Diagnostic Performance of LIVERFASt as a Non-invasive Liver Fibrosis Test: Data from Three Cohorts of Patients with Metabolic Dysfunction-associated Steatotic Liver Disease

Naim Alkhouri; Parvez Mantry; Humberto C. Gonzalez; Rashmee Patil; Vicki McIntyre; Anita Kohli; Madhavi Rudraraju; Joseph Frank Kosinski; Bradley S. Vander Veen; Whitfield L. Knapple; Ravi Ravinuthala; Prasun Kumar Jalal; Sanjaya K. Satapathy; Bal Raj Bhandari; Christopher J. Christensen; Victor Ankoma-Sey; Quynh-An Phan; Fernando E. Membreno; Gabriel H. Lee; Sudha Kodali; Abdullah Mubarak; Hany A. Elbeshbeshy; Robert P. Morin Jr.; Reed B. Hogan II; Harry E. Sarles Jr; Brigitte Le Bail; Jean-Baptiste Hiriart; Juliette Foucher; Faiza Chermak; Marie Decraecker; Pamela Sylvestre; Matthew M. Yeh; Ronald Quiambao; Kimberly Mangee; James Tonascia; Medhi Sakka; Rana Alkouri; Maxime Deregnaucourt; Dominique Bonnefont-Rousselot; Stephen A. Harrison; Imtiaz Alam; Mona Munteanu; Meena Bansal; William Alazawi; Arun J. Sanyal

doi:10.15403/jgld-6432

Authors

Naim Alkhouri Department of Hepatology, Arizona Liver Health, Chandler, Arizona https://orcid.org/0000-0001-9872-2391
Parvez Mantry Methodist Health System, Dallas, Texas, https://orcid.org/0000-0003-4829-6931
Humberto C. Gonzalez Division of Gastroenterology and Hepatology, Henry Ford Health System, Detroit, Michigan; Wayne State University School of Medicine, Detroit, Michigan,
Rashmee Patil South Texas Research Institute, Edinburg, Texas, https://orcid.org/0000-0002-8345-0263
Vicki McIntyre Department of Hepatology, Arizona Liver Health, Tucson, Arizona
Anita Kohli Department of Hepatology, Arizona Liver Health, Peoria, Arizona
Madhavi Rudraraju Pinnacle Clinical Research, San Antonio (S.A.H., M.R.), Texas https://orcid.org/0009-0003-7618-466X
Joseph Frank Kosinski Premier Medical Group, Clarksville, Tennessee
Bradley S. Vander Veen Premier Medical Group, Clarksville, Tennessee,
Whitfield L. Knapple Arkansas Gastroenterology, North Little Rock, Arkansas, https://orcid.org/0009-0007-4081-3304
Ravi Ravinuthala Ohio Gastroenterology & Liver Institute (GCGA Physicians LLC), Cincinnati, Ohio https://orcid.org/0000-0002-9861-0784
Prasun Kumar Jalal Division of Gastroenterology, Baylor College of Medicine, Houston, Texas https://orcid.org/0000-0001-5353-2324
Sanjaya K. Satapathy 13. Department of Internal Medicine, Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases & Transplantation, Donald and Barbara Zucker School of Medicine for Hofstra/Northwell Health, Manhasset, New York, https://orcid.org/0000-0003-0153-2829
Bal Raj Bhandari 14. Delta Research Partners, Bastrop, Louisiana
Christopher J. Christensen Texas Digestive Disease Consultants PLLC d/b/a GI Alliance, Baton Rouge, Louisiana
Victor Ankoma-Sey Liver Associates of Texas, P.A., Houston, Texas
Quynh-An Phan Liver Associates of Texas, P.A., Houston, Texas https://orcid.org/0009-0002-8001-1473
Fernando E. Membreno DHR Health Institute for Research and Development, Edinburg, Texas
Gabriel H. Lee Texas Digestive Disease Consultants PLLC d/b/a GI Alliance, Webster, Texas
Sudha Kodali Sherrie and Alan Conover Center for Liver Disease and Transplantation, J. C. Walter Jr Transplant Center, Houston Methodist Hospital, Houston, Texas https://orcid.org/0000-0002-2816-9647
Abdullah Mubarak Liver Center of Texas, Dallas, Texas,
Hany A. Elbeshbeshy Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri https://orcid.org/0000-0002-6925-264X
Robert P. Morin Jr. Quality Research, Inc., San Antonio, Texas
Reed B. Hogan II Texas Digestive Disease Consultants PLLC d/b/a GI Alliance, Flowood, Mississippi https://orcid.org/0000-0002-8003-1485
Harry E. Sarles Jr Texas Digestive Disease Consultants PLLC d/b/a GI Alliance, Garland, Texas
Brigitte Le Bail Hepatology Unit, Hôpital Haut Lévêque, Bordeaux University Hospital, Bordeaux https://orcid.org/0000-0002-2607-1734
Jean-Baptiste Hiriart Pathology Department, University Hospital of Bordeaux, Bordeaux https://orcid.org/0000-0002-8863-8230
Juliette Foucher Hepatology Unit, Hôpital Haut Lévêque, Bordeaux University Hospital, Bordeaux https://orcid.org/0000-0003-2712-7469
Faiza Chermak Hepatology Unit, Hôpital Haut Lévêque, Bordeaux University Hospital, Bordeaux
Marie Decraecker Hepatology Unit, Hôpital Haut Lévêque, Bordeaux University Hospital, Bordeaux https://orcid.org/0000-0002-3304-2106
Pamela Sylvestre Department of Pathology Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio https://orcid.org/0009-0004-3278-7546
Matthew M. Yeh University of Washington School of Medicine, Department of Laboratory Medicine and Pathology, Seattle, Washington https://orcid.org/0000-0002-3004-8799
Ronald Quiambao Medical Affairs, Fibronostics, US Inc., Indian Harbour Beach, Florida https://orcid.org/0009-0003-2859-1447
Kimberly Mangee ObvioHealth, New York, New York
James Tonascia NIDDK Central Repositories. Bethesda, Maryland, USA. https://doi.org/10.58020/53bk-jk73
Medhi Sakka Metabolic Biochemistry Department, Pitié-Salpêtrière Hospital, Public Assistance Paris Hospitals, APHP Sorbonne University, Paris
Rana Alkouri Metabolic Biochemistry Department, Pitié-Salpêtrière Hospital, Public Assistance Paris Hospitals, APHP Sorbonne University, Paris
Maxime Deregnaucourt Metabolic Biochemistry Department, Pitié-Salpêtrière Hospital, Public Assistance Paris Hospitals, APHP Sorbonne University, Paris
Dominique Bonnefont-Rousselot 32. Metabolic Biochemistry Department, Pitié-Salpêtrière Hospital, Public Assistance Paris Hospitals, APHP Sorbonne University, Paris; 33. Pharmacy Training and Research Unit (UFR), Paris Cité University; CNRS, Inserm, UTCBS, Paris https://orcid.org/0000-0003-4689-9202
Stephen A. Harrison Pinnacle Clinical Research, San Antonio (S.A.H., M.R.), Texas
Imtiaz Alam Texas Tech University Health Science Center, Texas; 35. Tallahassee Memorial Hospital, Tallahassee, Florida
Mona Munteanu Medical Affairs, Fibronostics, US Inc., Indian Harbour Beach, Florida https://orcid.org/0000-0003-4517-2757
Meena Bansal Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York https://orcid.org/0000-0002-7501-2191
William Alazawi Barts Liver Centre, Blizard Institute, Queen Mary University of London, London https://orcid.org/0000-0002-3891-5914
Arun J. Sanyal Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia https://orcid.org/0000-0001-8682-5748

DOI:

https://doi.org/10.15403/jgld-6432

Keywords:

Metabolic Dysfunction-Associated Steatotic Liver Disease, Metabolic-Associated Steatohepatitis, MASLD, MASH, Liverfast, fibrosis, cirrhosis, steatohepatitis, non-invasive, biomarkers, resmetirom, FIB-4, NAFLD, advanced fibrosis, staging

Abstract

Aim: This study evaluates the diagnostic performance of the novel blood-based device, LIVERFASt to detect fibrosis stages in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), including those with type 2 diabetes (T2DM), compared to FIB-4 in a subgroup analysis.

Methods: LIVERFASt is computed with 10 blood biomarkers and four anthropometric measures and provides a quantitative score (0.00-1.00) to stage cirrhosis (F4), advanced fibrosis (≥F3), and clinically significant fibrosis (≥F2). Three cohorts of patients (two retrospective and one prospective) from tertiary centers in Europe and the U.S. with histological-proven biopsy were used to assess LIVERFASt and FIB-4 diagnostic performance using area under the receiver operating curve (AUROC), sensitivity (Sn), specificity, and predictive values (PV) for varying fibrosis prevalence levels.

Results: 497 MASLD adult patients were included (median age 56 years, 56.7% female, 50.3% T2DM, 44.1% advanced fibrosis, and 20.1% cirrhosis). In the pooled analysis, the AUROCs for fibrosis stages F4, ≥F3, and ≥F2 were: 0.868, 0.846, 0.748, as well as for the T2DM subgroup (n=250): 0.846, 0.798, 0.736, respectively. For 35% advanced fibrosis prevalence, the positive/negative PVs were 77.2%/81.3% for the overall cohort and 65.52%/79.81% for the subgroup with tT2DM, respectively. At high (90%) to low (1%) advanced fibrosis prevalences, the positive and negative PVs ranged from 93% to 4.28% and from 43.06% to 99.73%, respectively. For F4 and ≥F3 fibrosis stages, LIVERFASt outperformed FIB-4: AUROC 0.870 vs 0.851 and 0.874 vs 0.821 (p<0.01), with Sn 74.07 vs 48.15 and 65.54 vs 37.29, respectively.

Conclusions: LIVERFASt is a highly sensitive and clinically useful diagnostic test for staging fibrosis in MASLD patients, including those with T2DM and has a higher Sn for detecting advanced fibrosis when compared with FIB-4.