 10.3390/jcm13175169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 08/12/2024] [Accepted: 08/27/2024] [Indexed: 09/16/2024] Open
Abstract
Background: Physical frailty (PF) is a syndrome of decreased physical function and reserves, preventing patients from coping with stressful events. PF screening tools in patients with liver cirrhosis (LC) can help evaluate the risk of complications and death. The aim of this study was to assess the performance of five screening tools in detecting PF and their ability to predict 18-month mortality in LC. Methods: The Short Physical Performance Battery (SPPB), Fried frailty phenotype (FFP), Clinical Frailty Scale (CFS) and 6-Minute Walk Test (6MWT) were compared with the Liver Frailty Index (LFI) as the method of reference. Patients with an LFI ≥ 4.5, SPPB ≤ 8, FFP ≥ 3, CFS ≥ 6 points, and those walking <250 m, were considered frail. Results: A total of 109 consecutive patients with stable LC were included [63.3% male, median age 62 years, (IQR 52-70), MELD 9 (7-14.5), 46.8% with decompensated LC (DC)]. PF was present in 23.9%, 27.5%, 41.3%, 13.8%, and 28.4% as assessed by the LFI, SPPB, FFP, CFS, and 6MWT, respectively. Cohen's kappa measurement of agreement of four of the tools with LFI was 0.568, 0.334, 0.439, and 0.502, respectively (p < 0.001 for each). Kaplan-Meier survival curves at 18 months showed higher mortality in frail patients compared to non-frail patients by any method (log rank p < 0.05). In the multivariate models, PF defined by any method emerged as an independent prognostic factor of 18-month mortality after adjustment for age, gender, and MELD-score. Conclusions: Patients characterized as frail by five screening tools were not identical. However, PF defined by either method was proven to be an independent poor prognostic factor for long-term mortality after adjustment for covariates.
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Affiliation(s)
- Eleni Geladari
- 3rd Department of Internal Medicine and Liver Outpatient Clinic, Evangelismos General Hospital, 10676 Athens, Greece
| | - Theodoros Alexopoulos
- Gastroenterology Department, Medical School, Laiko General Hospital, National & Kapodistrian University of Athens, 11527 Athens, Greece
| | - Larisa Vasilieva
- Department of Gastroenterology, Alexandra General Hospital, 11528 Athens, Greece
| | - Roxane Tenta
- Department of Nutrition & Dietetics, School of Health Sciences and Education, Harokopio University of Athens, 17676 Athens, Greece
| | - Iliana Mani
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Vassilios Sevastianos
- 3rd Department of Internal Medicine and Liver Outpatient Clinic, Evangelismos General Hospital, 10676 Athens, Greece
| | - Alexandra Alexopoulou
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
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Vincelette C, Mulongo P, Giard JM, Amzallag É, Carr A, Chaudhury P, Dajani K, Fugère R, Gonzalez-Valencia N, Joosten A, Kandelman S, Karvellas C, McCluskey SA, Özelsel T, Park J, Simoneau È, Trottier H, Chassé M, Carrier FM. Risk evaluation and recipient selection in adult liver transplantation: A mixed-methods survey. CANADIAN LIVER JOURNAL 2024; 7:352-367. [DOI: 10.3138/canlivj-2023-0037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Background: Liver transplant (LT) is the definitive treatment for end-stage liver disease. Limited resources and important post-operative implications for recipients compel judicious risk stratification and patient selection. However, little is known about the factors influencing physicians’ assessment regarding patient selection for LT and risk evaluation. Methods: We conducted a mixed-methods, cross-sectional survey involving Canadian hepatologists, anesthesiologists, LT surgeons, and French anesthesiologists. The survey contained quantitative questions and a vignette-based qualitative substudy about risk assessment and patient selection for LT. Descriptive statistics and qualitative content analyses were used. Results: We obtained answers from 129 physicians, and 63 participated in the qualitative substudy. We observed considerable variability in risk assessment prior to LT and identified many factors perceived to increase the risk of complications. Clinicians reported that the acceptable incidence of at least 1 severe post-operative complication for a LT program was 20% (95% CI: 20-30%). They identified the presence of any comorbidity as increasing the risk of different post-operative complications, especially acute kidney injury and cardiovascular complications. Frailty and functional disorders, severity of the liver disease, renal failure and cardiovascular comorbidities prior to LT emerged as important risk factors for post-operative morbidity. Most respondents were willing to pursue LT in patients with grade III acute-on-chronic liver failure but were less often willing to do so when faced with the uncertainty of a clinical example. Conclusions: Clinicians had a heterogeneous appraisal of the post-operative risk of complications following LT, as well as factors considered in risk assessment.
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Affiliation(s)
- Christian Vincelette
- Health Innovation and Evaluation Hub, Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Quebec, Canada
- Faculty of Medicine and Postdoctoral Studies, Université de Montréal, Montréal, Québec, Canada
| | - Philémon Mulongo
- School of Public Health, Université de Montréal, Montréal, Quebec, Canada
| | - Jeanne-Marie Giard
- Department of Medicine, Liver Disease Division, Centre hospitalier de l'Université de Montréal, Montréal, Quebec, Canada
| | - Éva Amzallag
- Health Innovation and Evaluation Hub, Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Quebec, Canada
| | - Adrienne Carr
- Department of Anesthesiology, Pain Management & Perioperative Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Prosanto Chaudhury
- Department of Surgery, McGill University Health Centre, Montréal, Quebec, Canada
| | - Khaled Dajani
- Department of Surgery, University Health Centre, University of Alberta, Edmonton, Alberta, Canada
| | - Réné Fugère
- Canadian Donation and Transplantation Research Program, Edmonton, Alberta, Canada
| | - Nelson Gonzalez-Valencia
- Department of Anesthesiology and Perioperative Medicine, Western University and London Health Sciences Centre, London, Ontario, Canada
| | - Alexandre Joosten
- Department of Anesthesiology & Perioperative Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, United States
| | - Stanislas Kandelman
- Department of Anesthesiology, McGill University Health Centre, Montréal, Quebec, Canada
| | - Constantine Karvellas
- Division of Gastroenterology (Liver Unit), Department of Critical Care Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Stuart A. McCluskey
- Department of Anesthesia and Pain Management, Toronto General Hospital, Toronto, Ontario, Canada
- Department of Anesthesiology & Pain Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Timur Özelsel
- Department of Anesthesiology & Pain Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Jeieung Park
- Department of Anesthesiology and Perioperative Care, Vancouver General Hospital, Vancouver, British Columbia, Canada
- Department of Anesthesiology, Pharmacology & Therapeutics, The University of British Colombia, Vancouver, British Columbia, Canada
| | - Ève Simoneau
- Hepatobiliary Division, Department of Surgery, Centre hospitalier de l'Université de Montréal, Montréal, Quebec, Canada
| | - Helen Trottier
- Department of Social and Preventive Medicine, École de santé publique de l'Université de Montréal, Montréal, Quebec, Canada
| | - Michaël Chassé
- Department of Anesthesiology, Pain Management & Perioperative Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
- Critical Care Division, Department of Medicine, Centre hospitalier de l'Université de Montréal, Montréal, Canada
- Department of Medicine, Université de Montréal, Montréal, Quebec, Canada
| | - François Martin Carrier
- Department of Anesthesiology, Pain Management & Perioperative Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
- Critical Care Division, Department of Medicine, Centre hospitalier de l'Université de Montréal, Montréal, Canada
- Department of Anesthesiology and Pain Medicine, Université de Montréal, Montréal, Quebec, Canada
- Correspondence: François Martin Carrier, MD, MSc, PhD(c) Département d'anesthésiologie, Centre hospitalier de l'Université de Montréal (CHUM), 4e étage, Pavillon D, porte D04-5031, 1000, rue St-Denis, Montréal, Québec H2 × 0C1, Canada. Tel: 514-890-8000, #12132
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Gabrielli F, Biagi F, Avossa A, Falcini M, Nascimbeni F, Andreone P, Gitto S. Frailty after Liver Transplantation: A Complex Unexplored Issue. J Clin Med 2024; 13:4537. [PMID: 39124803 PMCID: PMC11313396 DOI: 10.3390/jcm13154537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 07/30/2024] [Accepted: 07/31/2024] [Indexed: 08/12/2024] Open
Abstract
Frailty is a multidimensional syndrome predominantly studied in the elderly, characterized by reduced resistance to stressors due to diminished physiological reserve and resilience. Advances in surgical techniques and immunosuppressive drugs have improved long-term survival rates in solid organ transplant recipients, yet the 10-year survival is satisfying. However, liver transplant recipients have a noteworthy risk of developing frailty status. After liver transplant, frailty can be favored by socioeconomic, cultural, and health-related factors, leading to increased risks of hospitalization, morbidity, and mortality. Various tools for frailty assessment exist, but none are universally validated for post-transplant patients. The integration of socioeconomic and psychological factors into frailty evaluation could improve quality of life and long-term outcomes for transplant recipients. Multidisciplinary approaches, including psychosocial support, are essential for managing frailty and enhancing the overall care of transplanted patients. This narrative review aims to comprehensively address the principal frailty risk factors associated with liver transplantation.
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Affiliation(s)
- Filippo Gabrielli
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU of Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy; (F.G.)
- Department of Surgical Sciences, University of Bologna, 40126 Bologna, Italy
| | - Filippo Biagi
- Internal Medicine, University Hospital Careggi and Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
| | - Alessandra Avossa
- Internal Medicine, University Hospital Careggi and Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
| | - Margherita Falcini
- Internal Medicine, University Hospital Careggi and Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
| | - Fabio Nascimbeni
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU of Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy; (F.G.)
| | - Pietro Andreone
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU of Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy; (F.G.)
- Postgraduate School of Allergology and Clinical Immunology, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Stefano Gitto
- Internal Medicine, University Hospital Careggi and Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
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Jutras G, Lai JC. The Liver Frailty Index: a model for establishing organ-specific frailty metrics across all solid organ transplantation. Curr Opin Organ Transplant 2024; 29:266-270. [PMID: 38836426 DOI: 10.1097/mot.0000000000001157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2024]
Abstract
PURPOSE OF REVIEW In this review, we discuss the development of the Liver Frailty Index (LFI) and how it may serve as a model for developing other organ-specific frailty indices. RECENT FINDINGS As the demand for solid organ transplants continues to increase, the transplantation community is enhancing its strategies for organ allocation to gain deeper insights into patient risk profiles and anticipated outcomes. Frailty has emerged as a critical concept in transplant care, offering valuable insights into adverse health outcomes. Standardizing frailty assessment across transplant programs could enhance prognostic accuracy and inform pretransplant interventions.The LFI comprises of three performance-based tests that each represents essential components of the multidimensional frailty construct. This composite metric provides insights beyond liver function and considers nonhepatic comorbid factors. Identifying common frailty principles among all transplant candidates and adopting the LFI methodology, which assesses fundamental frailty principles using liver-specific tools, could establish a foundational pool of shared core frailty principles. From this pool, organ-specific frailty indices could be derived, each equipped with the clinically relevant organ-specific tools to evaluate common core principles. SUMMARY Creating a standardized framework across all solid-organ transplants, with common principles and organ-specific measurements, would facilitate consistent frailty assessment, standardize the integration of the frailty construct into transplant decision-making, and enable center-level interventions to improve outcomes for patients with end-stage organ disease.
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Affiliation(s)
- Gabrielle Jutras
- Department of Medicine, Division of Hepatology, Centre Hospitalier de l'Université de Montréal (CHUM), University of Montreal, Montreal, Quebec, Canada
| | - Jennifer C Lai
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California - San Francisco, California, USA
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Sepulveda A, Pravisani R. Artificial intelligence and liver transplantation: looking inside the Pandora’s box. ARTIFICIAL INTELLIGENCE SURGERY 2024; 4:170-9. [DOI: 10.20517/ais.2024.11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Artificial intelligence (AI) is the discipline of computer science dedicated to processing a large amount of throughput data and is based on algorithms that can rationalize increasingly complex tasks and ultimately reproduce human intelligence. It has been speculated for clinical uses in liver transplantation (LT) for several years, but its application remains incipient worldwide. Therefore, the recent advancements of digital and robotic tools in daily medical practice make the modern environment propitious to its proper implementation. Nevertheless, it is noteworthy that this technology has significant limitations: (i) its unconditional dependence on a pre-established reliable and extensive database; (ii) the potential impact on independent medical decision-making; and (iii) a major economic and environmental burden. So, despite its seducing and flawless simplicity features, AI emerges as a new “Pandora’s box” that should be carefully understood and used under the light of ethical principles to improve clinical outcomes, promote medical and para-medical working conditions, and increase patient safety and access to medical care. The present work aims to review literature data supporting AI implementation on this basis.
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He Y, Wang Z, Wu S, Li L, Li J, Zhang Y, Chen B, Sun X, Sun C, Wu L. Screening and assessment of malnutrition in patients with liver cirrhosis. Front Nutr 2024; 11:1398690. [PMID: 39091687 PMCID: PMC11292113 DOI: 10.3389/fnut.2024.1398690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Accepted: 07/09/2024] [Indexed: 08/04/2024] Open
Abstract
The development and advancement of malnutrition is associated not only with the progression of hepatic dysfunction, but also with cirrhosis-related complications. However, the prevalence of malnutrition reported in different studies varies widely due to differences in diagnostic methods and patient investigation settings. Therefore, we need to identify malnourished patients promptly and accurately. The purpose of this review was to compare the validity and reliability of nutritional screening tools and to select the most appropriate nutritional risk screening for patients with cirrhosis. We compared nutritional risk screening tools such as the Nutritional Risk Screening 2002 (NRS-2002), Malnutrition Universal Screening Tool (MUST), Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) and Liver Disease Undernutrition Screening Tool (LDUST). Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) is more feasible to screen cirrhotic patients for nutritional risk, and is highly reproducible, considering the impact of sodium and water retention; so it is practical to screen cirrhotic patients via RFH-NPT for nutritional risk, subsequently, to evaluate the nutritional status of patients with nutritional risk via the Global Leadership Initiative on Malnutrition (GLIM) diagnostic criteria. L3-SMI (third lumbar-skeletal muscle index) can accurately define sarcopenia in cirrhotic patients and also be used for clinical nutritional status assessment.
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Affiliation(s)
- Yumei He
- North Sichuan Medical College, Nanchong, China
- Department of Gastroenterology, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, China
| | - Zhiming Wang
- Department of Gastroenterology, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, China
| | - Shiyan Wu
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Lu Li
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Jiazhen Li
- Department of Clinical Nutrition, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, China
| | - Yexing Zhang
- Department of Gastroenterology, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, China
| | - Boshi Chen
- Department of Gastroenterology, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, China
| | - Xiaobin Sun
- Department of Gastroenterology, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, China
| | - Chao Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Liping Wu
- Department of Gastroenterology, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, China
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Nazir S, Abbas Z, Amjad S, Altaf A, Qadeer MA, Maqbool S, Siyal M, Kumar M. Prevalence of Osteosarcopenia and Frailty in Patients with Chronic Liver Disease. Euroasian J Hepatogastroenterol 2024; 14:156-159. [PMID: 39802856 PMCID: PMC11714115 DOI: 10.5005/jp-journals-10018-1442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Accepted: 08/02/2024] [Indexed: 01/16/2025] Open
Abstract
Introduction Chronic liver disease (CLD) can have a significant impact on the nutritional status of patients. Malnutrition is an under-recognized condition in patients with cirrhosis. Malnutrition increases the incidence and severity of decompensation, increases the risk of infections, and increases mortality. The present study aimed to assess osteosarcopenia and frailty in patients with CLD. Materials and methods This prospective cross-sectional study included 151 cases of CLD, aged between 18 and 85 years. Anthropometric measurements were performed. Sarcopenia was assessed by handgrip strength using a hand-held dynamometer. Bone mineral density was measured with the help of an office-based DEXA scan (Osteosys). Liver frailty was assessed through performance-based tests. Results Out of 151 patients, 98 were male (69.5%); mean age was 51.8 ± 13.2. The presarcopenia was seen in 91 (60%) patients, and sarcopenia in 45(30%). Osteopenia was present in 75 (50%) and osteoporosis in 24 (16%). The patients with osteopenia and osteoporosis had a high liver frailty index (LFI) (p-value < 0.001). A significant correlation between body mass index, waist circumference, LFI, calcium level, bilirubin and Child Pugh scores was seen with T and Z scores. Factors associated with low bone mineral density included increasing age and LFI, low calcium and higher PTH. Conclusion There is a high prevalence of pre-sarcopenia, sarcopenia, osteopenia, osteoporosis and high frailty in our patients with CLD. Early detection and timely intervention in these conditions are important to reduce the associated consequences. All patients with CLD should be assessed for osteosarcopenia and frailty, both at baseline and longitudinally. How to cite this article Nazir S, Abbas Z, Amjad S, et al. Prevalence of Osteosarcopenia and Frailty in Patients with Chronic Liver Disease. Euroasian J Hepato-Gastroenterol 2024;14(2):156-159.
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Affiliation(s)
- Shamim Nazir
- Department of Gastroenterology and Hepatology, Dr. Ziauddin Hospital Clifton Campus, Karachi, Pakistan
| | - Zaigham Abbas
- Department of Gastroenterology and Hepatology, Dr. Ziauddin Hospital Clifton Campus, Karachi, Pakistan
| | - Shaima Amjad
- Department of Gastroenterology and Hepatology, Dr. Ziauddin Hospital Clifton Campus, Karachi, Pakistan
| | - Abeer Altaf
- Department of Gastroenterology and Hepatology, Dr. Ziauddin Hospital Clifton Campus, Karachi, Pakistan
| | - Muhammad Ali Qadeer
- Department of Gastroenterology and Hepatology, Dr. Ziauddin Hospital Clifton Campus, Karachi, Pakistan
| | - Sania Maqbool
- Department of Gastroenterology and Hepatology, Dr. Ziauddin Hospital Clifton Campus, Karachi, Pakistan
| | - Mehreen Siyal
- Department of Gastroenterology and Hepatology, Dr. Ziauddin Hospital Clifton Campus, Karachi, Pakistan
| | - Manesh Kumar
- Department of Gastroenterology and Hepatology, Dr. Ziauddin Hospital Clifton Campus, Karachi, Pakistan
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Kirchner VA, Badshah JS, Kyun Hong S, Martinez O, Pruett TL, Niedernhofer LJ. Effect of Cellular Senescence in Disease Progression and Transplantation: Immune Cells and Solid Organs. Transplantation 2024; 108:1509-1523. [PMID: 37953486 PMCID: PMC11089077 DOI: 10.1097/tp.0000000000004838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2023]
Abstract
Aging of the world population significantly impacts healthcare globally and specifically, the field of transplantation. Together with end-organ dysfunction and prolonged immunosuppression, age increases the frequency of comorbid chronic diseases in transplant candidates and recipients, contributing to inferior outcomes. Although the frequency of death increases with age, limited use of organs from older deceased donors reflects the concerns about organ durability and inadequate function. Cellular senescence (CS) is a hallmark of aging, which occurs in response to a myriad of cellular stressors, leading to activation of signaling cascades that stably arrest cell cycle progression to prevent tumorigenesis. In aging and chronic conditions, senescent cells accumulate as the immune system's ability to clear them wanes, which is causally implicated in the progression of chronic diseases, immune dysfunction, organ damage, decreased regenerative capacity, and aging itself. The intimate interplay between senescent cells, their proinflammatory secretome, and immune cells results in a positive feedback loop, propagating chronic sterile inflammation and the spread of CS. Hence, senescent cells in organs from older donors trigger the recipient's alloimmune response, resulting in the increased risk of graft loss. Eliminating senescent cells or attenuating their inflammatory phenotype is a novel, potential therapeutic target to improve transplant outcomes and expand utilization of organs from older donors. This review focuses on the current knowledge about the impact of CS on circulating immune cells in the context of organ damage and disease progression, discusses the impact of CS on abdominal solid organs that are commonly transplanted, and reviews emerging therapies that target CS.
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Affiliation(s)
- Varvara A. Kirchner
- Division of Abdominal Transplantation, Department of Surgery, Stanford University, Stanford, CA
| | - Joshua S. Badshah
- Division of Abdominal Transplantation, Department of Surgery, Stanford University, Stanford, CA
| | - Suk Kyun Hong
- Division of Abdominal Transplantation, Department of Surgery, Stanford University, Stanford, CA
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Olivia Martinez
- Division of Abdominal Transplantation, Department of Surgery, Stanford University, Stanford, CA
| | - Timothy L. Pruett
- Division of Transplantation, Department of Surgery, University of Minnesota, Minneapolis, MN
| | - Laura J. Niedernhofer
- Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Medical School, Minneapolis, MN
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Olson SL, Polineni P, Schwartz WAH, Thuluvath AJ, Duarte-Rojo A, Ladner DP. Comparing Functional Frailty and Radiographic Sarcopenia as Predictors of Outcomes After Liver Transplant. Clin Transplant 2024; 38:e15412. [PMID: 39049617 PMCID: PMC12036958 DOI: 10.1111/ctr.15412] [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: 01/09/2024] [Revised: 06/12/2024] [Accepted: 07/04/2024] [Indexed: 07/27/2024]
Abstract
INTRODUCTION Frailty and sarcopenia are associated with an increased risk of hospitalization and mortality in patients with end-stage liver disease. The ability to identify frail patients at risk of adverse outcomes could help optimize liver transplant (LT) evaluations and pre-transplant care. This study compared sarcopenia, via L3-psoas muscle index (L3-PMI), to frailty, via liver frailty index (LFI) and analyzed associated outcomes after liver transplantation (LT). METHODS A retrospective review of consecutive LT-recipients with cross-sectional abdominal/pelvic imaging were reviewed over 5 years at a single transplant center. RESULTS Four hundred and twenty-six patients underwent transplant during this study interval; 31% of patients were sarcopenic. Two hundred eight patients underwent LFI evaluation: 25% were frail, 59% were prefrail, and 16% were robust. Sarcopenic patients had higher LFI scores indicating greater frailty (p = 0.02). Both sarcopenia and LFI-frailty were associated with significantly higher MELD-Na scores. Length of post-LT hospital stay was increased in sarcopenic (mean 14 vs. nonsarcopenic 11 days, p = 0.02) and LFI-frail patients (mean 13 vs. 10 prefrail, 8 robust, p = 0.04). As a categorical variable, neither LFI-frailty nor sarcopenia were significantly associated with reduced survival at 1-year (robust 100%, prefrail 93.5%, frail 91.1%, p = 0.31) (nonsarcopenic 94.4%, sarcopenic 91.4%, p = 0.30). However, LFI score was significantly associated with mortality at 1-year (OR 2.133, p = 0.047). CONCLUSIONS Radiographic sarcopenia is a suitable proxy for in-person frailty assessment as both L3-PMI and LFI capture frail patients' pre-LT. However, physical assessment with frailty better predicts 1-year mortality post-LT than the measurement of muscle mass.
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Affiliation(s)
- Sydney L. Olson
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Feinberg School of Medicine, Northwestern University, Chicago, Illinois
- Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, MD
| | - Praneet Polineni
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - William Alexander Henry Schwartz
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Avesh J. Thuluvath
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Andres Duarte-Rojo
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Feinberg School of Medicine, Northwestern University, Chicago, Illinois
- Division of Gastroenterology, Northwestern Medicine, Northwestern University, Chicago, IL
| | - Daniela P. Ladner
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center (CTC), Feinberg School of Medicine, Northwestern University, Chicago, Illinois
- Division of Transplant, Department of Surgery, Northwestern Medicine, Chicago, IL
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Liu G, Yi Y, Wang Y, Feng Y, Lin M, Yan X, Wang J, Ning X, Ma N. Assessment of the Risk of Malnutrition or Frailty Among Patients Undergoing Liver Transplantation: A Hospital-Based Prospective Study. Int J Gen Med 2024; 17:2347-2354. [PMID: 38799201 PMCID: PMC11128220 DOI: 10.2147/ijgm.s448154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Accepted: 05/08/2024] [Indexed: 05/29/2024] Open
Abstract
Objective We aimed to explore the status of nutritional and frailty in patients undergoing liver transplantation and the associated influencing factors. Methods We conducted a follow-up analysis of 44 patients who underwent liver transplantation between 2021 and 2022. We followed up and recorded the nutritional status and risk of weakness at different time-points (days 1, 2, 3, 6, 9, and 12) postoperatively. Patient information regarding demographics, physical examination, medical history, and perioperative blood tests were collected. Binary logistic regression was applied to identify risk factors for weakness after liver transplantation. Results The cohort comprised 44 liver transplant recipients, with a mean age of 47.66 years (standard deviation=9.49 years). Initial analysis revealed that, compared to the group without nutritional risks, the group with nutritional risks displayed elevated age and preoperative blood ammonia levels one week post-surgery. Moreover, this group had reduced levels of albumin and total bile acid preoperatively. Patients with preoperative nutritional risks were also prone to similar risks 2 weeks postoperatively. Further, a correlation was observed between preoperative pulmonary infections and increased frailty risk 6 days postoperatively. At both 9 and 12 days postoperatively, patients with frailty risk exhibited higher preoperative white blood cell counts and ammonia levels than those without. Multivariable analysis, controlling for confounding factors, indicated a significant association between preoperative nutritional status and nutritional risk 2 weeks postoperatively, as well as a link between preoperative white blood cell count and frailty risk at 12 days postoperatively. Conclusion There was a significant correlation between preoperative nutritional status and nutritional risk 2 weeks after liver transplantation, and preoperative white blood cell count was an independent risk factor for weakness 12 days postoperatively. Preoperative nutritional management for patients could potentially mitigate the likelihood of adverse clinical outcomes.
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Affiliation(s)
- Guiqing Liu
- Department of Liver Surgery (Liver Transplantation), Shenzhen Third People’s Hospital and the Second Hospital Affiliated with the Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China
| | - Yuanyuan Yi
- Department of Liver Surgery (Liver Transplantation), Shenzhen Third People’s Hospital and the Second Hospital Affiliated with the Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China
| | - Yanni Wang
- Department of Liver Surgery (Liver Transplantation), Shenzhen Third People’s Hospital and the Second Hospital Affiliated with the Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China
| | - Yuru Feng
- Department of Liver Surgery (Liver Transplantation), Shenzhen Third People’s Hospital and the Second Hospital Affiliated with the Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China
| | - Minyi Lin
- Department of Liver Surgery (Liver Transplantation), Shenzhen Third People’s Hospital and the Second Hospital Affiliated with the Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China
| | - Xu Yan
- Department of Liver Surgery (Liver Transplantation), Shenzhen Third People’s Hospital and the Second Hospital Affiliated with the Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China
| | - Jinghua Wang
- Center of Clinical Epidemiology, Shenzhen Third People’s Hospital and the Second Hospital Affiliated with the Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China
| | - Xianjia Ning
- Center of Clinical Epidemiology, Shenzhen Third People’s Hospital and the Second Hospital Affiliated with the Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China
| | - Nan Ma
- Department of Liver Surgery (Liver Transplantation), Shenzhen Third People’s Hospital and the Second Hospital Affiliated with the Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China
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Wang M, Ge J, Ha N, Shui AM, Huang CY, Cullaro G, Lai JC. Clinical Characteristics Associated With Posttransplant Survival Among Adults 70 Years Old or Older Undergoing Liver Transplantation. J Clin Gastroenterol 2024; 58:516-521. [PMID: 37279205 PMCID: PMC10700658 DOI: 10.1097/mcg.0000000000001870] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 04/24/2023] [Indexed: 06/08/2023]
Abstract
GOALS We sought to identify pre-liver transplantation (LT) characteristics among older adults associated with post-LT survival. BACKGROUND The proportion of older patients undergoing deceased-donor liver transplantation (DDLT) has increased over time. STUDY We analyzed adult DDLT recipients in the United Network for Organ Sharing registry from 2016 through 2020, excluding patients listed as status 1 or with a model of end-stage liver disease exceptions for hepatocellular carcinoma. Kaplan-Meier methods were used to estimate post-LT survival probabilities among older recipients (age ≥70 y). Associations between clinical covariates and post-LT mortality were assessed using Cox regressions. RESULTS Of 22,862 DDLT recipients, 897 (4%) were 70 years old or older. Compared with younger recipients, older recipients had worse overall survival ( P < 0.01) (1 y: 88% vs 92%, 3 y: 77% vs 86%, and 5 y: 67% vs 78%). Among older adults, in univariate Cox regressions, dialysis [hazards ratio (HR): 1.96, 95% CI: 1.38-2.77] and poor functional status [defined as Karnofsky Performance Score (KPS) <40] (HR: 1.82, 95% CI: 1.31-2.53) were each associated with mortality, remaining significant on multivariable Cox regressions. The effect of dialysis and KPS <40 at LT on post-LT survival (HR: 2.67, 95% CI: 1.77-4.01) was worse than the effects of either KPS <40 (HR: 1.52, 95% CI: 1.03-2.23) or dialysis alone (HR: 1.44, 95% CI: 0.62-3.36). Older recipients with KPS >40 without dialysis had comparable survival rates compared with younger recipients ( P = 0.30). CONCLUSIONS While older DDLT recipients had worse overall post-LT survival compared with younger recipients, favorable survival rates were observed among older adults who did not require dialysis and had poor functional status. Poor functional status and dialysis at LT may be useful to stratify older adults at higher risk for poor post-LT outcomes.
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Affiliation(s)
- Melinda Wang
- Department of Medicine, University of California- San Francisco, San Francisco, CA
| | - Jin Ge
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California-San Francisco, San Francisco, CA
| | - Nghiem Ha
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California-San Francisco, San Francisco, CA
| | - Amy M. Shui
- Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, CA
| | - Chiung-Yu Huang
- Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, CA
| | - Giuseppe Cullaro
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California-San Francisco, San Francisco, CA
| | - Jennifer C. Lai
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California-San Francisco, San Francisco, CA
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Choudhury A, Adali G, Kaewdech A, Giri S, Kumar R. Liver Transplantation in Chronic Liver Disease and Acute on Chronic Liver Failure- Indication, Timing and Practices. J Clin Exp Hepatol 2024; 14:101347. [PMID: 38371606 PMCID: PMC10869905 DOI: 10.1016/j.jceh.2024.101347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Accepted: 01/19/2024] [Indexed: 02/20/2024] Open
Abstract
Liver transplantation (LT) is the second most common solid organ transplantation worldwide. LT is considered the best and most definitive therapeutic option for patients with decompensated chronic liver disease (CLD), hepatocellular carcinoma (HCC), acute liver failure (ALF), and acute-on-chronic liver failure (ACLF). The etiology of CLD shows wide geographical variation, with viral hepatitis being the major etiology in the east and alcohol-related liver disease (ALD) in the west. Non-alcoholic fatty liver disease (NAFLD) is on an increasing trend and is expected to be the most common etiology on a global scale. Since the first successful LT, there have been radical changes in the indications for LT. In many circumstances, not just the liver disease itself but factors such as extra-hepatic organ dysfunction or failures necessitate LT. ACLF is a dynamic syndrome that has extremely high short-term mortality. Currently, there is no single approved therapy for ACLF, and LT seems to be the only feasible therapeutic option for selected patients at high risk of mortality. Early identification of ACLF, stratification of patients according to disease severity, aggressive organ support, and etiology-specific treatment approaches have a significant impact on post-transplant outcomes. This review briefly describes the indications, timing, and referral practices for LT in patients with CLD and ACLF.
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Affiliation(s)
- Ashok Choudhury
- Department of Hepatology and Liver Transplant, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Gupse Adali
- Department of Gastroenterology and Hepatology, University of Health Sciences, Ümraniye, İstanbul, Turkey
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
| | - Suprabhat Giri
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneshwar, India
| | - Rahul Kumar
- Duke-NUS Academic Medical Centre, Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
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Kim DS, Yoon YI, Kim BK, Choudhury A, Kulkarni A, Park JY, Kim J, Sinn DH, Joo DJ, Choi Y, Lee JH, Choi HJ, Yoon KT, Yim SY, Park CS, Kim DG, Lee HW, Choi WM, Chon YE, Kang WH, Rhu J, Lee JG, Cho Y, Sung PS, Lee HA, Kim JH, Bae SH, Yang JM, Suh KS, Al Mahtab M, Tan SS, Abbas Z, Shresta A, Alam S, Arora A, Kumar A, Rathi P, Bhavani R, Panackel C, Lee KC, Li J, Yu ML, George J, Tanwandee T, Hsieh SY, Yong CC, Rela M, Lin HC, Omata M, Sarin SK. Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation. Hepatol Int 2024; 18:299-383. [PMID: 38416312 DOI: 10.1007/s12072-023-10629-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 12/18/2023] [Indexed: 02/29/2024]
Abstract
Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
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Affiliation(s)
- Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | | | | | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ho Joong Choi
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University College of Medicine, Yangsan, Republic of Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Cheon-Soo Park
- Department of Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Deok-Gie Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young Eun Chon
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Ilsan, Republic of Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Soek Siam Tan
- Department of Medicine, Hospital Selayang, Batu Caves, Selangor, Malaysia
| | - Zaigham Abbas
- Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - Ananta Shresta
- Department of Hepatology, Alka Hospital, Lalitpur, Nepal
| | - Shahinul Alam
- Crescent Gastroliver and General Hospital, Dhaka, Bangladesh
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Pravin Rathi
- TN Medical College and BYL Nair Hospital, Mumbai, India
| | - Ruveena Bhavani
- University of Malaya Medical Centre, Petaling Jaya, Selangor, Malaysia
| | | | - Kuei Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jun Li
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Ming-Lung Yu
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | | | | | | | | | - H C Lin
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Bunkyo City, Japan
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Puchades L, Herreras J, Cebrià i Iranzo MÀ, Reyes É, Crespo G, Rodríguez-Perálvarez M, Cortés L, Serrano T, Fernández-Yunquera A, Montalvá E, Berenguer M. Frailty Changes After Liver Transplantation. Results From a Spanish Multicenter Prospective Cohort Study. Transplant Direct 2024; 10:e1599. [PMID: 38529356 PMCID: PMC10962876 DOI: 10.1097/txd.0000000000001599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 12/06/2023] [Indexed: 03/27/2024] Open
Abstract
INTRODUCTION Until now, there has been limited evidence, primarily from US cohorts, focusing on frailty as a patient-oriented outcome after liver transplantation (LT). Our study aimed to explore the relationship between pre- and post-LT frailty in a multicenter European cohort of outpatients with cirrhosis undergoing LT. METHODS We conducted a prospective analysis of data from 180 LT recipients recruited between 2018 and 2020 from 5 Spanish centers. Participants underwent objective and subjective frailty assessments using the Liver Frailty Index (LFI) and the Subjective Clinician Assessment (SCA) pretransplant and at 3- and/or 6-mo posttransplant. RESULTS The median pretransplant LFI was 3.9, showing minimal change at 3 mo (3.8; P = 0.331) and improvement at 6-mo post-LT (3.6; P = 0.001). Conversely, the SCA significantly improved early post-LT: at 3 mo, poor SCA decreased from 11% to 1%, and good SCA increased from 54% to 89% (P < 0.001), remaining stable between 3- and 6-mo post-LT. Multivariable analysis revealed that each 0.1 increase in pretransplant LFI correlated with a reduced probability of being robust at 3-mo (odds ratio [OR] = 0.75; P < 0.001) and 6-mo post-LT (OR = 0.74; P < 0.001). There was poor concordance between SCA and LFI, with SCA underestimating frailty both pre- and post-LT (Kappa < 0.20). CONCLUSION In our European cohort, incomplete improvement of physical frailty was observed, with <20% achieving robust physical condition within 6-mo post-LT. The pretransplant LFI strongly predicted posttransplant frailty. As the SCA tends to overestimate physical function, we recommend using both subjective and objective tools for frailty assessment in LT candidates and recipients.
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Affiliation(s)
- Lorena Puchades
- Hepatology and Liver Transplantation Group, Medical Research Institute Hospital La Fe, Valencia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Valencia, Spain
| | - Julia Herreras
- Hepatology and Liver Transplantation Group, Medical Research Institute Hospital La Fe, Valencia, Spain
| | - Maria Àngels Cebrià i Iranzo
- Medical Research Institute Hospital La Fe, Hepatology and Liver Transplantation Group, Valencia, Spain
- Department of Physical Medicine and Rehabilitation, La Fe University Hospital, University of Valencia, Valencia, Spain
- Physiotherapy Department, University of Valencia, Valencia, Spain
| | - Érick Reyes
- Liver Unit, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Gonzalo Crespo
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Valencia, Spain
- Liver Unit, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Manuel Rodríguez-Perálvarez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Valencia, Spain
- Department of Hepatology and Liver Transplantation, University Hospital Reina Sofía, Córdoba University, IMIBIC, Córdoba, Spain
| | - Luis Cortés
- Liver Transplantation Unit, Department of Gastroenterology, University Hospital Lozano Blesa, Zaragoza, Spain
| | - Trinidad Serrano
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Valencia, Spain
- Liver Transplantation Unit, Department of Gastroenterology, University Hospital Lozano Blesa, Zaragoza, Spain
| | - Ainhoa Fernández-Yunquera
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Valencia, Spain
- Department of Gastroenterology, Gregorio Marañón University General Hospital, Madrid, Spain
| | - Eva Montalvá
- Hepatology and Liver Transplantation Group, Medical Research Institute Hospital La Fe, Valencia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Valencia, Spain
- Liver Transplantation Unit, Department of General Surgery, La Fe University Hospital, Valencia, Spain
| | - Marina Berenguer
- Hepatology and Liver Transplantation Group, Medical Research Institute Hospital La Fe, Valencia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Valencia, Spain
- Hepatology Unit, Department of Gastroenterology, La Fe University Hospital, University of Valencia, Medicine Department, Valencia, Spain
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Cruz C, Prado CM, Gillis C, Martindale R, Bémeur C, Lai JC, Tandon P. Nutritional aspects of prehabilitation in adults with cirrhosis awaiting liver transplant. Hepatology 2024:01515467-990000000-00825. [PMID: 38546288 PMCID: PMC11828479 DOI: 10.1097/hep.0000000000000818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Accepted: 01/20/2024] [Indexed: 04/21/2024]
Abstract
Malnutrition, sarcopenia (low muscle mass), and physical frailty have gained increasing recognition in candidates for liver transplant (LT) as these conditions can impact postoperative functional capacity. Multidimensional prehabilitation programs have been proposed as a safe intervention in adults awaiting LT but the nutritional pillar of prehabilitation has been understudied. This review summarizes the nutritional recommendations for prehabilitation for individuals with cirrhosis awaiting LT. Three major aspects of nutritional prehabilitation are discussed: (1) Assess: Evaluate nutritional status and assess for malnutrition, sarcopenia, and frailty to guide the nutritional prehabilitation intervention intensity, increasing across universal, targeted, and specialist levels; (2) Intervene: Prescribe a nutritional prehabilitation intervention to meet established nutrition guidelines in cirrhosis with a targeted focus on improving nutritional status and muscle health; (3) Reassess: Follow-up based on the required intensity of nutritional care with as needed intervention adjustment. Topics covered in the review include nutritional care levels for prehabilitation, energy prescriptions across body mass index strata, detailed considerations around protein intake (amount, distribution, and quality), carbohydrate and fat intake, other nutritional considerations, and the potential role of dietary supplements and nutraceuticals. Future research is warranted to more accurately evaluate energy needs, evaluate emerging dietary supplementation strategies, and establish the role of nutraceuticals alongside food-based interventions. While the general principles of nutritional prehabilitation are ready for immediate application, future large-scale randomized controlled trials in this space will help to quantify the benefit that can be gained by transitioning the LT approach from passive "transplant waitlist time" to active "transplant preparation time."
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Affiliation(s)
- Christofer Cruz
- Department of Medicine, Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
| | - Carla M. Prado
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
| | - Chelsia Gillis
- School of Human Nutrition, McGill University, Montreal, Quebec, Canada
- Departments of Anesthesia & Surgery, McGill University, Montreal, Quebec, Canada
| | - Robert Martindale
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California-San Francisco, San Francisco, California, USA
| | - Chantal Bémeur
- Department of Nutrition, Université de Montréal, Montreal, Quebec, Canada
| | - Jennifer C. Lai
- Department of Surgery, Oregon Health and Science University, Portland, Oregon, USA
| | - Puneeta Tandon
- Department of Medicine, Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
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Perdiguero GG, Spina JC, Martínez J, Savluk L, Saidman J, Bonifacio M, Bakken S, Padilla M, Gallego-Clemente E, Moreno-González V, De Santibañes M, Marciano S, De Santibañes E, Gadano A, Pekolj J, Abraldes JG, Mauro E. Enhancing ACLF prediction by integrating sarcopenia assessment and frailty in liver transplant candidates on the waiting list. JHEP Rep 2024; 6:100985. [PMID: 38384670 PMCID: PMC10879792 DOI: 10.1016/j.jhepr.2023.100985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 12/04/2023] [Accepted: 12/12/2023] [Indexed: 02/23/2024] Open
Abstract
Background & Aims Malnutrition, sarcopenia, and frailty are prevalent in cirrhosis. We aimed to assess the correlation between assessment tools for malnutrition, sarcopenia, and frailty in patients on the liver transplant (LT) waiting list (WL), and to identify a predictive model for acute-on-chronic liver failure (ACLF) development. Methods This prospective single-center study enrolled consecutive patients with cirrhosis on the WL for LT (May 2019-November 2021). Assessments included subjective global assessment, CT body composition, skeletal muscle index (SMI), ultrasound thigh muscle thickness, sarcopenia HIBA score, liver frailty index (LFI), hand grip strength, and 6-minute walk test at enrollment. Correlations were analyzed using Pearson's correlation. Competing risk regression analysis was used to assess the predictive ability of the liver- and functional physiological reserve-related variables for ACLF. Results A total of 132 patients, predominantly with decompensated cirrhosis (87%), were included. Our study revealed a high prevalence of malnutrition (61%), sarcopenia (61%), visceral obesity (20%), sarcopenic visceral obesity (17%), and frailty (10%) among participants. Correlations between the assessment tools for sarcopenia and frailty were poor. Sarcopenia by SMI remained prevalent when frailty assessments were not usable. After a median follow-up of 10 months, 39% of the patients developed ACLF on WL, while 28% experienced dropouts without ACLF. Multivariate analysis identified MELD-Na, SMI, and LFI as independent predictors of ACLF on the WL. The predictive model MELD-Na-sarcopenia-LFI had a C-statistic of 0.85. Conclusions The poor correlation between sarcopenia assessment tools and frailty underscores the importance of a comprehensive evaluation. The SMI, LFI, and MELD-Na independently predicted ACLF development in WL. These findings enhance our understanding of the relationship between sarcopenia, frailty, and ACLF in patients awaiting LT, emphasizing the need for early detection and intervention to improve WL outcomes. Impact and implications The relationship between sarcopenia and frailty assessment tools, as well as their ability to predict acute-on-chronic liver failure (ACLF) in patients on the liver transplant (LT) waiting list (WL), remains poorly understood. Existing objective frailty screening tests have limitations when applied to critically ill patients. The correlation between sarcopenia and frailty assessment tools was weak, suggesting that they may capture different phenotypes. Sarcopenia assessed by skeletal muscle index, frailty evaluated using the liver frailty index, and the model for end-stage liver disease-Na score independently predicted the development of ACLF in patients on the WL. Our findings support the integration of liver frailty index and skeletal muscle index assessments at the time of inclusion on the WL for LT. This combined approach allows for the identification of a specific patient subgroup with an increased susceptibility to ACLF, underscoring the importance of early implementation of targeted treatment strategies to improve outcomes for patients awaiting LT.
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Affiliation(s)
| | - Juan Carlos Spina
- Liver Transplant Unit, Hospital Italiano de Bs. As., Buenos Aires, Argentina
- Radiology Department, Hospital Italiano de Bs As, Buenos Aires, Argentina
| | - Jorge Martínez
- Liver Unit, Hospital Italiano de Bs. As., Buenos Aires, Argentina
| | - Lorena Savluk
- Liver Transplant Unit, Hospital Italiano de Bs. As., Buenos Aires, Argentina
- Radiology Department, Hospital Italiano de Bs As, Buenos Aires, Argentina
| | - Julia Saidman
- Radiology Department, Hospital Italiano de Bs As, Buenos Aires, Argentina
| | | | - Sofia Bakken
- Liver Transplant Unit, Hospital Italiano de Bs. As., Buenos Aires, Argentina
- Radiology Department, Hospital Italiano de Bs As, Buenos Aires, Argentina
| | - Marlene Padilla
- Liver Unit, Hospital Italiano de Bs. As., Buenos Aires, Argentina
| | | | | | | | - Sebastián Marciano
- Liver Unit, Hospital Italiano de Bs. As., Buenos Aires, Argentina
- Liver Transplant Unit, Hospital Italiano de Bs. As., Buenos Aires, Argentina
| | | | - Adrían Gadano
- Liver Unit, Hospital Italiano de Bs. As., Buenos Aires, Argentina
- Liver Transplant Unit, Hospital Italiano de Bs. As., Buenos Aires, Argentina
| | - Juan Pekolj
- Liver Transplant Unit, Hospital Italiano de Bs. As., Buenos Aires, Argentina
| | - Juan G. Abraldes
- Division of Gastroenterology, University of Alberta, CEGIIR, Edmonton, Canada
| | - Ezequiel Mauro
- Liver Unit, Hospital Italiano de Bs. As., Buenos Aires, Argentina
- Liver Transplant Unit, Hospital Italiano de Bs. As., Buenos Aires, Argentina
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Zhou J, Ye D, Zhang S, Ding J, Zhang T, Chen Z, Xu F, Ren S, Hu Z. The impact of Karnofsky performance status on prognosis of patients with hepatocellular carcinoma in liver transplantation. BMC Gastroenterol 2024; 24:85. [PMID: 38408903 PMCID: PMC10895807 DOI: 10.1186/s12876-024-03161-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 02/06/2024] [Indexed: 02/28/2024] Open
Abstract
BACKGROUND Functional performance as measured by the Karnofsky Performance Status (KPS) scale has been linked to the outcomes of liver transplant patients; however, the effect of KPS on the outcomes of the hepatocellular carcinoma (HCC) liver transplant population has not been fully elucidated. We aimed to investigate the association between pre-transplant KPS score and long-term outcomes in HCC patients listed for liver transplantation. METHODS Adult HCC candidates listed on the Scientific Registry of Transplant Recipients (SRTR) database from January 1, 2011 to December 31, 2017 were grouped into group I (KPS 80-100%, n = 8,379), group II (KPS 50-70%, n = 8,091), and group III (KPS 10-40%, n = 1,256) based on percentage KPS score at listing. Survival was compared and multivariable analysis was performed to identify independent predictors. RESULTS Patients with low KPS score had a higher risk of removal from the waiting list. The 5-year intent-to-treat survival was 57.7% in group I, 53.2% in group II and 46.7% in group III (P < 0.001). The corresponding overall survival was 77.6%, 73.7% and 66.3% in three groups, respectively (P < 0.001). Multivariable analysis demonstrated that KPS was an independent predictor of intent-to-treat survival (P < 0.001, reference group I; HR 1.19 [95%CI 1.07-1.31] for group II, P = 0.001; HR 1.63 [95%CI 1.34-1.99] for group III, P < 0.001) and overall survival(P < 0.001, reference group I; HR 1.16 [95%CI 1.05-1.28] for group II, P = 0.004; HR 1.53 [95%CI 1.26-1.87] for group III, P < 0.001). The cumulative 5-year recurrence rates was higher in group III patients (7.4%), compared with 5.2% in group I and 5.5% in group II (P = 0.037). However, this was not significant in the competing regression analysis. CONCLUSIONS Low pre-transplant KPS score is associated with inferior long-term survival in liver transplant HCC patients, but is not significantly associated with post-transplant tumor recurrence.
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Affiliation(s)
- Jie Zhou
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Afliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Danni Ye
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Afliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Siyao Zhang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, China
| | - Jiawei Ding
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, China
| | - Tao Zhang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, China
| | - Zheng Chen
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, China
| | - Fangshen Xu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, China
| | - Shenli Ren
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, China
| | - Zhenhua Hu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Afliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, China.
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Deng Y, Sato N. Global frailty screening tools: Review and application of frailty screening tools from 2001 to 2023. Intractable Rare Dis Res 2024; 13:1-11. [PMID: 38404737 PMCID: PMC10883846 DOI: 10.5582/irdr.2023.01113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 01/09/2024] [Accepted: 01/11/2024] [Indexed: 02/27/2024] Open
Abstract
As the aging population increases globally, health-related issues caused by frailty are gradually coming to light and have become a global health priority. Frailty leads to a significantly increased risk of falls, incapacitation, and death. Early screening leads to better prevention and management of frailty, increasing the possibility of reversing it. Developing assessment tools by incorporating disease states of older adults using effective interventions has become the most effective approach for preventing and controlling frailty. The most direct and effective tool for evaluating debilitating conditions is a frailty screening tool, but because there is no globally recognized gold standard, every country has its own scale for national use. The diversity and usefulness of the frailty screening tool has become a hot topic worldwide. In this article, we reviewed the frailty screening tool published worldwide from January 2001 to June 2023. We focused on several commonly used frailty screening tools. A systematic search was conducted using PubMed database, and the commonly used frailty screening tools were found to be translated and validated in many countries. Disease-specific scales were also selected to fit the disease. Each of the current frailty screening tools are used in different clinical situations, and therefore, the clinical practice applications of these frailty screening tools are summarized graphically to provide the most intuitive screening and reference for clinical practitioners. The frailty screening tools were categorized as (ⅰ) Global Frailty Screening Tools in Common; (ⅱ) Frailty Screening Tools in various countries; (ⅲ) Frailty Screening Tools for various diseases. As science and technology continue to advance, electronic frailty assessment tools have been developed and utilized. In the context of Coronavirus disease 2019 (COVID-19), electronic frailty assessment tools played an important role. This review compares the currently used frailty screenings tools, with a view to enable quick selection of the appropriate scale. However, further improvement and justification of each tool is needed to guide clinical practitioners to make better decisions.
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Affiliation(s)
- Yi Deng
- Graduate School of Nursing, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Naomi Sato
- Department of Clinical Nursing, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
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Williams FR, Quinlan J, Freer A, Morrison B, Sitch A, Hockey F, Klas N, Towey J, Perera TPR, Rajoriya N, Lord JM, Armstrong MJ. Duke Activity Status Index and Liver Frailty Index predict mortality in ambulatory patients with advanced chronic liver disease: A prospective, observational study. Aliment Pharmacol Ther 2024; 59:547-557. [PMID: 38173029 DOI: 10.1111/apt.17834] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 07/08/2023] [Accepted: 12/02/2023] [Indexed: 01/05/2024]
Abstract
BACKGROUND There remains a lack of consensus on how to assess functional exercise capacity and physical frailty in patients with advanced chronic liver disease (CLD) being assessed for liver transplantation (LT). Aim To investigate prospectively the utility of the Duke Activity Status Index (DASI) and Liver Frailty Index (LFI) in ambulatory patients with CLD. AIM To investigate prospectively the utility of the Duke Activity Status Index (DASI) and Liver Frailty Index (LFI) in ambulatory patients with CLD. METHODS We recruited patients from outpatient clinics at University Hospitals Birmingham, UK (2018-2019). We prospectively collated the DASI and LFI to identify the prevalence of, respectively, functional capacity and physical frailty, and to evaluate their accuracy in predicting overall and pre-LT mortality. RESULTS We studied 307 patients (57% male; median age 54 years; UKELD 52). Median DASI score was 28.7 (IQR 16.2-50.2), mean LFI was 3.82 (SD = 0.72), and 81% were defined either 'pre-frail' or 'frail'. Female sex and hyponatraemia were significant independent predictors of both DASI and LFI. Age and encephalopathy were significant independent predictors of LFI, while BMI significantly predicted DASI. DASI and LFI were significantly related to overall (HR 0.97, p = 0.001 [DASI], HR 2.04, p = 0.001 [LFI]) and pre-LT mortality (HR 0.96, p = 0.02 [DASI], HR 1.94, p = 0.04 [LFI]). CONCLUSIONS Poor functional exercise capacity and physical frailty are highly prevalent among ambulatory patients with CLD who are being assessed for LT. The DASI and LFI are simple, low-cost tools that predict overall and pre-LT mortality. Implementation of both should be considered in all outpatients with CLD to highlight those who may benefit from targeted nutritional and exercise interventions.
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Affiliation(s)
- Felicity R Williams
- NIHR Birmingham Biomedical Research Centre, University Hospital Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK
- School of Sports, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK
- Liver Transplant Unit, Queen Elizabeth University Hospitals Birmingham, Birmingham, UK
| | - Jonathan Quinlan
- NIHR Birmingham Biomedical Research Centre, University Hospital Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK
- School of Sports, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK
| | - Alice Freer
- Therapies Department, Queen Elizabeth University Hospitals Birmingham, Birmingham, UK
| | - Breanna Morrison
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Alice Sitch
- NIHR Birmingham Biomedical Research Centre, University Hospital Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Florence Hockey
- Medical and Dental School, University of Birmingham, Birmingham, UK
| | - Natasza Klas
- Medical and Dental School, University of Birmingham, Birmingham, UK
| | - Jennifer Towey
- Therapies Department, Queen Elizabeth University Hospitals Birmingham, Birmingham, UK
| | - Thamara P R Perera
- Liver Transplant Unit, Queen Elizabeth University Hospitals Birmingham, Birmingham, UK
| | - Neil Rajoriya
- NIHR Birmingham Biomedical Research Centre, University Hospital Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK
- Liver Transplant Unit, Queen Elizabeth University Hospitals Birmingham, Birmingham, UK
| | - Janet M Lord
- NIHR Birmingham Biomedical Research Centre, University Hospital Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK
- Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
| | - Matthew J Armstrong
- NIHR Birmingham Biomedical Research Centre, University Hospital Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK
- Liver Transplant Unit, Queen Elizabeth University Hospitals Birmingham, Birmingham, UK
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Wijma AG, Bongers BC, Annema C, Dekker R, Blokzijl H, van der Palen JA, De Meijer VE, Cuperus FJ, Klaase JM. 'Effects of a home-based bimodal lifestyle intervention in frail patients with end-stage liver disease awaiting orthotopic liver transplantation': study protocol of a non-randomised clinical trial. BMJ Open 2024; 14:e080430. [PMID: 38286689 PMCID: PMC10826538 DOI: 10.1136/bmjopen-2023-080430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Accepted: 01/17/2024] [Indexed: 01/31/2024] Open
Abstract
INTRODUCTION Patients with end-stage liver disease awaiting orthotopic liver transplantation (OLT) are generally classified as frail due to disease-related malnutrition and a progressive decline in musculoskeletal and aerobic fitness, which is associated with poor pre-OLT, peri-OLT and post-OLT outcomes. However, frailty in these patients may be reversable with adequate exercise and nutritional interventions. METHODS AND ANALYSIS Non-randomised clinical trial evaluating the effect of a home-based bimodal lifestyle programme in unfit patients with a preoperative oxygen uptake (VO2) at the ventilatory anaerobic threshold ≤13 mL/kg/min and/or VO2 at peak exercise ≤18 mL/kg/min listed for OLT at the University Medical Center Groningen (UMCG). The programme is patient tailored and comprises high-intensity interval and endurance training, and functional exercises three times per week, combined with nutritional support. Patients will go through two training periods, each lasting 6 weeks.The primary outcome of this study is the impact of the programme on patients' aerobic fitness after the first study period. Secondary outcomes include aerobic capacity after the second study period, changes in sarcopenia, anthropometry, functional mobility, perceived quality of life and fatigue, incidence of hepatic encephalopathy and microbiome composition. Moreover, number and reasons of intercurrent hospitalisations during the study and postoperative outcomes up to 12 months post OLT will be recorded. Finally, feasibility of the programme will be assessed by monitoring the participation rate and reasons for non-participation, number and severity of adverse events, and dropout rate and reasons for dropout. ETHICS AND DISSEMINATION This study was approved by the Medical Research Ethics Committee of the UMCG (registration number NL83612.042.23, August 2023) and is registered in the Clinicaltrials.gov register (NCT05853484). Good Clinical Practice guidelines and the principles of the Declaration of Helsinki will be applied. Results of this study will be submitted for presentation at (inter)national congresses and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER NCT05853484.
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Affiliation(s)
- Allard G Wijma
- Department of Surgery, division of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
| | - Bart C Bongers
- Department of Nutrition and Movement Sciences, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands
- Department of Surgery, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands
| | - Coby Annema
- Section of Nursing Science, Department of Health Sciences, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
| | - Rienk Dekker
- Department for Rehabilitation Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Hans Blokzijl
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Job Am van der Palen
- Department of Epidemiology, Medisch spectrum Twente, Enschede, Netherlands
- Section Cognition, Data and Education, Faculty of Behavioural, Management and Social Sciences, University of Twente, Enschede, Netherlands
| | - Vincent E De Meijer
- Department of Surgery, division of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
| | - Frans Jc Cuperus
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Joost M Klaase
- Department of Surgery, division of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
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Ferretti S, Barreyro FJ. Worldwide Increasing Prevalence of Non-alcoholic Steatohepatitis as an Indication of Liver Transplantation: Epidemiological View and Implications. CURRENT HEPATOLOGY REPORTS 2024; 23:193-203. [DOI: 10.1007/s11901-023-00628-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 12/18/2023] [Indexed: 01/05/2025]
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Duarte-Rojo A, Bux R, Sliwa J. Untangling frailty, sarcopenia, and physical fitness in cirrhosis. Clin Liver Dis (Hoboken) 2024; 23:e0213. [PMID: 38841195 PMCID: PMC11152786 DOI: 10.1097/cld.0000000000000213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 04/01/2024] [Indexed: 06/07/2024] Open
Affiliation(s)
- Andres Duarte-Rojo
- Division of Gastroenterology and Hepatology, Northwestern Feinberg School of Medicine; Chicago, Illinois, USA
- Comprehensive Transplant Center, Northwestern Medicine, Chicago, Illinois, USA
| | - Rehaan Bux
- Comprehensive Transplant Center, Northwestern Medicine, Chicago, Illinois, USA
| | - James Sliwa
- Shirley Ryan Ability Lab, Department of Physical Medicine & Rehabilitation, Northwestern Feinberg School of Medicine, Chicago, Illinois, USA
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Li L, Fu X, He N, Gan W, Zhao Y, Xie R. Association of frailty with activity levels and sedentary behaviours in patients with hepatitis B cirrhosis: A cross-sectional study. Nurs Open 2024; 11:e2056. [PMID: 38268270 PMCID: PMC10714020 DOI: 10.1002/nop2.2056] [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: 05/08/2023] [Revised: 10/24/2023] [Accepted: 11/19/2023] [Indexed: 01/26/2024] Open
Abstract
BACKGROUND AND AIMS Research on the association between activity levels and sedentary behaviour with frailty in patients affected by hepatitis B cirrhosis is sparse. This study aimed to explore the association of frailty with activity levels and sedentary behaviours in patients with hepatitis B cirrhosis. DESIGN This cross-sectional study followed the STROBE checklist. METHODS This study was conducted in Guangzhou, China, between August 2021 and October 2022. The frailty condition of patients with hepatitis B cirrhosis was assessed using the liver frailty index (LFI). Their physical activity levels and sedentary time were assessed using the International Questionnaire of Physical Activity. Pearson correlation and binary logistic regression were used to analyse the data. RESULTS Among the 503 patients with hepatitis B cirrhosis in the final analysis, 107 (21.3%) were identified as frail. Frailty was negatively correlated with walking time (r = -0.174, p < 0.001), moderate-intensity activity time (r = -0.185, p < 0.001), high-intensity activity time (r = -0.243, p < 0.001) and total activity time (r = -0.256, p < 0.001). Patients with insufficient activity (<150 min/week) and sedentary behaviour (≥420 min/day) were found to have 2.829 times higher risk of frailty than those with sufficient activity (≥150 min/week) and no sedentary behaviour (<420 min/day) (95% CI: 1.380, 5.799). CONCLUSION Patients with hepatitis B cirrhosis who exhibited frailty demonstrated limited physical activity and engaged in sedentary behaviours. NO PATIENT OR PUBLIC CONTRIBUTION Patients with hepatitis B cirrhosis contributed their data to the study.
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Affiliation(s)
- Lili Li
- School of NursingSouthern Medical UniversityGuangzhouGuangdongChina
| | - Xia Fu
- Department of NursingThe Eighth Affiliated Hospital of Sun Yat‐sen UniversityShenzhenGuangdongChina
| | - Na He
- Department of Infectious DiseasesThe Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouGuangdongChina
| | - Weiqiang Gan
- Department of Infectious DiseasesThe Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouGuangdongChina
- Guangdong Key Laboratory of Liver Disease ResearchThe Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouGuangdongChina
| | - Yang Zhao
- School of NursingSouthern Medical UniversityGuangzhouGuangdongChina
| | - Ri‐hua Xie
- School of NursingSouthern Medical UniversityGuangzhouGuangdongChina
- Women and Children Medical Research Center, Department of NursingFoshan Women and Children HospitalFoshanGuangdongChina
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Orman ES, Desai AP. The PRIMER study: Nudging patients with liver disease toward healthier habits, one step at a time. Liver Transpl 2024; 30:1-3. [PMID: 37540171 PMCID: PMC10965141 DOI: 10.1097/lvt.0000000000000235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 07/31/2023] [Indexed: 08/05/2023]
Affiliation(s)
- Eric S Orman
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
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