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August 2026

Letter: FDA Approval of the HepQuant SHUNT Liver Diagnostic Test and Clarification of the SHUNT-V Analysis Cohort

Mitchell Shiffman, K. Rajender Reddy, Michael D. Leise, Kamran Qureshi, Alastair D. Smith, Steve Helmke, John Kittelson, Michael P. McRae, Joanne C. Imperial, Gregory T. Everson | Alimentary Pharmacology and Therapeutics

A recent Letter to the Editor provides additional context regarding the difference between the SHUNT-V study population reported in Alimentary Pharmacology & Therapeutics and the clinical validation dataset included in the FDA-approved labeling for the HepQuant SHUNT® Liver Diagnostic Test. read more →

HepQuant SHUNT

May 2026

Evidence Supporting Utility of the Oral Cholate Challenge Test of Liver Function and Physiology to Aid Clinical Management: A Review of Analytical and Clinical Validation Studies

Andrew P. Keaveny, Kamran Qureshi, Mitchell Shiffman, Timothy R. Morgan, K. Rajender Reddy, Joanne C. Imperial, Michael P. McRae, Touraj Shokati, Gregory T. Everson | Gastro Hep Advances

Current liver assessments rely on liver stiffness measurements as surrogates for liver fibrosis or static laboratory values that reflect advanced disease or liver injury rather than overall hepatic function and physiology. The oral cholate challenge test (OCCT), HepQuant DuO® offers a noninvasive, blood-based, measure of liver function by assessing cholate clearance, which is hepatocyte specific and liver blood flow dependent. Clinical studies show its key metrics - Disease Severity Index (DSI), SHUNT%, and Hepatic Reserve - correlate with portal hypertension, varices, decompensation risk, and treatment response. These measures may outperform conventional liver tests and complement imaging or histology. The OCCT also shows promise as a monitoring tool in chronic liver disease drug trials, potentially improving both patient management and therapeutic development. read more →

HepQuant DuO

March 2026

Beyond LFTs, liver stiffness, and portal pressure: portal-systemic shunting as a new endpoint for clinical trials of cirrhosis and portal hypertension

Andrew P. Keaveny, Kamran Qureshi, Stuart C. Gordon, Joanne C. Imperial, Michael P. McRae, Touraj Shokati, Gregory T. Everson | Gastro Hep Advances

This commentary proposes the oral cholate challenge test (OCCT), specifically its Disease Severity Index (DSI) and measurement of portal-systemic shunting (SHUNT%), as a practical, clinically meaningful, and noninvasive complement or alternative to traditional tools like liver stiffness measurement and HVPG for assessing portal hypertension risk, esophageal varices, and prognosis in MASH-related cirrhosis. Since the OCCT directly reflects liver function and portal-systemic shunting, it could improve patient stratification and serve as a stronger endpoint for clinical management and drug development in this population. read more →

HepQuant DuO

July 2026

Simultaneous quantification of native human and transgenic porcine liver function in a decedent model of extracorporeal cross-circulation

Abraham Shaked, Michael P. McRae, Joanne C. Imperial, Leanne Lanieri, Alexander Sagar, Kim M. Olthoff, Susan Low, Kirsten G. Swenson, Peter Friend, Gregory T. Everson | American Journal of Transplantation

Porcine livers have the potential to support liver function via extracorporeal liver cross-circulation (ELC) until recovery or transplantation. To assess the functional integrity of both native human and porcine livers during ELC, we used the clearance of intravenously administered 13C-cholate to probe effective hepatic perfusion in 4 decedents maintained on ELC for 72 to 102 hours. Genetically modified porcine livers (EGEN-5784) were perfused using the OrganOx metra-ELC device. Hepatic filtration rate was calculated for the native human liver and the EGEN-5784 liver in ELC. During ELC, total hepatic filtration rate increased substantially compared with pre-ELC values, exceeded the upper limit of the normal range, and remained stable throughout the ELC period. Simultaneous measurement of cholate clearance in human and porcine livers during ELC provides real-time assessment of each organ’s functional contribution and may inform decisions regarding optimal ELC duration, timing of disconnection, and necessity of liver transplantation. read more →

February 2026

Extracorporeal liver cross-circulation using transgenic xenogeneic pig livers with brain-dead human decedents

Abraham Shaked, Alex Sagar, Kim M. Olthoff, Peter L. Abt, Emily A. Vail, Niels D. Martin, Charles S. Abrams, Rick D. Hasz, Christine Radolovic, Shannon Kaminski, Bao-Li Loza, James F. Markmann, Susan C. Low, Mike Curtis, Leanne Lanieri, Kirsten G. Swenson, Gregory T. Everson, David A. Wagner, Mohamed A. Elzawahry, John I. Fallon, Syed Hussain Abbas, Danielle Fortuna, Emma E. Furth, K. Rajender Reddy, Peter P. Reese & Peter Friend | Nature Medicine

Extracorporeal liver cross-circulation (ELC) using genetically modified pig livers may address an unmet need for temporary liver support in patients with acute or acute-on-chronic liver failure. read more →

February 2026

When should I repeat the endoscopy in my patient with compensated cirrhosis, whom I just scoped and who had no or small varices?

Imperial, Joanne C.; McRae, Michael P.; Everson, Gregory T. | Translational Gastroenterology and Hepatology

Current endoscopic surveillance intervals for patients with compensated advanced chronic liver disease (cACLD) are based primarily on the presence or size of esophageal varices and rely largely on expert opinion rather than objective risk stratification. In an analysis of 195 patients with no or small varices over an average follow-up of 5.3 years, the Disease Severity Index (DSI) from the HepQuant DuO test significantly predicted adverse clinical outcomes, demonstrating a stepwise increase in risk across stratified categories, while variceal size was not a significant predictor. These findings support incorporating DSI into surveillance strategies to better individualize the timing of repeat endoscopy and optimize care in cACLD. read more →

HepQuant DuO, HepQuant SHUNT

January 2026

HMG-CoA Reductase Inhibitors (Statins) May Preserve Hepatic Function and Reduce Portal-Systemic Shunting in Compensated Advanced Chronic Liver Disease: Results from the SHUNT-V Study

Rahimi, Robert S. MD, MSa; Mena, Edward MDb; Lucas, Kathryn J. MDc; McRae, Michael P. PhDd; Kittelson, John PhDe; Imperial, Joanne C. MDf; Smith, Alastair D. MB ChBg; Everson, Gregory T. MDf,*; for the SHUNT-V Subjects, Investigators, and Coordinators | Clinical and Translational Gastroenterology

Background and Aims: Factors associated with decline of hepatic function and increase in portal-systemic shunting, which herald clinical outcome in persons with compensated cirrhosis, are poorly characterized. We used cholate challenge to evaluate the associations of liver disease etiology, concomitant diabetes, and maintenance drug therapy, with the degree of hepatic dysfunction and portal-systemic shunting. Conclusions: Concomitant use of statins alone or in combination with metformin was independently associated with preserved hepatic function (DSI) and reduced portal-systemic shunting (SHUNT%). read more →

HepQuant DuO, HepQuant SHUNT

January 2026

Hepatic cholate clearance as assessed by HepQuant-SHUNT is predictive of clinical outcomes in individuals with Fontan circulation

Yuli Y. Kim, Daniel Ganger, Alexis Z. Tomlinson, Isabella Z. Farkas, Jack Rychik, Joanne Imperial, Michael P. McRae, Greg T. Everson, Maarouf A. Hoteit | International Journal of Cardiology Congenital Heart Disease

Fontan-associated liver disease [FALD] is universal in individuals with Fontan circulation [FC]. The dual cholate clearance test is a noninvasive, flow-dependent measure of liver function. We aim to explore the association between cholate clearance and clinical outcomes in this population. read more →

HepQuant SHUNT

January 2026

HepQuant DuO® Test Enhances Clinical Decision Making in Compensated Advanced Chronic Liver Disease

Kerry Whitaker, Joanne C. Imperial, Michael P. McRae, and Gregory T. Everson | Journal of Clinical Medicine | January 2026

The HepQuant DuO® test is a noninvasive, blood-based test that assesses global liver health by quantifying liver function and physiology. The test generates a disease severity index (DSI) for assessment of risk for portal hypertension and large esophageal varices (LEV) to aid in the upper endoscopy (EGD) decision, provides a definition of disease severity to aid in clinical management, and enables serial testing to monitor changes in liver health over time, either improvement or worsening. A DSI cutpoint 18.3 was defined in a U.S. multi-center trial in advanced chronic hepatitis C (HALT-C) and validated in a second U.S. multi-center trial where the majority of cases (52%) had MASLD/MASH (SHUNT-V). In addition, the latter validation study included all common etiologies of cACLD, and a high percentage of the study subjects were overweight, obese, elderly, and had diabetes. In several studies, DSI has shown favorable diagnostic performance compared to other noninvasive tests. Using real-world data, the analysis evaluated the impact of DSI 18.3 in the EGD decision and in modifying decision making in patients with cACLD. read more →

HepQuant DuO

October 2025

Initial Clinical Experience With the Oral Cholate ChallengeTest: Results From the 2023–2024 Early Access Program

Stuart C. Gordon | James Burton | Bhaktasharan Patel | for the EAP Participants | | Liver International Communications | October 2025

The oral cholate challenge test of liver health, intended for use in compensated advanced chronic liver disease, was launched through an Early Access Program (EAP) in 2023–2024. Tests were provided to 16 clinicians at five liver centres across the US. The tested patients (n = 129) represented a range of etiologies and stages of disease. Top clinical uses were: (1) informing the decision for endoscopy to test for varices (n = 56, 43%), (2) defining risk for large oesophageal varices (LEV) (n = 92, 71%), and (3)baseline for monitoring disease progression or treatment effects (n = 33, 26%). The test's disease severity index (DSI) stratified patients according to risk for portal hypertension and LEV: 49 (38%) low risk, 31 (24%) moderate risk and 49 (38%) high risk. The potential impact of DSI ≤ 18.3 on EGD avoidance (38%) in clinical practice replicated that which was observed in prior validation studies (41%). read more →

HepQuant DuO

November 2025

Cholate clearance: improving the assessment of liver health compared to current liver tests (LFTs)

James R. Burton, Jr., MD, Edward Mena, MD, Bhaktasharan Patel, MD | Gastro Hep Advances | November 2025

Current liver function tests (LFTs) either indicate late-stage disease or hepatobiliary injury but do not accurately measure liver function. True quantitative liver function tests, analogous to creatinine clearance for the kidneys, are needed for assessing liver health. read more →

HepQuant DuO

August 2025

The Cholate Challenge Test Quantified Baseline Functional Heterogeneity and Improvement in Response to Resmetirom in MASH-related Child Pugh A Cirrhosis

Naim Alkhouri, Michael P. McRae, Rebecca Taub, Brandon Hill, Joanne C. Imperial, John Kittelson, Sam E. Moussa, Gregory T. Everson | Gastro Hep Advances | August 2025

In this study of MASH-related Child-Pugh A cirrhosis (MASH cirrhosis), we used the cholate challenge test to quantify baseline disease severity and the subsequent impact of resmetirom treatment. read more →

HepQuant DuO

April 2025

Assessment of the performance of a dual-sample oral cholate challenge test: The HepQuant DuO test

Michael P. McRae, Touraj Shokati, Uwe Christians, Steve M. Helmke, Gregory T. Everson | Clinica Chimica Acta | April 2025

Liver health is currently evaluated using nonspecific blood tests, fibrosis surrogates, and invasive procedures, none of which directly measure liver function and physiology. The validated HepQuant SHUNT test quantifies liver function and physiology and is linked to clinical outcomes. Herein we present the reliability of a simplified version, the dual-sample oral cholate challenge (HepQuant DuO) test. read more →

HepQuant DuO

March 2025

Letter to the Editor: Enhancing the Diagnostic Performance of the Oral Cholate Challenge Test: Implications for Avoidance of Potentially Unnecessary Endoscopy

Tarek Hassanein, Andrew P. Keaveny, Parvez Mantry, Mitchell Shiffman, Michael Leise, Kamran Qureshi, Alastair D. Smith, Michael P. McRae, Joanne C. Imperial, Gregory T. Everson, the SHUNT-V Investigators | Alimentary Pharmacology & Therapeutics| March 2025

HepQuant DuO, HepQuant SHUNT

Alterations in Liver Perfusion in Adults with Fontan Circulation as Assessed by Dual Cholate Clearance

Yuli Y. Kim, Annique Nyman, Yuan-Shung Huang, Alexis Z. Tomlinson, Michael P. McRae, Greg T. Everson, Sumeet Vaikunth, Benjamin Rosenthal, Jack Rychik, Maarouf A. Hoteit | Journal of the American Heart Association | 2025 | March 2025

HepQuant SHUNT

March 2025

Rencofilstat Treatment Improves Liver Function in MASH With Advanced Fibrosis as Quantified by HepQuant DuO

Stephen A. Harrison, Patrick Mayo, Todd Hobbs, Caroline Zhao, Carlos Canizares, Robert Foster, Michael P. McRae, Steve M. Helmke, Gregory T. Everson | Liver International | 01 March 2025

HepQuant DuO, HepQuant SHUNT

November 2024

Measuring the Risk of Clinical Events (RISK ACE) by Quantifying Liver Function: A Patient-Centric Model

John Kittelson, Michael P. McRae, Gregory T. Everson | European Journal of Internal Medicine 2024; 132:160-163 | 29 November 2024

HepQuant DuO, HepQuant SHUNT

Cost-Effectiveness of an Oral Cholate Challenge Test for the Management of Patients at Risk for Large Esophageal Varices

Shailesh Chavan, Michael P. McRae, Kelly R. Pitts, Gregory T. Everson | Research Article | published 22 November 2024 PLOS ONE

HepQuant DuO, HepQuant SHUNT

Cholate Shunt, Oral Cholate Challenge and Endoscopic Lesions of Portal Hypertension: The SHUNT-V Study.

Mitchell Shiffman, K. Rajender Reddy, Michael, D. Leise3, Kamran Qureshi, Alastair D. Smith, Steve Helmke, John Kittelson, Michael P. McRae, Joanne C. Imperial, Gregory T. Everson, the SHUNT-V Investigators | Alimentary Pharmacology & Therapeutics, 2024; 61: 75-87

HepQuant DuO, HepQuant SHUNT

A Validated LC-MS/MS Assay for the Quantitation of Cholate Isotopes in Human Serum

Steve M. Helmke, Michael P. McRae, Uwe Christians, Touraj Shokati, Gregory T. Everson | The Journal of Applied Laboratory Medicine 2024 Aug 16

HepQuant DuO

The Oral Cholate Challenge Test Quantifies Risk for Liver-Related Clinical Outcomes in Primary Sclerosing Cholangitis

Steve Helmke, John Kittelson, Joanne Imperial, Michael McRae, Gregory T. Everson | Gastro Hep Advances 2024

HepQuant DuO

Editorial: Reading the cholate—A new gateway to portal hypertension and oesophageal varices: Authors’ reply

Tarek Hassanein, Andrew P. Keaveny, Parvez Mantry, Alastair D. Smith, Michael P. McRae, John Kittelson, Steve Helmke, Gregory T. Everson, for the SHUNT-V Investigators | Aliment Pharmacol Ther 2024

HepQuant DuO

Hepatic improvement within 27 days of avenciguat treatment in Child-Pugh A cirrhosis detected by an oral cholate challenge test

Eric J. Lawitz, Judith Ertle, Corinna Schoelch, Isabella Gashaw, Steve M. Helmke, Gregory T Everson | Liver Transplantation 2024 Jun 12

HepQuant SHUNT

Liver Function and Portal-Systemic Shunting Quantified by the Oral Cholate Challenge Test and Risk for Large Esophageal Varices

Tarek Hassanein, Andrew P. Keaveny, Parvez Mantry, Alastair D. Smith, Michael P. McRae, John Kittelson, Steve Helmke, Gregory T. Everson for the SHUNT-V Investigators | Aliment Pharmacol Ther 2024 May 22

HepQuant DuO

Hepatic Dysfunction Quantified by HepQuant DuO Outperforms Child-Pugh Classification in Predicting the Pharmacokinetics of Ampreloxetine

Jitendra Kanodia, Hugh Giovinazzo, Wayne Yates, David L. Bourdet, Steve M. Helmke, and Gregory T. Everson | Clin Pharmacol Ther 2024 Apr 23

HepQuant SHUNT

Within Individual Reproducibility of a Dual Sample Oral Cholate Challenge Test (DuO) and Simplified Versions of the HepQuant SHUNT Test

Michael P. McRae, John Kittelson, Steve M. Helmke, and Gregory T. Everson | Clin Translational Sci 2024

HepQuant DuO, HepQuant SHUNT

Dynamic elevation of aromatic amino acids in Hepatitis C Virus induced cirrhosis after a standard meal

Hill KL, Haddad JA, Ali RO, Zhang GY, Quinn GM, Townsend E, Everson GT, Helmke SM, Bagheri M, Schoenfeld M, Yang S, Koh C, Levy EB, Kleiner DE, Sacks DB, Etzion O, Heller T. | Clinical and Translational Gastroenterology 2024;15:e00666

HepQuant SHUNT

Advances in Noninvasive Measurement of Liver Function and Physiology: The HepQuant DuO Test

Michael P. McRae, John Kittelson, Steve M. Helmke, and Gregory T. Everson | Basic Clin Pharmacol Toxicol 2024 Jan 15. Mar;134(3):385-395

HepQuant DuO

Safety and pharmacokinetics of BI 685509, a soluble guanylyl cyclase activator, in patients with cirrhosis: A randomized Phase Ib study

Eric J. Lawitz, Thomas Reiberger, Jörn M. Schattenberg, Corinna Schoelch, Harvey O. Coxson, Diane Wong, Judith Ertle | Hepatology Communications. 2023 Mar 0;7:e0276

HepQuant SHUNT

Compartmental model describing the physiological basis for the HepQuant SHUNT test

Michael P. McRae, Steve M. Helmke, James R. Burton Jr., and Gregory T. Everson | Transl Res. Volume 252, P53-63, February 2023

HepQuant DuO, HepQuant SHUNT

HepQuant SHUNT Detects Portal Hypertension in Early Stages of Clinically Compensated Chronic Liver Disease

Wieland A, Etzion O, Ali RO, Levy E, Kleiner D, Helmke SM, Heller T, Everson GT | Clin Gastroenterol Hepatol. 2021 Apr 22;S1542-3565(21)00464-X

HepQuant SHUNT

Predicting clinical decompensation in patients with cirrhosis using the HepQuant SHUNT Test

Fallahzadeh MA, Hansen DJ, Trotter JF, Everson GT, Saracino G, Rahimi RS, Helmke S, Boutte J, Asrani SK | Aliment Pharmacol Ther. 2021 Apr;53(8):928-938

HepQuant SHUNT

Editorial: stratifying risk of adverse outcomes in cirrhosis: the Hepquant SHUNT test

Maan R, Sonneveld MJ | Aliment Pharmacol Ther. 2021 Apr;53(8):939-940

HepQuant SHUNT

Authors’ Response to “Editorial: stratifying risk of adverse outcomes in cirrhosis: the Hepquant SHUNT test”

Asrani S, Everson GT | Aliment Pharmacol Ther. 2021 Apr;53(8):941-942

HepQuant SHUNT

How clinicians may use tests of hepatic function now and in the future

Ghaziani TT, Kwo PY | Transl Res. 2021; 233:1-4

HepQuant SHUNT

Deterioration in liver function after liver-directed therapy for hepatocellular carcinoma measured by cholate clearance

Maarouf A. Hoteit, Andrezj Wojcieszynski, Brian Currie, Matthew H. Levine, Kimberly A. Forde, Kim A. Reiss, Greg Nadolski, Michael C. Soulen3, Steve Helmke, Gregory T. Everson, Edgar Ben-Josef | GastroHep. 2020;00:1–8

HepQuant SHUNT

Assessing hepatic impairment in Fontan‐associated liver disease using the HepQuant SHUNT test

Lemmer A, VanWagner L, Gasanova Z, Helmke S, Everson GT, Ganger D | Congenit Heart Dis. 2019; 14:978-986

HepQuant SHUNT

Noninvasive assessment of liver function

Helmke S, Colmenero J, Everson GT | Curr Opin Gastroenterol. 2015 May;31(3):199-208

HepQuant SHUNT

Functional Elements Associated With Hepatic Regeneration in Living Donors After Right Hepatic Lobectomy

Gregory T. Everson, John C. Hoefs, Claus U. Niemann, Kim M. Olthoff, Robert Dupuis, Shannon Lauriski, Andrea Herman, Norah Milne, Brenda W. Gillespie, Nathan P. Goodrich, and James E. Everhart | Liver Transpl 2013; 19:292–304

HepQuant SHUNT

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

Gregory T. Everson, Mitchell L. Shiffman, John C. Hoefs, Timothy R. Morgan, Richard K. Sterling, David A. Wagner, Shannon Lauriski, Teresa M. Curto, Anne Stoddard, and Elizabeth C. Wright, the HALT-C Trial Group | Hepatology 2012; 55:1019-1029

HepQuant SHUNT

Quantitative tests of liver function measure hepatic improvement after sustained virological response: Results from the HALT-C trial

Everson, G.T., Shiffman, M.L., Hoefs, J.C., Morgan, T.R., Sterling, R.K., Wagner, D.A., DeSanto, J.L., Curto, T., Wright, E.C., and the HALT-C Trial Group (2009) | Aliment Pharmacol Ther., 29(5):589-601

HepQuant SHUNT

The Spectrum of Hepatic Functional Impairment in Patients with Fibrosis and Compensated Cirrhosis Due to Chronic Hepatitis C: Results from the HALT-C Trial

Everson GT, Shiffman ML, Morgan TR, Hoefs JC, Sterling RK, Wagner DA, Kugelmas M, Curto T, Wright EC, and the HALT-C Trial Group (2008) | Aliment Pharmacol Ther. 27(9):798-809

HepQuant SHUNT

Portal-systemic shunting in patients with fibrosis or cirrhosis due to chronic hepatitis C: the minimal model for measuring cholate clearances and shunt

Everson GT, Martucci MA, Shiffman ML, Sterling RK, Morgan TR, Hoefs JC, The HALT-C Trial Group (2007) | Aliment Pharmacol Ther, 26(3):401-10

HepQuant SHUNT

Scientific Research: Posters & Presentations

Oral cholate challenge test stratifies hepatotoxicity risk after liver-directed therapy for hepatocellular carcinoma

Author: M. Hoteit, M.P. McRae, J.C. Imperial, G.T. Everson

Event: EASL Congress May 2026

Noninvasive Quantification of Liver Function and Portal-Systemic Shunting Distinguishes Differences between Child-Pugh A5 and A6 Cirrhosis

Author: N. Chalasani, M.L. Shiffman, T.R. Morgan, M.D. Leise, M.P. McRae, J.C. Imperial, G.T. Everson

Event: Baveno VIII Consensus Workshop

Noninvasive Quantification of Portal-Systemic Shunting: A New Approach to Assessment of the Portal Hypertension and the Portal Circulation

Author: J.C. Imperial, O. Etzion, T. Heller, E. Levy, D. Kleiner, R. Ali, M.P. McRae, G.T. Everson

Event: Baveno VIII Consensus Workshop