A rapid, non-invasive, clinical surveillance for CachExia, sarcopenia, portal hypertension, and hepatocellular carcinoma in end-stage liver disease: the ACCESS-ESLD study protocol.
Abbreviated MRI
Biomarkers
Hepatocellular carcinoma
Liver cirrhosis
Portal hypertension
Sarcopenia
Journal
BMC gastroenterology
ISSN: 1471-230X
Titre abrégé: BMC Gastroenterol
Pays: England
ID NLM: 100968547
Informations de publication
Date de publication:
21 Dec 2023
21 Dec 2023
Historique:
received:
24
08
2023
accepted:
13
12
2023
medline:
22
12
2023
pubmed:
22
12
2023
entrez:
22
12
2023
Statut:
epublish
Résumé
Liver cirrhosis, the advanced stage of many chronic liver diseases, is associated with escalated risks of liver-related complications like decompensation and hepatocellular carcinoma (HCC). Morbidity and mortality in cirrhosis patients are linked to portal hypertension, sarcopenia, and hepatocellular carcinoma. Although conventional cirrhosis management centered on treating complications, contemporary approaches prioritize preemptive measures. This study aims to formulate novel blood- and imaging-centric methodologies for monitoring liver cirrhosis patients. In this prospective study, 150 liver cirrhosis patients will be enrolled from three Swedish liver clinics. Their conditions will be assessed through extensive blood-based markers and magnetic resonance imaging (MRI). The MRI protocol encompasses body composition profile with Muscle Assement Score, portal flow assessment, magnet resonance elastography, and a abbreviated MRI for HCC screening. Evaluation of lifestyle, muscular strength, physical performance, body composition, and quality of life will be conducted. Additionally, DNA, serum, and plasma biobanking will facilitate future investigations. The anticipated outcomes involve the identification and validation of non-invasive blood- and imaging-oriented biomarkers, enhancing the care paradigm for liver cirrhosis patients. Notably, the temporal evolution of these biomarkers will be crucial for understanding dynamic changes. Clinicaltrials.gov, registration identifier NCT05502198. Registered on 16 August 2022. Link: https://classic. gov/ct2/show/NCT05502198 .
Sections du résumé
BACKGROUND
BACKGROUND
Liver cirrhosis, the advanced stage of many chronic liver diseases, is associated with escalated risks of liver-related complications like decompensation and hepatocellular carcinoma (HCC). Morbidity and mortality in cirrhosis patients are linked to portal hypertension, sarcopenia, and hepatocellular carcinoma. Although conventional cirrhosis management centered on treating complications, contemporary approaches prioritize preemptive measures. This study aims to formulate novel blood- and imaging-centric methodologies for monitoring liver cirrhosis patients.
METHODS
METHODS
In this prospective study, 150 liver cirrhosis patients will be enrolled from three Swedish liver clinics. Their conditions will be assessed through extensive blood-based markers and magnetic resonance imaging (MRI). The MRI protocol encompasses body composition profile with Muscle Assement Score, portal flow assessment, magnet resonance elastography, and a abbreviated MRI for HCC screening. Evaluation of lifestyle, muscular strength, physical performance, body composition, and quality of life will be conducted. Additionally, DNA, serum, and plasma biobanking will facilitate future investigations.
DISCUSSION
CONCLUSIONS
The anticipated outcomes involve the identification and validation of non-invasive blood- and imaging-oriented biomarkers, enhancing the care paradigm for liver cirrhosis patients. Notably, the temporal evolution of these biomarkers will be crucial for understanding dynamic changes.
TRIAL REGISTRATION
BACKGROUND
Clinicaltrials.gov, registration identifier NCT05502198. Registered on 16 August 2022. Link: https://classic.
CLINICALTRIALS
RESULTS
gov/ct2/show/NCT05502198 .
Identifiants
pubmed: 38129794
doi: 10.1186/s12876-023-03093-8
pii: 10.1186/s12876-023-03093-8
doi:
Banques de données
ClinicalTrials.gov
['NCT05502198']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
454Informations de copyright
© 2023. The Author(s).
Références
Mokdad AA, Lopez AD, Shahraz S, Lozano R, Mokdad AH, Stanaway J, Murray CJ, et al. Liver cirrhosis mortality in 187 countries between 1980 and 2010: a systematic analysis. BMC Med. 2014;12:145.
pubmed: 25242656
pmcid: 4169640
doi: 10.1186/s12916-014-0145-y
Asrani SK, Devarbhavi H, Eaton J, Kamath PS. Burden of liver diseases in the world. J Hepatol. 2019;70:151–71.
pubmed: 30266282
doi: 10.1016/j.jhep.2018.09.014
Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis. Lancet. 2014;383:1749–61.
pubmed: 24480518
doi: 10.1016/S0140-6736(14)60121-5
García-Pagán J-C, Gracia-Sancho J, Bosch J. Functional aspects on the pathophysiology of portal hypertension in cirrhosis. J Hepatol. 2012;57:458–61.
pubmed: 22504334
doi: 10.1016/j.jhep.2012.03.007
Palaniyappan N, Cox E, Bradley C, Scott R, Austin A, O’Neill R, Ramjas G, et al. Non-invasive assessment of portal hypertension using quantitative magnetic resonance imaging. J Hepatol. 2016;65:1131–9.
pubmed: 27475617
pmcid: 5123896
doi: 10.1016/j.jhep.2016.07.021
Yoo J, Kim SW, Lee DH, Bae JS, Cho EJ. Prognostic role of spleen volume measurement using computed tomography in patients with compensated chronic liver disease from hepatitis B viral infection. Eur Radiol. 2021;31:1432–42.
pubmed: 32880698
doi: 10.1007/s00330-020-07209-6
Villanueva A. Hepatocellular Carcinoma. N Engl J Med. 2019;380:1450–62.
pubmed: 30970190
doi: 10.1056/NEJMra1713263
Galle PR, Forner A, Llovet JM, Mazzaferro V, Piscaglia F, Raoul J-L, Schirmacher P, et al. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69:182–236.
doi: 10.1016/j.jhep.2018.03.019
Park HJ, Jang HY, Kim SY, Lee SJ, Won HJ, Byun JH, Choi SH, et al. Non-enhanced magnetic resonance imaging as a surveillance tool for hepatocellular carcinoma: comparison with ultrasound. J Hepatol. 2020;72:718–24.
pubmed: 31836549
doi: 10.1016/j.jhep.2019.12.001
Gupta P, Soundararajan R, Patel A, Kumar-M P, Sharma V, Kalra N. Abbreviated MRI for hepatocellular carcinoma screening: a systematic review and meta-analysis. J Hepatol. 2021;75:108–19.
pubmed: 33548385
doi: 10.1016/j.jhep.2021.01.041
Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, Cooper C, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48:16–31.
pubmed: 30312372
doi: 10.1093/ageing/afy169
Tandon P, Ney M, Irwin I, Ma MM, Gramlich L, Bain VG, Esfandiari N, et al. Severe muscle depletion in patients on the liver transplant wait list: its prevalence and independent prognostic value. Liver Transpl. 2012;18:1209–16.
pubmed: 22740290
doi: 10.1002/lt.23495
Montano-Loza AJ, Meza-Junco J, Prado CM, Lieffers JR, Baracos VE, Bain VG, Sawyer MB. Muscle wasting is associated with mortality in patients with cirrhosis. Clin Gastroenterol Hepatol. 2012;10(166–173):e161.
Lai JC, Tandon P, Bernal W, Tapper EB, Ekong U, Dasarathy S, Carey EJ. Malnutrition, frailty, and sarcopenia in patients with cirrhosis: 2021 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021;74:1611–44.
pubmed: 34233031
doi: 10.1002/hep.32049
Linge J, Heymsfield SB, Dahlqvist LO. On the definition of sarcopenia in the presence of aging and obesity—initial Results from UK biobank. J Gerontol A. 2020;75:1309–16.
doi: 10.1093/gerona/glz229
Linge J, Ekstedt M, Dahlqvist LO. Adverse muscle composition is linked to poor functional performance and metabolic comorbidities in NAFLD. JHEP Rep. 2021;3:100197.
pubmed: 33598647
doi: 10.1016/j.jhepr.2020.100197
Linge J, Ekstedt M, Dahlqvist Leinhard O. Adverse muscle composition is linked to poor functional performance and metabolic comorbidities in NAFLD. JHEP Rep. 2020;3(1):100197. https://doi.org/10.1016/j.jhepr.2020.100197 .
(EMA) EMA. ICH E6 (R2) good clinical practice. 2016 In. https://www.ema.europa.eu/en/ich-e6-r2-good-clinical-practice .
Dasarathy S, Merli M. Sarcopenia from mechanism to diagnosis and treatment in liver disease. J Hepatol. 2016;65:1232–44.
pubmed: 27515775
pmcid: 5116259
doi: 10.1016/j.jhep.2016.07.040
Hanai T, Shiraki M, Ohnishi S, Miyazaki T, Ideta T, Kochi T, Imai K, et al. Rapid skeletal muscle wasting predicts worse survival in patients with liver cirrhosis. Hepatol Res. 2016;46:743–51.
pubmed: 26579878
doi: 10.1111/hepr.12616
West J, Romu T, Thorell S, Lindblom H, Berin E, Holm A-CS, Åstrand LL, et al. Precision of MRI-based body composition measurements of postmenopausal women. PLoS One. 2018;13:e0192495.
pubmed: 29415060
pmcid: 5802932
doi: 10.1371/journal.pone.0192495
Middleton MS, Haufe W, Hooker J, Borga M, Dahlqvist Leinhard O, Romu T, Tunón P, et al. Quantifying abdominal adipose tissue and thigh muscle volume and hepatic proton density fat fraction: repeatability and accuracy of an MR imaging–based, semiautomated analysis method. Radiology. 2017;283:438–49.
pubmed: 28278002
doi: 10.1148/radiol.2017160606
Campagna F, Montagnese S, Ridola L, Senzolo M, Schiff S, De Rui M, Pasquale C, et al. The animal naming test: an easy tool for the assessment of hepatic encephalopathy. Hepatology. 2017;66:198–208.
pubmed: 28271528
doi: 10.1002/hep.29146
Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, Bonsel G, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20:1727–36.
pubmed: 21479777
pmcid: 3220807
doi: 10.1007/s11136-011-9903-x
Loria A, Escheik C, Gerber NL, Younossi ZM. Quality of life in cirrhosis. Curr Gastroenterol Rep. 2013;15:1–7.
doi: 10.1007/s11894-012-0301-5
Younossi ZM, Guyatt G, Kiwi M, Boparai N, King D. Development of a disease specific questionnaire to measure health related quality of life in patients with chronic liver disease. Gut. 1999;45:295–300.
pubmed: 10403745
pmcid: 1727607
doi: 10.1136/gut.45.2.295
Hjortswang H, Järnerot G, Curman B, Sandberg-Gertzén H, Tysk C, Blomberg B, Almer S, et al. The short health scale: a valid measure of subjective health in ulcerative colitis. Scand J Gastroenterol. 2006;41:1196–203.
pubmed: 16990205
doi: 10.1080/00365520600610618
Krarup AL, Peterson E, Ringström G, Törnblom H, Hjortswang H, Simrén M. The short health scale. J Clin Gastroenterol. 2015;49:565–70.
pubmed: 25216385
doi: 10.1097/MCG.0000000000000209
Stjernman H, Grännö C, Järnerot G, Ockander L, Tysk C, Blomberg B, Ström M, et al. Short health scale: a valid, reliable, and responsive instrument for subjective health assessment in Crohn’s disease. Inflamm Bowel Dis. 2008;14:47–52.
pubmed: 17828783
doi: 10.1002/ibd.20255
Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, Scherr PA, et al. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol. 1994;49:M85–94.
pubmed: 8126356
doi: 10.1093/geronj/49.2.M85
Norman K, Stobäus N, Gonzalez MC, Schulzke J-D, Pirlich M. Hand grip strength: outcome predictor and marker of nutritional status. Clin Nutr. 2011;30:135–42.
pubmed: 21035927
doi: 10.1016/j.clnu.2010.09.010
Rantanen T, Guralnik JM, Foley D, Masaki K, Leveille S, Curb JD, White L. Midlife hand grip strength as a predictor of old age disability. Jama. 1999;281:558–60.
pubmed: 10022113
doi: 10.1001/jama.281.6.558
Wang CW, Feng S, Covinsky KE, Hayssen H, Zhou L-Q, Yeh BM, Lai JC. A comparison of muscle function, mass, and quality in liver transplant candidates: results from the functional assessment in liver transplantation (FrAILT) study. Transplantation. 2016;100:1692.
pubmed: 27314169
pmcid: 4962324
doi: 10.1097/TP.0000000000001232
Sasso M, Beaugrand M, De Ledinghen V, Douvin C, Marcellin P, Poupon R, Sandrin L, et al. Controlled attenuation parameter (CAP): a novel VCTE™ guided ultrasonic attenuation measurement for the evaluation of hepatic steatosis: preliminary study and validation in a cohort of patients with chronic liver disease from various causes. Ultrasound Med Biol. 2010;36:1825–35.
pubmed: 20870345
doi: 10.1016/j.ultrasmedbio.2010.07.005
West J, Dahlqvist Leinhard O, Romu T, Collins R, Garratt S, Bell JD, Borga M, et al. Feasibility of MR-based body composition analysis in large scale population studies. PLoS One. 2016;11:e0163332.
pubmed: 27662190
pmcid: 5035023
doi: 10.1371/journal.pone.0163332
Linge J, Borga M, West J, Tuthill T, Miller MR, Dumitriu A, Thomas EL, et al. Body composition profiling in the UK biobank imaging study. Obesity. 2018;26:1785–95.
pubmed: 29785727
doi: 10.1002/oby.22210
Borga M, Ahlgren A, Romu T, Widholm P, Dahlqvist Leinhard O, West J. Reproducibility and repeatability of MRI-based body composition analysis. Magn Reson Med. 2020;84:3146–56.
pubmed: 32519807
doi: 10.1002/mrm.28360
Nasr P, Iredahl F, Dahlström N, Rådholm K, Henriksson P, Cedersund G, Dahlqvist Leinhard O, et al. Evaluating the prevalence and severity of NAFLD in primary care: the EPSONIP study protocol. BMC Gastroenterol. 2021;21:1.
doi: 10.1186/s12876-021-01763-z
Committee QMB. MR Elastography of the Liver, Quantitative Imaging Biomarkers Alliance. Profile Stage: Technically Confirmed. 2022 http://qibawiki.rsna.org/index.php/Profiles .
Blachier M, Leleu H, Peck-Radosavljevic M, Valla D-C, Roudot-Thoraval F. The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol. 2013;58:593–608.
pubmed: 23419824
doi: 10.1016/j.jhep.2012.12.005
Ekstedt M, Nasr P, Kechagias S. Natural history of NAFLD/NASH. Curr Hepatol Rep. 2017;16:391–7.
pubmed: 29984130
pmcid: 6022523
doi: 10.1007/s11901-017-0378-2
Taylor RS, Taylor RJ, Bayliss S, Hagström H, Nasr P, Schattenberg JM, Ishigami M, et al. Association between fibrosis stage and outcomes of patients with nonalcoholic fatty liver disease: a systematic review and Meta-analysis. Gastroenterology. 2020;158:1611–1625.e1612.
pubmed: 32027911
doi: 10.1053/j.gastro.2020.01.043
Ripoll C, Groszmann RJ, Garcia-Tsao G, Bosch J, Grace N, Burroughs A, Planas R, et al. Hepatic venous pressure gradient predicts development of hepatocellular carcinoma independently of severity of cirrhosis. J Hepatol. 2009;50:923–8.
pubmed: 19303163
pmcid: 3721146
doi: 10.1016/j.jhep.2009.01.014
Villanueva C, Torres F, Sarin SK, Shah HA, Tripathi D, Brujats A, Rodrigues SG, et al. Carvedilol reduces the risk of decompensation and mortality in patients with compensated cirrhosis in a competing-risk meta-analysis. J Hepatol. 2022;77:1014–25.
pubmed: 35661713
doi: 10.1016/j.jhep.2022.05.021
Kanwal F, Singal AG. Surveillance for hepatocellular carcinoma: current best practice and future direction. Gastroenterology. 2019;157:54–64.
pubmed: 30986389
doi: 10.1053/j.gastro.2019.02.049
Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, Lencioni R, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021;7:6.
pubmed: 33479224
doi: 10.1038/s41572-020-00240-3
Park HJ, Kim SY, Singal AG, Lee SJ, Won HJ, Byun JH, Choi SH, et al. Abbreviated magnetic resonance imaging vs ultrasound for surveillance of hepatocellular carcinoma in high-risk patients. Liver Int. 2022;42:2080–92.
pubmed: 34817921
doi: 10.1111/liv.15110
Huang DQ, Fowler KJ, Liau J, Cunha GM, Louie AL, An JY, Bettencourt R, et al. Comparative efficacy of an optimal exam between ultrasound versus abbreviated MRI for HCC screening in NAFLD cirrhosis: a prospective study. Aliment Pharmacol Ther. 2022;55:820–7.
pubmed: 35229334
pmcid: 9762322
doi: 10.1111/apt.16844
Marks RM, Ryan A, Heba ER, Tang A, Wolfson TJ, Gamst AC, Sirlin CB, et al. Diagnostic per-patient accuracy of an abbreviated hepatobiliary phase gadoxetic acid–enhanced MRI for hepatocellular carcinoma surveillance. Am J Roentgenol. 2015;204:527–35.
doi: 10.2214/AJR.14.12986
Besa C, Lewis S, Pandharipande PV, Chhatwal J, Kamath A, Cooper N, Knight-Greenfield A, et al. Hepatocellular carcinoma detection: diagnostic performance of a simulated abbreviated MRI protocol combining diffusion-weighted and T1-weighted imaging at the delayed phase post gadoxetic acid. Abdom Radiol. 2017;42:179–90.
doi: 10.1007/s00261-016-0841-5
Kang SH, Jeong WK, Baik SK, Cha SH, Kim MY. Impact of sarcopenia on prognostic value of cirrhosis: going beyond the hepatic venous pressure gradient and MELD score. J Cachexia Sarcopenia Muscle. 2018;9:860–70.
pubmed: 30371017
pmcid: 6204582
doi: 10.1002/jcsm.12333
Ha Y, Kim D, Han S, Chon YE, Lee YB, Kim MN, Lee JH, et al. Sarcopenia predicts prognosis in patients with newly diagnosed hepatocellular carcinoma, independent of tumor stage and liver function. Cancer Res Treat. 2018;50:843–51.
pubmed: 28882021
doi: 10.4143/crt.2017.232
Borga M, West J, Bell JD, Harvey NC, Romu T, Heymsfield SB, Dahlqvist LO. Advanced body composition assessment: from body mass index to body composition profiling. J Investig Med. 2018;66:1–9.
pubmed: 29581385
pmcid: 5992366
doi: 10.1136/jim-2018-000722