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. 2024 Jul;60(2):246-256.
doi: 10.1111/apt.18054. Epub 2024 May 22.

Liver function and portal-systemic shunting quantified by the oral cholate challenge test and risk for large oesophageal varices

Tarek Hassanein  1 , Andrew P Keaveny  2 , Parvez Mantry  3 , Alastair D Smith  4 , Michael P McRae  5 , John Kittelson  6 , Steve Helmke  7 , Gregory T Everson  7 ; SHUNT‐V Investigators
Collaborators, Affiliations

Liver function and portal-systemic shunting quantified by the oral cholate challenge test and risk for large oesophageal varices

Tarek Hassanein et al. Aliment Pharmacol Ther. 2024 Jul.

Abstract

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: 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: 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: 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: 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.

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Conflict of interest statement

Conflicts of Interest Disclosure: G.T. Everson (CEO) and S. Helmke (CSO) are equity members and employees of HepQuant LLC. They, in conjunction with the University of Colorado Denver Anschutz Medical Campus, have patents, both issued and pending, related to the dual cholate test (HepQuant SHUNT Test). G.T. Everson, S. Helmke, and M.P. McRae, in conjunction with HepQuant LLC, have provisional patents related to the oral cholate test (HepQuant DuO Test) and simplified versions of the SHUNT test. J. Kittelson and M.P. McRae are paid consultants for HepQuant LLC. All other authors have no conflicts of interest to declare.

Figures

Figure 1.
Figure 1.. Flowchart of study subjects in the HALT-C Trial Quantitative Liver Function Test (QLFT) ancillary study and the SHUNT-V Study.
Abbreviations: CP A, Child-Pugh A; EGD, esophagogastroduodenoscopy; LC-MS, liquid chromatography mass spectrometry.
Figure 2.
Figure 2.. Disease Severity Index (DSI) from DuO in controls (n=50) and subjects in the HALT-C and SHUNT-V studies (n=455) by subgroups according to body mass and variceal presence/size.
Abbreviations: Lean, controls of lean body mass; Overweight, controls with BMI ≥25; None, no oesophageal varices; Small, small oesophageal varices; Large, large oesophageal varices.
Figure 3.
Figure 3.. Diagnostic performance of Disease Severity Index (DSI) from DuO in predicting the presence of large oesophageal varices (LEVs) by esophagogastroduodenoscopy (EGD).
The plot of sensitivity and specificity versus DSI and corresponding 2×2 table for DSI ≤18.3 in ruling out LEVs is shown for HALT-C and SHUNT-V subjects (n=455).
Figure 4.
Figure 4.. Probability of finding large oesophageal varices (LEVs) in HALT-C and SHUNT-V (n=455) based on Disease Severity Index (DSI) from DuO (A) and calibration of predicted versus observed probabilities for quintiles of DSI (B).
Figure 5.
Figure 5.. Diagnostic performance of Disease Severity Index (DSI) from DuO with platelet count (PLT) in terms of large oesophageal varices (LEV) miss rate, endoscopy (EGD) avoidance, and any oesophageal varices (Any EV) miss rate.
Abbreviations: Any EV, any oesophageal varices (small and large); CP A, Child-Pugh class A cirrhosis; DSI, Disease Severity Index; EGD, esophagogastroduodenoscopy; LEV, large oesophageal varices; PLT, platelet count (103 μL−1).
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References

    1. 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. 2007/09/01 2007;46(3):922–938. doi: 10.1002/hep.21907 - DOI - PubMed
    1. 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. doi: 10.1016/j.jhep.2015.05.022 - DOI - PubMed
    1. Pateu E, Oberti F, Calès P. The noninvasive diagnosis of esophageal varices and its application in clinical practice. Clin Res Hepatol Gastroenterol. 2018/02/01/ 2018;42(1):6–16. doi: 10.1016/j.clinre.2017.07.006 - DOI - PubMed
    1. de Franchis R, Bosch J, Garcia-Tsao G, et al. Baveno VII - Renewing consensus in portal hypertension. J Hepatol. 2022;76(4):959–974. doi: 10.1016/j.jhep.2021.12.022 - DOI - PMC - PubMed
    1. 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. 2017/08/01 2017;37(8):1177–1183. doi: 10.1111/liv.13379 - DOI - PMC - PubMed

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