Liver function and portal-systemic shunting quantified by the oral cholate challenge test and risk for large oesophageal varices.
Journal
Alimentary pharmacology & therapeutics
ISSN: 1365-2036
Titre abrégé: Aliment Pharmacol Ther
Pays: England
ID NLM: 8707234
Informations de publication
Date de publication:
22 May 2024
22 May 2024
Historique:
revised:
24
03
2024
received:
14
02
2024
accepted:
05
05
2024
medline:
23
5
2024
pubmed:
23
5
2024
entrez:
23
5
2024
Statut:
aheadofprint
Résumé
The quantitative HepQuant SHUNT test of liver function and physiology generates a disease severity index (DSI) that correlates with risk for clinical complications, such as large oesophageal varices (LEVs). A derivative test, HepQuant DuO, generates an equivalent DSI and simplifies testing by requiring only oral administration of the test solution and two blood samples at 20 and 60 min. Since the DSIs measured from DuO and SHUNT are equivalent, we compared the diagnostic performance for large oesophageal varices (LEVs) between the DSIs measured from DuO and SHUNT tests. This study combined the data from two prospectively conducted US studies: HALT-C and SHUNT-V. A total of 455 subjects underwent both the SHUNT test and esophagogastroduodenoscopy (EGD). DSI scores correlated with the probability of LEVs (p < 0.001) and demonstrated a stepwise increase from healthy lean controls without liver disease to subjects with chronic liver disease and no, small or large varices. Furthermore, a cutoff of DSI ≤ 18.3 from DuO had a sensitivity of 0.98 (missing only one case) and, if applied to the endoscopy (EGD) decision, would have prevented 188 EGDs (41.3%). The AUROC for DSI from DuO did not differ from that of the reference SHUNT test method (0.82 versus 0.81, p = 0.3500). DSI from HepQuant DuO links liver function and physiology to the risk of LEVs across a wide spectrum of patient characteristics, disease aetiologies and liver disease severity. DuO is minimally invasive, easy to administer, quantitative and may aid the decision to avoid or perform EGD for LEVs.
Sections du résumé
BACKGROUND
BACKGROUND
The quantitative HepQuant SHUNT test of liver function and physiology generates a disease severity index (DSI) that correlates with risk for clinical complications, such as large oesophageal varices (LEVs). A derivative test, HepQuant DuO, generates an equivalent DSI and simplifies testing by requiring only oral administration of the test solution and two blood samples at 20 and 60 min.
AIMS
OBJECTIVE
Since the DSIs measured from DuO and SHUNT are equivalent, we compared the diagnostic performance for large oesophageal varices (LEVs) between the DSIs measured from DuO and SHUNT tests.
METHODS
METHODS
This study combined the data from two prospectively conducted US studies: HALT-C and SHUNT-V. A total of 455 subjects underwent both the SHUNT test and esophagogastroduodenoscopy (EGD).
RESULTS
RESULTS
DSI scores correlated with the probability of LEVs (p < 0.001) and demonstrated a stepwise increase from healthy lean controls without liver disease to subjects with chronic liver disease and no, small or large varices. Furthermore, a cutoff of DSI ≤ 18.3 from DuO had a sensitivity of 0.98 (missing only one case) and, if applied to the endoscopy (EGD) decision, would have prevented 188 EGDs (41.3%). The AUROC for DSI from DuO did not differ from that of the reference SHUNT test method (0.82 versus 0.81, p = 0.3500).
CONCLUSIONS
CONCLUSIONS
DSI from HepQuant DuO links liver function and physiology to the risk of LEVs across a wide spectrum of patient characteristics, disease aetiologies and liver disease severity. DuO is minimally invasive, easy to administer, quantitative and may aid the decision to avoid or perform EGD for LEVs.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDDK NIH HHS
ID : M01RR-00051
Pays : United States
Organisme : NIDDK NIH HHS
ID : M01RR-00827
Pays : United States
Organisme : NIDDK NIH HHS
ID : M01RR-00065
Pays : United States
Organisme : National Institute of Allergy and Infectious Diseases
Organisme : NCI NIH HHS
Pays : United States
Organisme : National Center on Minority Health and Health Disparities
Organisme : NIH General Clinical Research Centers
Organisme : Hoffmann-La Roche, Inc.
Investigateurs
Kiran Bambha
(K)
Michael Fuchs
(M)
Richard K Gilroy
(RK)
K Rajender Reddy
(KR)
Mitchell L Shiffman
(ML)
Robert S Rahimi
(RS)
Paul A Hellstern
(PA)
John M Hill
(JM)
Zeid Kayali
(Z)
Doug Denham
(D)
Kamran Qureshi
(K)
Brian Smith
(B)
K Jean Lucas
(KJ)
Michael D Leise
(MD)
Sarah Glover
(S)
Thomas D Amankonah
(TD)
Buck Patel
(B)
Gary Reiss
(G)
Fredric B Newman
(FB)
Vishal K Bhagat
(VK)
Wing-Kin Syn
(WK)
Edward Mena
(E)
Anita Kohli
(A)
Natarajan Ravendhran
(N)
James Strobel
(J)
Informations de copyright
© 2024 John Wiley & Sons Ltd.
Références
Garcia‐Tsao G, Sanyal AJ, Grace ND, Carey W. Practice Guidelines Committee of the American Association for the Study of Liver Diseases, the Practice Parameters Committee of the American College of Gastroenterology. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007;46(3):922–938. https://doi.org/10.1002/hep.21907
de Franchis R. Expanding consensus in portal hypertension: report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015;63(3):743–752. https://doi.org/10.1016/j.jhep.2015.05.022
Pateu E, Oberti F, Calès P. The noninvasive diagnosis of esophageal varices and its application in clinical practice. Clin Res Hepatol Gastroenterol. 2018;42(1):6–16. https://doi.org/10.1016/j.clinre.2017.07.006
de Franchis R, Bosch J, Garcia‐Tsao G, Reiberger T, Ripoll C, Abraldes JG, et al. Baveno VII ‐ renewing consensus in portal hypertension. J Hepatol. 2022;76(4):959–974. https://doi.org/10.1016/j.jhep.2021.12.022
Jangouk P, Turco L, De Oliveira A, Schepis F, Villa E, Garcia‐Tsao G. Validating, deconstructing and refining Baveno criteria for ruling out high‐risk varices in patients with compensated cirrhosis. Liver Int. 2017;37(8):1177–1183. https://doi.org/10.1111/liv.13379
Helmke S, Colmenero J, Everson GT. Noninvasive assessment of liver function. Curr Opin Gastroenterol. 2015;31(3):199–208.
Everson GT, Martucci MA, Shiffman ML, Sterling RK, Morgan TR, Hoefs JC, et al. Portal‐systemic shunting in patients with fibrosis or cirrhosis due to chronic hepatitis C: the minimal model for measuring cholate clearances and shunt. Aliment Pharmacol Ther. 2007;26(3):401–410. https://doi.org/10.1111/j.1365‐2036.2007.03389.x
Everson GT, Shiffman ML, Morgan TR, Hoefs JC, Sterling RK, Wagner DA, et al. The spectrum of hepatic functional impairment in compensated chronic hepatitis C: results from the Hepatitis C anti‐viral long‐term treatment against cirrhosis trial. Aliment Pharmacol Ther. 2008;27(9):798–809. https://doi.org/10.1111/j.1365‐2036.2008.03639.x
Everson GT, Shiffman ML, Hoefs JC, Morgan TR, Sterling RK, Wagner DA, et al. Quantitative liver function tests improve the prediction of clinical outcomes in chronic hepatitis C: results from the hepatitis C antiviral long‐term treatment against cirrhosis trial. Hepatology. 2012;55(4):1019–1029. https://doi.org/10.1002/hep.24752
Fallahzadeh MA, Hansen DJ, Trotter JF, Everson GT, Saracino G, Rahimi RS, et al. Predicting clinical decompensation in patients with cirrhosis using the Hepquant‐SHUNT test. Aliment Pharmacol Ther. 2021;53(8):928–938. https://doi.org/10.1111/apt.16283
Shrestha R, McKinley C, Showalter R, Wilner K, Marsano L, Vivian B, et al. Quantitative liver function tests define the functional severity of liver disease in early‐stage cirrhosis. Liver Transpl Surg. 1997;3(2):166–173. https://doi.org/10.1002/lt.500030210
McRae MP, Kittelson J, Helmke SM, Everson GT. Advances in noninvasive measurement of liver function and physiology: the HepQuant DuO test. Basic Clin Pharmacol Toxicol. 2024;134(3):385–395. https://doi.org/10.1111/bcpt.13980
European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; Clinical Practice Guideline Panel; Chair:; EASL Governing Board representative:; Panel members. EASL‐ALEH clinical practice guidelines: non‐invasive tests for evaluation of liver disease severity and prognosis. J Hepatol. 2015;63(1):237–264. https://doi.org/10.1016/j.jhep.2015.04.006
Berzigotti A, Tsochatzis E, Boursier J, Castera L, Cazzagon N, Friedrich‐Rust M, et al. EASL Clinical Practice Guidelines on non‐invasive tests for evaluation of liver disease severity and prognosis; 2021 update. J Hepatol. 2021;75(3):659–689. https://doi.org/10.1016/j.jhep.2021.05.025
Everson GT, Shiffman ML, Hoefs JC, Morgan TR, Sterling RK, Wagner DA, et al. Quantitative tests of liver function measure hepatic improvement after sustained virological response: results from the HALT‐C trial. Aliment Pharmacol Ther. 2009;29(5):589–601. https://doi.org/10.1111/j.1365‐2036.2008.03908.x
Lee WM, Dienstag JL, Lindsay KL, Lok AS, Bonkovsky HL, Shiffman ML, et al. Evolution of the HALT‐C Trial: pegylated interferon as maintenance therapy for chronic hepatitis C in previous interferon nonresponders. Control Clin Trials. 2004;25(5):472–492. https://doi.org/10.1016/j.cct.2004.08.003
Burton JR, Helmke S, Lauriski S, Kittelson J, Everson GT. The within‐individual reproducibility of the disease severity index from the HepQuant SHUNT test of liver function and physiology. Transl Res. 2021;233:5–15. https://doi.org/10.1016/j.trsl.2020.12.010
McRae MP, Kittelson J, Helmke SM, Everson GT. Within individual reproducibility of a dual sample Oral cholate challenge test (DuO) and other simplified versions of the HepQuant test. Clin Transl Sci. 2024;17(4):e13786. https://doi.org/10.1111/cts.13786
Lemmens HJ, Bernstein DP, Brodsky JB. Estimating blood volume in obese and morbidly obese patients. Obes Surg. 2006;16(6):773–776. https://doi.org/10.1381/096089206777346673
McRae MP, Helmke SM, Burton JR Jr, Everson GT. Compartmental model describing the physiological basis for the HepQuant SHUNT test. Transl Res. 2023;252:53–63. https://doi.org/10.1016/j.trsl.2022.08.002
McRae MP, Helmke SM, Everson GT. Liver function measured by HepQuant DuO predicts the likelihood for large esophageal varices in Child‐Pugh A cirrhosis (late‐breaking abstract 5026‐C). 2024 Presented at: The Liver Meeting; 2024, Boston, Massachusetts.
DeLong ER, DeLong DM, Clarke‐Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44(3):837–845.
Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez JC, et al. pROC: an open‐source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics. 2011;12(1):77. https://doi.org/10.1186/1471‐2105‐12‐77
Hosmer DW, Lemeshow S. Applied logistic regression. 2nd ed. Hoboken, NJ: John Wiley & Sons, Inc.; 2004.
McRae MP, Helmke SM, Everson GT. Next generation HepQuant tests predict clinical outcome in primary sclerosing cholangitis (abstract 4559‐C). 2023 Presented at: the liver meeting; Boston, Massachusetts.
Angeli P, Bernardi M, Villanueva C, Francoz C, Mookerjee RP, Trebicka J, et al. EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69(2):406–460. https://doi.org/10.1016/j.jhep.2018.03.024
Wong VW‐S, Irles M, Wong GL‐H, Shili S, Chan AWH, Merrouche W, et al. Unified interpretation of liver stiffness measurement by M and XL probes in non‐alcoholic fatty liver disease. Gut. 2019;68(11):2057–2064. https://doi.org/10.1136/gutjnl‐2018‐317334
Abraldes JG, Bureau C, Stefanescu H, Augustin S, Ney M, Blasco H, et al. Noninvasive tools and risk of clinically significant portal hypertension and varices in compensated cirrhosis: the “Anticipate” study. Hepatology. 2016;64(6):2173–2184. https://doi.org/10.1002/hep.28824
Pons M, Augustin S, Scheiner B, Guillaume M, Rosselli M, Rodrigues SG, et al. Noninvasive diagnosis of portal hypertension in patients with compensated advanced chronic liver disease. Am J Gastroenterol. 2021;116(4):723–732.
Wieland A, Etzion O, Ali R, Levy E, Kleiner DE, Helmke SM, et al. HepQuant SHUNT detects portal hypertension in early stages of clinically compensated chronic liver disease. Clin Gastroenterol Hepatol. 2021;20:e890–e894. https://doi.org/10.1016/j.cgh.2021.04.030