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Development of a novel frailty index to predict mortality in patients with end‐stage liver disease
Open accessAbstract
Cirrhosis is characterized by muscle wasting, malnutrition, and functional decline that confer excess mortality not well quantified by the Model for End-Stage Liver Disease (MELD) Sodium (MELDNa) score. We aimed to develop a frailty index to capture these extrahepatic complications of cirrhosis and enhance mortality prediction in patients with cirrhosis. Consecutive outpatients listed for liver transplantation at a single transplant center without MELD exceptions were assessed with candidate frailty measures. Best subset selection analyses with Cox regression identified subsets of frailty measures that predicted waitlist mortality (=death or delisting because of sickness). We selected the frailty index by balancing statistical accuracy with clinical utility. The net reclassification index (NRI) evaluated the %patients correctly reclassified by adding the frailty index to MELDNa. Included were 536 patients with cirrhosis with median MELDNa of 18. One hundred seven (20%) died/were delisted. The final frailty index consisted of: grip strength, chair stands, and balance. The ability of MELDNa and the frailty index to correctly rank patients according to their 3-month waitlist mortality risk (i.e., concordance-statistic) was 0.80 and 0.76, respectively, but 0.82 for MELDNa+frailty index together. Compared with MELDNa alone, MELDNa+frailty index correctly reclassified 16% of deaths/delistings (P = 0.005) and 3% of nondeaths/delistings (P = 0.17) with a total NRI of 19% (P < 0.001). Compared to those with robust frailty index scores (<20th percentile), cirrhotics with poor frailty index scores (>80th percentile) were more impaired by gait speed, difficulty with Instrumental Activities of Daily Living, exhaustion, and low physical activity (P < 0.001 for each). CONCLUSION: Our frailty index for patients with cirrhosis, comprised of three performance-based metrics, has construct validity for the concept of frailty and improves risk prediction of waitlist mortality over MELDNa alone. (Hepatology 2017;66:564-574).
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“Finally, malnutrition [105], frailty [106, 107] and especially sarcopenia [108, 109, 110, 111] have become increasingly important in patients with advanced chronic liver disease and should be evaluated and treated in each patient.”
From Current treatment of non‐alcoholic fatty liver disease (2022) · cites this paper as [106]
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Self-citationReport from the American Society of Transplantation on frailty in solid organ transplantation
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BackgroundInfluentialSelf-citationLai, J. C., Rahimi, R. S., Verna, E. C., Kappus, M. R., Dunn, M. A., McAdams-DeMarco, M., Haugen, C. E., Volk, M. L., Duarte-Rojo, A., Ganger, D. R., et al. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.01.028 · Cited by 229
Self-citationDuarte‐Rojo, A., Ruiz‐Margáin, A., Montaño‐Loza, A. J., Macías‐Rodríguez, R. U., Ferrando, A., & Kim, W. R. (2018) · Liver Transplantation · doi:10.1002/lt.24958 · Cited by 221
“2B), allowing reclassification of 19% of patients with or without predicted death/delisting.((38)) These findings might have some practical implications, for instance, some patients with irreversible frailty might benefit from strategies to reduce the waiting time for LT, such as living donor related transplant or acc…”
BackgroundInfluentialReview article: malnutrition/sarcopenia and frailty in patients with cirrhosis
Bunchorntavakul, C., & Reddy, K. R. (2019) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.15571 · Cited by 230
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Self-citationPhysical frailty after liver transplantation
Lai, J. C., Segev, D. L., McCulloch, C. E., Covinsky, K. E., Dodge, J. L., & Feng, S. (2018) · American Journal of Transplantation · doi:10.1111/ajt.14675 · Cited by 165
Self-citationChanges in frailty are associated with waitlist mortality in patients with cirrhosis
Lai, J. C., Dodge, J. L., Kappus, M. R., Dunn, M. A., Volk, M. L., Duarte‐Rojo, A., Ganger, D. R., Rahimi, R. S., McCulloch, C. E., Haugen, C. E., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.03.029 · Cited by 160
“[1] Consisting of grip strength, chair stands, and balance testing, the LFI can predict mortality among patients with cirrhosis awaiting liver transplantation above and beyond traditional metrics of liver disease severity (such as the Model for EndStage Liver Disease (MELDNa) score or the presence of ascites / hepatic…”
BackgroundSelf-citationBuchard, B., Boirie, Y., Cassagnes, L., Lamblin, G., Coilly, A., & Abergel, A. (2020) · Nutrients · doi:10.3390/nu12010186 · Cited by 127
“[84] developed a new tool called the Liver Frailty Index (LFI) to assess frailty by combining grip strength, chair stands (CST) and balance tests (Appendix A Table A5).”
MethodPraktiknjo, M., Clees, C., Pigliacelli, A., Fischer, S., Jansen, C., Lehmann, J., Pohlmann, A., Lattanzi, B., Krabbe, V., Strassburg, C. P., et al. (2019) · Clinical and Translational Gastroenterology · doi:10.14309/ctg.0000000000000025 · Cited by 123
“A test battery to perform frailty assessment was not possible in this retrospective study (38).”
MethodFrailty in advanced liver disease
Laube, R., Wang, H., Park, L., Heyman, J. K., Vidot, H., Majumdar, A., Strasser, S. I., McCaughan, G. W., & Liu, K. (2018) · Liver International · doi:10.1111/liv.13917 · Cited by 124
Lai, J. C., Shui, A. M., Duarte‐Rojo, A., Ganger, D. R., Rahimi, R. S., Huang, C., Yao, F., Kappus, M. R., Boyarsky, B. J., McAdams‐DeMarco, M., et al. (2021) · Hepatology · doi:10.1002/hep.32268 · Cited by 119
“Natural differences in grip strength by sex are adjusted for in this calculation.[7] This index was developed specifically for patients with cirrhosis in the ambulatory setting.”
BackgroundSelf-citationThe Range and Reproducibility of the Liver Frailty Index
Wang, C. W., Lebsack, A. E., Chau, S., & Lai, J. C. (2019) · Liver Transplantation · doi:10.1002/lt.25449 · Cited by 114
“We aimed to (1) determine the range of LFI scores in adults with chronic liver disease but without cirrhosis, (2) determine the range of LFI scores in adults without known liver disease, and (3) evaluate reproducibility of the LFI in adults with cirrhosis listed for liver transplantation.”
BackgroundMethodInfluentialSelf-citationPhysical Function, Physical Activity, and Quality of Life After Liver Transplantation
Dunn, M. A., Rogal, S. S., Duarte‐Rojo, A., & Lai, J. C. (2020) · Liver Transplantation · doi:10.1002/lt.25742 · Cited by 114
“In 1 study of over 500 liver transplant candidates, frailty was measured using the LFI, which is a composite performance test including grip strength, timed chair stands, and balance testing that measures physical frailty on a continuous scale, with a strong predictive value in persons with cirrhosis.(5,6) Among ~200…”
MethodSelf-citationNutrition Support of Children With Chronic Liver Diseases
Mouzaki, M., Bronský, J., Gupte, G. L., Hojsak, I., Jahnel, J., Pai, N., Quirós‐Tejeira, R. E., Wieman, R., & Sundaram, S. S. (2019) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0000000000002443 · Cited by 112
“Modified measures of frailty (eg, frailty index: the combination of handgrip strength, chair stands, and balance) along with MELDNaþ outperform either measure alone in terms of predicting 3-month liver transplant wait list mortality in adults (16).”
MethodMeasuring frailty in younger populations: a rapid review of evidence
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Frailty is associated with increased risk of cirrhosis disease progression and death
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“These results not only confirm the prognostic relevance of the LFI for mortality in decompensated patients, which has been established through several recent publications,[4,5,28] but also add frailty to the prognostic toolkit in compensated disease, where predictive metrics are limited.”
BackgroundResultSelf-citationReview article: impact of exercise on physical frailty in patients with chronic liver disease
Williams, F. R., Berzigotti, A., Lord, J. M., Lai, J. C., & Armstrong, M. J. (2019) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.15491 · Cited by 109
Self-citationEASL Clinical Practice Guidelines on the management of cystic liver diseases
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Serum levels of prealbumin and albumin for preoperative risk stratification
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Acute‐on‐Chronic Liver Failure: Getting Ready for Prime Time?
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“(51) Brain dysfunction impacts endof-life decision-making and candidacy for LT.(37,52) MaNageMeNt oF INFeCtIoN IN aN eFFoRt to pReVeNt aClF Infections are one of the most important precipitants of ACLF based on Western definitions.”
BackgroundSelf-citationThe immense heterogeneity of frailty in neurosurgery: a systematic literature review
Pazniokas, J., Gandhi, C. D., Theriault, B. C., Schmidt, M. H., Cole, C. D., Al‐Mufti, F., Santarelli, J. G., & Bowers, C. A. (2020) · Neurosurgical Review · doi:10.1007/s10143-020-01241-2 · Cited by 98
Kardashian, A. A., Ge, J., McCulloch, C. E., Kappus, M. R., Dunn, M. A., Duarte‐Rojo, A., Volk, M. L., Rahimi, R. S., Verna, E. C., Ganger, D. R., et al. (2020) · Hepatology · doi:10.1002/hep.31406 · Cited by 97
“We have demonstrated that the Liver Frailty Index is strongly associated with mortality in patients with cirrhosis awaiting liver transplantation.(8,11-14) Furthermore, the Liver Frailty Index can capture the mortality associated with portal hypertensive complications, including ascites and encephalopathy, which can o…”
BackgroundMethodSelf-citationMulticenter Study of Age, Frailty, and Waitlist Mortality Among Liver Transplant Candidates
Haugen, C. E., McAdams‐DeMarco, M., Holscher, C. M., Ying, H., Gurakar, A. O., Garonzik‐Wang, J., Cameron, A. M., Segev, D. L., & Lai, J. C. (2019) · Annals of Surgery · doi:10.1097/sla.0000000000003207 · Cited by 95
“Frailty We studied the LFI as previously defined in liver transplant candidates.(11,14) The LFI is composed of 3 components that include grip strength, balance testing, and chair stands.”
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Self-citationPuri, P., Dhiman, R. K., Taneja, S., Tandon, P., Merli, M., Anand, A. C., Arora, A., Acharya, S. K., Benjamin, J., Chawla, Y. K., et al. (2020) · Journal of Clinical and Experimental Hepatology · doi:10.1016/j.jceh.2020.09.003 · Cited by 98
Lin, F., Visina, J., Bloomer, P. M., Dunn, M. A., Josbeno, D. A., Zhang, X., Clemente, A. P. G., Tevar, A. D., Hughes, C. B., Jakicic, J. M., et al. (2021) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000001376 · Cited by 91
“Using these metrics, nearly a quarter of patients with ESLD meet the criteria for frailty and experience increased mortality, hospitalizations, nonhome discharge, transplant waitlist attrition, and posttransplant complications (2,3,8,9).”
BackgroundMethodACG Clinical Guideline: Malnutrition and Nutritional Recommendations in Liver Disease
Singal, A. K., Wong, R. J., Dasarathy, S., Abdelmalek, M. F., Neuschwander‐Tetri, B. A., Limketkai, B. N., Petrey, J., & McClain, C. J. (2025) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000003379 · Cited by 93
“Among candidates awaiting LT, subjects with cirrhosis and with frailty are more likely to experience waitlist mortality (122) and in-hospital mortality (123).”
The evolution and impact of sarcopenia pre‐ and post‐liver transplantation
Bhanji, R. A., Takahashi, N., Moynagh, M. R., Narayanan, P., Angirekula, M., Mara, K. C., Dierkhising, R., & Watt, K. D. S. (2019) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.15161 · Cited by 82
“Functional measures can be associated with prognosis and in an attempt to capture these, the liver frailty index was developed in patients with end‐stage liver disease awaiting liver transplant.(18) This index was used to assess frailty following liver transplant in one study and showed worsening frailty in the first…”
MethodRomán, E., Nieto, J. C., Gely, C., Vidal, S., Pozuelo, M., Poca, M., Juárez, C., Guarner, C., Manichanh, C., & Soriano, G. (2019) · Hepatology Communications · doi:10.1002/hep4.1325 · Cited by 80
“(10) Moreover, individuals with previous falls are frequently predisposed to recurrent falling,(7,8,11) thus supporting the growing concept of frailty in patients with cirrhosis(12) and the need for preventive measures.”
BackgroundNovel perspectives in the management of decompensated cirrhosis
Bernardi, M., & Caraceni, P. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0045-2 · Cited by 81
Fatty Liver Disease: Diagnosis and Stratification
Saiman, Y., Duarte‐Rojo, A., & Rinella, M. E. (2021) · Annual Review of Medicine · doi:10.1146/annurev-med-042220-020407 · Cited by 78
Myostatin and beyond in cirrhosis: all roads lead to sarcopenia
Dasarathy, S. (2017) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12262 · Cited by 77
“recognized as an independent adverse prognostic indicator in cirrhosis.(53,54) Even though contractile function and muscle”
BackgroundTapper, E. B., Baki, J., Parikh, N. D., & Lok, A. S.-F. (2018) · Hepatology · doi:10.1002/hep.30336 · Cited by 74
“Frail performance was defined with respect to sex and body mass index (Supporting Methods).(16) The number of chair-stands (repeatedly rising from a seated position to standing and sitting again) performed within 30 seconds was also assessed.”
BackgroundMethodInfluentialHanai, T., Shiraki, M., Imai, K., Suetsugu, A., Takai, K., Moriwaki, H., & Shimizu, M. (2019) · Hepatology Research · doi:10.1111/hepr.13420 · Cited by 75
Hernández‐Conde, M., Llop, E., Gómez-Pimpollo, L., Fernández‐Carrillo, C., Luis, R., den Brule, E. V., Perelló, C., López-Gómez, M., Abad, J., Porras, J. L. M., et al. (2021) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000001301 · Cited by 74
“The Liver Frailty Index is a simple test that can be feasibly performed in the outpatient setting at baseline and be followed over time (11).”
BackgroundMELD‐GRAIL‐Na: Glomerular Filtration Rate and Mortality on Liver‐Transplant Waiting List
Asrani, S. K., Jennings, L. W., Kim, W. R., Kamath, P. S., Levitsky, J., Nadim, M. K., Testa, G., Leise, M. D., Trotter, J. F., & Klintmalm, G. B. (2019) · Hepatology · doi:10.1002/hep.30932 · Cited by 75
“Among patients with high MELD-Na scores, extrahepatic factors such as infection may play a role in diminishing the model’s performance.(25-27) Hence, reliance of any singular predictive model may be fraught by the influence of other drivers of mortality.”
BackgroundCola, S. D., D’Amico, G., Caraceni, P., Schepis, F., Loredana, S., Lampertico, P., Toniutto, P., Martini, S., Maimone, S., Colecchia, A., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.05.020 · Cited by 72
Lai, J. C., Dodge, J. L., Kappus, M. R., Wong, R. J., Mohamad, Y., Segev, D. L., & McAdams‐DeMarco, M. (2020) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000001113 · Cited by 71
Self-citationNutrition and the transplant candidate
Mazurak, V. C., Tandon, P., & Montaño‐Loza, A. J. (2017) · Liver Transplantation · doi:10.1002/lt.24848 · Cited by 72
“Tests of physical frailty that include performance measures such as chair stands and balance as well as self-reported measures of daily activity and unplanned weight loss also correlate with poor clinical outcomes in cirrhosis, including hospitalization and death.((58,59))”
BackgroundWilliams, F. R., Milliken, D., Lai, J. C., & Armstrong, M. J. (2021) · Hepatology Communications · doi:10.1002/hep4.1688 · Cited by 69
Self-citationLiver transplantation in the patient with physical frailty
Tandon, P., Zanetto, A., Piano, S. S., Heimbach, J. K., & Dasarathy, S. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.03.025 · Cited by 64
AGA Clinical Practice Update on Palliative Care Management in Cirrhosis: Expert Review
Tandon, P., Walling, A. M., Patton, H. M., & Taddei, T. H. (2020) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2020.11.027 · Cited by 63
Couteur, D. G. L., Ngu, M., Hunt, N. J., Brandon, A. E., Simpson, S. J., & Cogger, V. C. (2025) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-025-01099-z · Cited by 73
“…index was found to predict — better than age or the model for end-stage liver disease score — waitlist mortality as well as post-transplantation mortality, hepatic decompensation, duration of hospitalizations, health-related quality of life and physical function after transplantation 140,141 .”
Duarte‐Rojo, A., Bloomer, P. M., Rogers, R. J., Hassan, M. A. S., Dunn, M. A., Tevar, A. D., Vivis, S. L., Bataller, R. A., Hughes, C. B., Ferrando, A. A., et al. (2020) · Liver Transplantation · doi:10.1002/lt.25950 · Cited by 62
“(1,2) Physical decline leading to frailty has been increasingly recognized as a key driving factor for waitlist removal along with liver failure.(3,4) Frailty is present in 18% to 25% of patients with end-stage liver disease (ESLD), and it is associated with nearly twice the mortality of reference populations as well…”
BackgroundMethodInfluentialPalliative care in end‐stage liver disease: Time to do better?
Mazzarelli, C., Prentice, W. M., Heneghan, M. A., Belli, L. S., Agarwal, K., & Cannon, M. D. (2018) · Liver Transplantation · doi:10.1002/lt.25193 · Cited by 63
“Recently, the combination of a novel frailty index with modified Model for End-Stage Liver Disease score that includes serum sodium (MELDNa) score has been shown to be a better predictor of wait-list mortality compared with MELD-Na alone.((37)) The CLIF-C acute-on-chronic liver failure (ACLF) score has been validated…”
MethodAssociation Between Liver Transplant Wait-list Mortality and Frailty Based on Body Mass Index
Haugen, C. E., McAdams‐DeMarco, M., Verna, E. C., Rahimi, R. S., Kappus, M. R., Dunn, M. A., Volk, M. L., Gurakar, A. O., Duarte‐Rojo, A., Ganger, D. R., et al. (2019) · JAMA Surgery · doi:10.1001/jamasurg.2019.2845 · Cited by 60
“The mean (SD) MELDNa score was 18 (6), and 290 candidates (26.”
BackgroundSelf-citationChanging Trends in Liver Transplantation: Challenges and Solutions
Ivanics, T., Abreu, P., Martin, E. D., & Sapisochín, G. (2020) · Transplantation · doi:10.1097/tp.0000000000003454 · Cited by 62
“These MELD “exceptions” include refractory ascites, hepatopulmonary syndrome, portopulmonary hypertension, and refractory pruritus(183) as well as nonstandardized MELD exceptions such as female gender, hypoalbuminemia, and frailty.(184,185) Management of patients with low MELD is a challenge as there is no way to pred…”
BackgroundFalls are common, morbid, and predictable in patients with cirrhosis
Tapper, E. B., Nikirk, S. J., Parikh, N. D., & Zhao, L. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.04.012 · Cited by 59
Hepatic encephalopathy impacts the predictive value of the Fried Frailty Index
Tapper, E. B., Konerman, M. A., Murphy, S. L., & Sonnenday, C. J. (2018) · American Journal of Transplantation · doi:10.1111/ajt.15020 · Cited by 59
Kuo, S. Z., Ahmad, M., Dunn, M. A., Montaño‐Loza, A. J., Carey, E. J., Lin, S., Moghe, A., Chen, H.-W., Ebadi, M., & Lai, J. C. (2019) · Transplantation · doi:10.1097/tp.0000000000002741 · Cited by 58
“4 Coronary artery disease 5 (4) 4 (5) 1 (2) 0.”
Self-citationWan, S., Nie, Y., Zhang, Y., Liu, C., & Zhu, X. (2020) · Disease Markers · doi:10.1155/2020/5193028 · Cited by 57
RetractedCardona, M., Lewis, E., Kristensen, M. R., Skjøt‐Arkil, H., Ekmann, A., Nygaard, H. H., Jensen, J. J., Jensen, R. O., Pedersen, J. L., Turner, R. M., et al. (2018) · European Geriatric Medicine · doi:10.1007/s41999-018-0123-6 · Cited by 56
Ge, J., Kim, W. R., Lai, J. C., & Kwong, A. J. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.03.003 · Cited by 60
Self-citationClayton‐Chubb, D., Kemp, W. W., Majeed, A., Lubel, J. S., Woods, R. L., Tran, C., Ryan, J. L., Hodge, A. D., Schneider, H. G., McNeil, J. J., et al. (2023) · Liver International · doi:10.1111/liv.15725 · Cited by 61
Rodríguez‐Perálvarez, M., Gómez‐Bravo, M. Á., Sánchez‐Antolín, G., de la Rosa, G., Bilbao, I., & Colmenero, J. (2020) · Transplantation · doi:10.1097/tp.0000000000003281 · Cited by 54
Relationship between Osteosarcopenia and Frailty in Patients with Chronic Liver Disease
Saeki, C., Kanai, T., Nakano, M., Oikawa, T., Torisu, Y., Abo, M., Saruta, M., & Tsubota, A. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9082381 · Cited by 54
A Critical Review of MELD as a Reliable Tool for Transplant Prioritization
Sacleux, S., & Samuel, D. (2019) · Seminars in Liver Disease · doi:10.1055/s-0039-1688750 · Cited by 53
Cachexia is Prevalent in Patients With Hepatocellular Carcinoma and Associated With Worse Prognosis
Rich, N. E., Phen, S., Desai, N., Mittal, S., Yopp, A. C., Yang, J. D., Marrero, J. A., Iyengar, P., Infante, R. E., & Singal, A. G. (2021) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2021.09.022 · Cited by 52
Bittermann, T., Dwinnells, K., Chadha, S., Wolf, M. S., Olthoff, K. M., & Serper, M. (2020) · Liver Transplantation · doi:10.1002/lt.25830 · Cited by 50
“(17) Future research should investigate how the Liver Frailty Index is associated with HL and outcomes.(43) In conclusion, low HL was highly prevalent and associated with increased physical frailty and lower likelihood LT wait-listing in ESLD independent of HE, educational attainment, and other clinical and socioecono…”
Kahn, J., Wagner, D., Homfeld, N., Müller, H., Kniepeiss, D., & Schemmer, P. (2018) · Clinical Transplantation · doi:10.1111/ctr.13226 · Cited by 49
Management of diabetes mellitus in patients with cirrhosis: An overview and joint statement
Boursier, J., Anty, R., Carette, C., Cariou, B., Castéra, L., Caussy, C., Fontaine, H., Garioud, A., Gourdy, P., Guerci, B., et al. (2021) · Diabetes & Metabolism · doi:10.1016/j.diabet.2021.101272 · Cited by 51
Lai, J. C., Dodge, J. L., McCulloch, C. E., Covinsky, K. E., & Singer, J. P. (2019) · Hepatology Communications · doi:10.1002/hep4.1444 · Cited by 49
“Consisting purely of performance-based tests, the LFI enhances risk prediction above and beyond traditional, well-known predictors of mortality in patients with cirrhosis, including the Model for End-Stage Liver Disease ascites–sodium (MELD-Na), hepatic encephalopathy, and age.(3-5) Although the three components of th…”
BackgroundMethodInfluentialSelf-citationLiver Cirrhosis and Sarcopenia from the Viewpoint of Dysbiosis
Nishikawa, H., Enomoto, H., Nishiguchi, S., & Iijima, H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21155254 · Cited by 49
“In LC patients, sarcopenia, which is defined by decline in muscle mass and strength and/or physical activity, can occur because the excessive consumption of BCAAs makes it difficult to synthesize the protein required for muscle mass increase [20].”
BackgroundInfluentialBurra, P., Samuel, D., Sundaram, V., Duvoux, C., Petrowsky, H., Terrault, N. A., & Jalan, R. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.01.007 · Cited by 48
“Examples are the Sodium MELD [11], the composition of Sodium MELD and frailty index [12], the MELD and sarcopenia score [10, 13], which seems to outperform MELD notably in patients with MELD <15 [13].”
MethodNey, M., Tangri, N., Dobbs, B., Bajaj, J. S., Rolfson, D. B., Ma, M. M., Ferguson, T. W., Bhardwaj, P., Bailey, R. J., Abraldeṣ, J. G., et al. (2018) · The American Journal of Gastroenterology · doi:10.1038/s41395-018-0243-0 · Cited by 46
“[64] to assess the impact of therapeutic interventions.”
BackgroundA Comparison of Different Frailty Scores and Impact of Frailty on Outcome in Patients With Cirrhosis
Singh, S., Taneja, S., Tandon, P., Bansal, A., Gorsi, U., Roy, A., De, A., Verma, N., Premkumar, M., Duseja, A. K., et al. (2021) · Journal of Clinical and Experimental Hepatology · doi:10.1016/j.jceh.2021.07.003 · Cited by 46
Cullaro, G., Park, M., & Lai, J. C. (2018) · Hepatology · doi:10.1002/hep.30058 · Cited by 45
“These patients were enrolled as part of a prospective study of adults ( 18 years) with cirrhosis who were seen as outpatients in the UCSF Liver Transplant Clinics.((18,19)) Patients with severe hepatic encephalopathy, as defined by the time to complete a numbers connection test((20)) of >120 seconds, were excluded bec…”
InfluentialSelf-citationTranslation of the Frailty Paradigm from Older Adults to Children with Cardiac Disease
Panchangam, C., White, D. A., Goudar, S., Birnbaum, B. F., Malloy-Walton, L. E., Gross‐Toalson, J., Reid, K. J., Shirali, G. S., & Parthiban, A. (2020) · Pediatric Cardiology · doi:10.1007/s00246-020-02354-7 · Cited by 45
Frailty in inflammatory bowel diseases: an emerging concept
Kochar, B. D., Orkaby, A. R., Ananthakrishnan, A. N., & Ritchie, C. S. (2021) · Therapeutic Advances in Gastroenterology · doi:10.1177/17562848211025474 · Cited by 45
Thuluvath, P. J., Hanish, S. I., & Savva, Y. (2018) · Transplantation · doi:10.1097/tp.0000000000002355 · Cited by 44
Association between sarcopenia and osteoporosis in chronic liver disease
Hayashi, M., Abe, K., Fujita, M., Okai, K., Takahashi, A., & Ohira, H. (2018) · Hepatology Research · doi:10.1111/hepr.13192 · Cited by 43
Siramolpiwat, S., Limthanetkul, N., Pornthisarn, B., Vilaichone, R., Chonprasertsuk, S., Bhanthumkomol, P., Nunanan, P., & Issariyakulkarn, N. (2023) · BMC Gastroenterology · doi:10.1186/s12876-023-02789-1 · Cited by 42
“Frailty assessment Frailty was assessed by LFI, which consists of the following 3 performance-based tests: (1) Grip strength: the average of 3 trials, measured in the subject’s dominant hand using a hand dynamometer (CAMRY digital hand dynamometer EH101); (2) Timed chair stands: measured as the number of seconds it ta…”
MethodSarcopenia in nonalcoholic fatty liver disease: new challenges for clinical practice
Sherif, O. E., Dhaliwal, A., Newsome, P. N., & Armstrong, M. J. (2020) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2020.1731303 · Cited by 40
Kremer, W. M., Nagel, M. C., Reuter, M., Hilscher, M., Michel, M. S., Kaps, L., Labenz, J., Galle, P. R., Sprinzl, M. F., Wörns, M., et al. (2020) · Clinical and Translational Gastroenterology · doi:10.14309/ctg.0000000000000211 · Cited by 43
“(20), frailty defined by the more complex Liver Frailty Index was independently associated with highermortality in these patients.”
BackgroundNutritional therapy for hepatocellular carcinoma
Ruiz‐Margáin, A., Román-Calleja, B. M., Moreno-Guillén, P., González-Regueiro, J. A., Kúsulas-Delint, D., Campos-Murguía, A., Flores-García, N. C., & Macías‐Rodríguez, R. U. (2021) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v13.i10.1440 · Cited by 42
Effects of In-Hospital Exercise on Frailty in Patients with Hepatocellular Carcinoma
Tsuchihashi, J., Koya, S., Hirota, K., Koga, N., Narao, H., Tomita, M., Kawaguchi, T., Hashida, R., Nakano, D., Tsutsumi, T., et al. (2021) · Cancers · doi:10.3390/cancers13020194 · Cited by 40
Sarcopenia and Frailty in Liver Cirrhosis
Nishikawa, H., Fukunishi, S., Asai, A., Nishiguchi, S., & Higuchi, K. (2021) · Life · doi:10.3390/life11050399 · Cited by 47
“The Liver Frailty Index (LFI) is a diagnostic method of frailty specific to liver diseases [79].”
MethodOlumba, F. C., Zhou, F., Park, Y., Chapman, W. C., & RESTORE Investigators Group (2023) · Journal of the American College of Surgeons · doi:10.1097/xcs.0000000000000555 · Cited by 41
The operationalization of fatigue in frailty scales: a systematic review
Knoop, V., Costenoble, A., Azzopardi, R. V., Vermeiren, S., Debain, A., Jansen, B., Scafoglieri, A., Bautmans, I., Bautmans, I., Verté, D., et al. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100911 · Cited by 40
Hirota, K., Kawaguchi, T., Koya, S., Nagamatsu, A., Tomita, M., Hashida, R., Nakano, D., Niizeki, T., Matsuse, H., Shiba, N. N., et al. (2019) · Hepatology Research · doi:10.1111/hepr.13453 · Cited by 39
Frailty and Sarcopenia in Patients Pre– and Post–Liver Transplant
Saiman, Y., & Serper, M. (2020) · Clinics in Liver Disease · doi:10.1016/j.cld.2020.08.004 · Cited by 41
Fozouni, L., Mohamad, Y., Lebsack, A. E., Freise, C. E., Stock, P. G., & Lai, J. C. (2019) · Liver Transplantation · doi:10.1002/lt.25669 · Cited by 38
“Only 1 nonfrail patient was treated for an active CMV infection within 3 months after LT.”
BackgroundMethodInfluentialSelf-citationLattanzi, B., Bruni, A., Cola, S. D., Molfino, A., Santis, A. D., Muscaritoli, M., & Merli, M. (2021) · Nutrients · doi:10.3390/nu13072296 · Cited by 38
Frailty measurement in research and clinical practice: An updated review
Dent, E., Hanlon, P., Kowal, P. R., & Hoogendijk, E. O. (2025) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2025.106595 · Cited by 42
Meena, B. L., Taneja, S., Tandon, P., Sahni, N., Soundararajan, R., Gorsi, U., De, A., Verma, N., Premkumar, M., Duseja, A., et al. (2023) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.16035 · Cited by 36
Rana, A. A., Witte, E. D., Halazun, K. J., Sood, G., Mindikoglu, A. L., Sussman, N., Vierling, J. M., Kueht, M. L., Galván, N. T. N., Cotton, R. T., et al. (2017) · Clinical Transplantation · doi:10.1111/ctr.13141 · Cited by 36
“The same can be stated about serum sodium, serum albumin, recipient age, renal failure, the MELD score, and frailty[4, 79, 17, 18].”
BackgroundFrailty as Tested by Gait Speed Is a Risk Factor for Liver Transplant Respiratory Complications
Salim, T. I., Nestlerode, L. C., Lucatorto, E., Wasserman‐Wincko, T., Din, H. A., Landsittel, D. P., Tevar, A. D., Johnson, J. T., Duarte‐Rojo, A., & Dunn, M. A. (2020) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000000609 · Cited by 36
Frailty and solid-organ transplant candidates: a scoping review
Kao, J., Reid, N., Hubbard, R. E., Homes, R., Hanjani, L. S., Pearson, E., Logan, B., King, S. J., Fox, S. T., & Gordon, E. H. (2022) · BMC Geriatrics · doi:10.1186/s12877-022-03485-7 · Cited by 37
“Developed only four years ago, it comprises three performance-based tests (of grip strength, sit-to-stand transfers and balance) and was originally designed to capture extrahepatic complications of cirrhosis and to enhance mortality prediction in patients with cirrhosis [64].”
BackgroundMarrone, G., Serra, A., Miele, L., Biolato, M., Liguori, A., Grieco, A., & Gasbarrini, A. (2023) · World Journal of Gastroenterology · doi:10.3748/wjg.v29.i19.2905 · Cited by 35
Metadata
- Authors
- Lai, J. C., Covinsky, K. E., Dodge, J. L., Boscardin, W. J., Segev, D. L., Roberts, J. P., & Feng, S.
- Affiliations
- University of California, San Francisco (US)
- Johns Hopkins University (US)
- Corresponding author
- Lai, Jennifer C.
- ORCID
- Venue
- Hepatology
- Published
- 2017-06-28
- Volume
- 66
- Issue
- 2
- Pages
- 564-574
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- PMC
- PMC5519430
- OpenAlex
- W2606209221
- Cited by
- 556
- References
- 34
- Citations by year
- 2026: 75 · 2025: 62 · 2024: 71 · 2023: 62 · 2022: 50 · 2021: 69 · 2020: 60 · 2019: 59 · 2018: 35 · 2017: 10
- FWCI
- 27.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- American College of Gastroenterology (K23AG048337, P30 DK026743, P30AG044281)
- National Institutes of Health
- University of California, San Francisco (P30 AG044281, P30DK026743)
- National Institute on Aging (K23AG048337, R01AG042504, R03AG045072, P30AG044281)
- National Institute of Diabetes and Digestive and Kidney Diseases (K24DK101828, P30DK026743)
- Liver Center, University of California, San Francisco (P30 DK026743, DK026743)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Keywords
- frailty index, end-stage liver disease, liver cirrhosis, waitlist mortality, MELD-Na, liver transplantation, mortality prediction, grip strength, chair stand, balance, net reclassification improvement, instrumental activities of daily living, walking speed, exhaustion, physical activity
- MeSH terms
- Activities of Daily Living, Cause of Death, Disability Evaluation, Female, Humans, Liver Cirrhosis, Male, Middle Aged, Physical Fitness, Predictive Value of Tests, Prognosis, Retrospective Studies, Severity of Illness Index, Waiting Lists, Reproducibility of Results, Cohort Studies, Survival Rate, Liver Transplantation, Databases, Factual, Risk Assessment, End Stage Liver Disease
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