NASH - Disease Spotlight - Life Science Research

Translational Science for MASH Liver Disease Research

Liver disease associated protein profiling with The SomaScan® Assay and SomaSignal® Tests

Metabolic dysfunction Associated Steototic fatty Liver Disease, MASLD, previously known as NAFLD is characterized by the accumulation of fat in the liver and impacts as much as 1/3 of the US population. Thirty percent of patients with MASLD develop Metabolic Steatohepatitis, MASH, previously known as NASH. MASH can include fibrosis and signals the risk of the development of cirrhosis and liver cancer. Diagnosing the severity of MASLD and MASH has traditionally relied on invasive liver biopsies and histological examination.

A non-invasive, proteomics-based test for steatosis, ballooning, inflammation, and fibrosis is now available for research use only via the SomaSignal NASH tests.

The SomaSignal NASH tests use a binary scoring system to characterize samples as positive or negative for the four different indicators independent of diabetes status or presence/absence of therapeutic intervention. The SomaSignal NASH tests are available on their own or in conjunction with the full menu of 7,000 protein measurements derived from the SomaScan Assay.

MASH Analysis with Protein Profiling

SomaSignal Tests for MASH Analysis – Clinical indicators of disease progression

Liver disease diagram showing Steatosis, Inflammation, Fibrosis, and Ballooning

Protein profiling of blood with SomaSignal tests are the only technology capable of predicting all 4 MASH components simultaneously and non-invasively.

Measures steatosis, inflammation, fibrosis, and ballooning
Corresponds with staging as measured by liver biopsy
Reveals drug-mediated improvements in disease severity
Provides insight into treatment mechanism of action

Interested in high-plex protein profiling for biomarker and pathway discovery?

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MASH/NASH webinars

WebinarCorrelation of a nonalcoholic steatohepatitis proteomic test with clinical outcomes

In this webinar, Anne Minnich, PhD, biomarker consultant at Bristol Myers Squibb, presents research on the use of the new SomaSignal(TM) NASH bundle test in a recently completed clinical trial.

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WebinarA proteomics signature of NASH

There is a high unmet need for non-invasive tests that can robustly and reliably assess NAFLD for diagnosis, prognosis, and monitoring purposes. Large-scale profiling of serum/plasma proteins (proteomics) increasingly demonstrates utility to identify changes that accurately reflect and predict disease states and outcomes, including the fibrosis component of NASH that is driven by disease activity and remains the most robust histological marker of prognosis.

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WebinarDetect biomarkers associated with nonalcoholic fatty liver disease (NAFLD)

In this 1-hour discussion, learn how the SomaScan assay can be used to detect biomarkers associated with NAFLD—specifically, the identification of circulating proteins associated with fibrosis in NAFLD using a custom 5k-plex SomaScan assay. Also discussed is the importance of identifying non-invasive biomarkers that improve clinical decision-making and drug development for NAFLD, and the strategies for multiplexed validation of candidate biomarkers discovered using the SomaScan assay.

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WebinarGlobal NASH congress

Using the power of the world’s largest proteomic platform coupled with machine learning , clinical samples and known biopsy results were used to build proteomic models capable of staging steatosis , inflammation, ballooning and fibrosis, and diagnosing at-risk NASH. These models exhibit competitive performance vs. existing standard methods. Use-cases in drug development include a participant rule-out prior to biopsy and precision demonstration of pharmacodynamic mechanistic impacts on individual liver components with multiple longitudinal measurements. Combination of the liquid liver biopsy with other proteomic tests on the same platform can expand the assessment of drug impact to include changes in cardiovascular risk, insulin resistance, kidney function and body composition. This will result in smaller, faster and more comprehensive clinical trials in the future.

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Curated MASH research publications

Title	Author	Year	Journal	Volume	Issue	Pages	DOI	Accession number	Keywords	Abstract	All authors/Notes	Epub date
Effect of pegbelfermin on NASH and fibrosis-related biomarkers and correlation with histological response in the FALCON 1 trial	Elizabeth A. Brown, et al.	2023	JHEP Reports							FALCON 1 was a phase IIb study of pegbelfermin in patients with non-alcoholic steatohepatitis (NASH) and stage 3 fibrosis. This FALCON 1 post hoc analysis aimed to further assess the effect of pegbelfermin on NASH-related biomarkers, correlations between histological assessments and non-invasive biomarkers, and concordance between the week 24 histologically assessed primary endpoint response and biomarkers.	EA Brown, A Minnich, AJ Sanyal, R Loomba	01/04/2023
Machine learning algorithm improves detection of NASH (NAS-based) and at-risk NASH, a development and validation study	Lee J. et al.	2023	Hepatology
ADAMTSL2 protein and a soluble biomarker signature identify at-risk non-alcoholic steatohepatitis and fibrosis in adults with NAFLD	Corey KE, et al.	2022	J Hepatol	76	1	25-33	https://www.doi.org/10.1016/j.jhep.2021.09.026	34,600,973	ADAMTS Proteins/analysis Adult Area Under Curve Biomarkers/analysis Biopsy/methods/statistics & numerical data Case-Control Studies Cohort Studies Female Humans Liver Cirrhosis/blood/diagnosis/pathology Logistic Models Male Massachusetts Middle Aged Non-alcoholic Fatty Liver Disease/*diagnosis/pathology Prospective Studies ROC Curve Adamtsl2 biomarker fibrosis non-alcoholic fatty liver disease non-alcoholic steatohepatitis proteomics of Novartis. KEC serves on the scientific advisory board for Novo Nordisk and BMS and has received grant funding from Boehringer-Ingelheim, BMS and Novartis. All other authors have no conflicts of interest to declare. Please refer to the accompanying ICMJE disclosure forms for further details.	BACKGROUND & AIMS: Identifying fibrosis in non-alcoholic fatty liver disease (NAFLD) is essential to predict liver-related outcomes and guide treatment decisions. A protein-based signature of fibrosis could serve as a valuable, non-invasive diagnostic tool. This study sought to identify circulating proteins associated with fibrosis in NAFLD. METHODS: We used aptamer-based proteomics to measure 4,783 proteins in 2 cohorts (Cohort A and B). Targeted, quantitative assays coupling aptamer-based protein pull down and mass spectrometry (SPMS) validated the profiling results in a bariatric and NAFLD cohort (Cohort C and D, respectively). Generalized linear modeling-logistic regression assessed the ability of candidate proteins to classify fibrosis. RESULTS: From the multiplex profiling, 16 proteins differed significantly by fibrosis in cohorts A (n = 62) and B (n = 98). Quantitative and robust SPMS assays were developed for 8 proteins and validated in Cohorts C (n = 71) and D (n = 84). The A disintegrin and metalloproteinase with thrombospondin motifs like 2 (ADAMTSL2) protein accurately distinguished non-alcoholic fatty liver (NAFL)/non-alcoholic steatohepatitis (NASH) with fibrosis stage 0-1 (F0-1) from at-risk NASH with fibrosis stage 2-4, with AUROCs of 0.83 and 0.86 in Cohorts C and D, respectively, and from NASH with significant fibrosis (F2-3), with AUROCs of 0.80 and 0.83 in Cohorts C and D, respectively. An 8-protein panel distinguished NAFL/NASH F0-1 from at-risk NASH (AUROCs 0.90 and 0.87 in Cohort C and D, respectively) and NASH F2-3 (AUROCs 0.89 and 0.83 in Cohorts C and D, respectively). The 8-protein panel and ADAMTSL2 protein had superior performance to the NAFLD fibrosis score and fibrosis-4 score. CONCLUSION: The ADAMTSL2 protein and an 8-protein soluble biomarker panel are highly associated with at-risk NASH and significant fibrosis; they exhibited superior diagnostic performance compared to standard of care fibrosis scores. LAY SUMMARY: Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of liver disease worldwide. Diagnosing NAFLD and identifying fibrosis (scarring of the liver) currently requires a liver biopsy. Our study identified novel proteins found in the blood which may identify fibrosis without the need for a liver biopsy.	Corey, Kathleen E Pitts, Rebecca Lai, Michelle Loureiro, Joseph Masia, Ricard Osganian, Stephanie A Gustafson, Jenna L Hutter, Matthew M Gee, Denise W Meireles, Ozanan R Witkowski, Elan R Richards, Shola M Jacob, Jaison Finkel, Nancy Ngo, Debby Wang, Thomas J Gerszten, Robert E Ukomadu, Chinweike Jennings, Lori L eng P30 DK040561/DK/NIDDK NIH HHS/ R03 DK113349/DK/NIDDK NIH HHS/ R01 HL132320/HL/NHLBI NIH HHS/ R01 HL133870/HL/NHLBI NIH HHS/ R01 DK114144/DK/NIDDK NIH HHS/ Research Support, N.I.H., Extramural Netherlands J Hepatol. 2022 Jan;76(1):25-33. doi: 10.1016/j.jhep.2021.09.026. Epub 2021 Oct 1.I	04/10/2021
Liquid biomarkers for fibrotic NASH - progress in a complex field	Schuppan D, et al.	2022	J Hepatol	76	1	7-May	https://www.doi.org/10.1016/j.jhep.2021.11.005	34,801,249	Biomarkers Fibrosis Humans *Non-alcoholic Fatty Liver Disease/diagnosis Companion biomarker Nafld fibrogenesis liver biopsy liver fibrosis prediction serum marker arrangement or affiliation with any organization that may have a direct influence on their work. Please refer to the accompanying ICMJE disclosure forms for further details.		Schuppan, Detlef Myneni, Sudharani Surabattula, Rambabu eng Comment Editorial Research Support, Non-U.S. Gov't Netherlands J Hepatol. 2022 Jan;76(1):5-7. doi: 10.1016/j.jhep.2021.11.005. Epub 2021 Nov 17.I	01/01/1970
SOMAscan Proteomics Identifies Serum Biomarkers Associated With Liver Fibrosis in Patients With NASH	Luo Y, et al.	2021	Hepatol Commun	5	5	760-773	https://www.doi.org/10.1002/hep4.1670	34,027,267		Nonalcoholic steatohepatitis (NASH) is a major cause of liver-related morbidity and mortality worldwide. Liver fibrosis stage, a key component of NASH, has been linked to the risk of mortality and liver-related clinical outcomes. Currently there are no validated noninvasive diagnostics that can differentiate between fibrosis stages in patients with NASH; many existing tests do not reflect underlying disease pathophysiology. Noninvasive biomarkers are needed to identify patients at high-risk of NASH with advanced fibrosis. This was a retrospective study of patients with histologically proven NASH with fibrosis stages 0-4. The SOMAscan proteomics platform was used to quantify 1,305 serum proteins in a discovery cohort (n = 113). In patients with advanced (stages 3-4) versus early fibrosis (stages 0-2), 97 proteins with diverse biological functions were differentially expressed. Next, fibrosis-stage classification models were explored using a machine learning-based approach to prioritize the biomarkers for further evaluation. A four-protein model differentiated patients with stage 0-1 versus stage 2-4 fibrosis (area under the receiver operating characteristic curve [AUROC] = 0.74), while a 12-protein classifier differentiated advanced versus early fibrosis (AUROC = 0.83). Subsequently, the model's performance was validated in two independent cohorts (n = 71 and n = 32) with similar results (AUROC = 0.74-0.78). Our advanced fibrosis model performed similarly to or better than Fibrosis-4 index, aspartate aminotransferase-to-platelet ratio index, and nonalcoholic fatty liver disease (NAFLD) fibrosis score-based models for all three cohorts. Conclusion: A SOMAscan proteomics-based exploratory classifier for advanced fibrosis, consisting of biomarkers that reflect the complexity of NASH pathophysiology, demonstrated similar performance in independent validation cohorts and performed similarly or better than Fibrosis-4 index, aspartate aminotransferase-to-platelet ratio index, and NAFLD fibrosis score. Further studies are warranted to evaluate the clinical utility of these biomarker panels in patients with NAFLD.	Luo, Yi Wadhawan, Samir Greenfield, Alex Decato, Benjamin E Oseini, Abdul M Collen, Rebecca Shevell, Diane E Thompson, John Jarai, Gabor Charles, Edgar D Sanyal, Arun J eng Hepatol Commun. 2021 Jan 20;5(5):760-773. doi: 10.1002/hep4.1670. eCollection 2021 May.I	01/01/1970
Non-invasive assessment of non-alcoholic fatty liver disease: Clinical prediction rules and blood-based biomarkers	Vilar-Gomez E, et al.	2018	J Hepatol	68	2	305-315	https://www.doi.org/10.1016/j.jhep.2017.11.013	29,154,965	Biomarkers/blood Decision Support Techniques Humans Liver Cirrhosis/blood/diagnosis/etiology *Non-alcoholic Fatty Liver Disease/blood/complications/diagnosis Prognosis Apri Fib-4 Nafld Nash	The correct identification of patients at increased risk of non-alcoholic steatohepatitis (NASH) and advanced fibrosis is a critical step in the assessment of non-alcoholic fatty liver disease (NAFLD). Since liver biopsy is invasive, expensive and prone to sampling error, several clinical prediction rules and blood-based biomarkers have been developed as attractive and affordable alternatives for identification of patients at high risk of NASH and advanced fibrosis. Current biomarkers constitute predictive models (e.g. NAFLD fibrosis score, FIB-4 index and BARD score) or direct measures of inflammation (e.g. circulating keratin 18 fragments), or fibrosis (e.g. FibroTest(R), ELF or Pro-C3 tests). In the clinical setting, biomarkers may discriminate between patients with NASH or advanced fibrosis, predict dynamic changes in NASH/fibrosis over time, and provide long-term prognostic information. Although clinically useful, current biomarker predictions may be influenced by hepatic and extrahepatic conditions (e.g. age, patient comorbidities, and fibrosis or NASH prevalence), which may lead to inaccurate estimates in small subsamples of patients. No highly sensitive and specific tests are available to differentiate NASH from simple steatosis. However, diagnostic accuracy can be improved by combining blood biomarkers. NAFLD fibrosis score and FIB-4 index are both cost-effective and highly sensitive tools to exclude patients with advanced fibrosis. Moreover, their higher scores may identify patients at higher risk of non-liver- and liver-related morbidity and mortality. More expensive tests such as FibroTest or ELF are more specific for detection of patients with significant and advanced fibrosis. Recent efforts have concentrated on omics" approaches for developing and validating novel biomarkers. Herein, we describe currently available clinical prediction rules and blood-based biomarkers for identifying NASH and advanced fibrosis in patients with NAFLD, discussing their advantages and disadvantages, as well as their potential clinical utility for predicting dynamic changes over time and identifying patients at increased risk of adverse outcomes."	Vilar-Gomez, Eduardo Chalasani, Naga eng Review Netherlands J Hepatol. 2018 Feb;68(2):305-315. doi: 10.1016/j.jhep.2017.11.013. Epub 2017 Dec 2.I	01/01/1970

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The statements herein have not been evaluated by the Food and Drug Administration

Non-invasive proteomic analysis of liver health for MASH/NASH

Translational Science for MASH Liver Disease Research

Liver disease associated protein profiling with The SomaScan® Assay and SomaSignal® Tests

A non-invasive, proteomics-based test for steatosis, ballooning, inflammation, and fibrosis is now available for research use only via the SomaSignal NASH tests.

MASH Analysis with Protein Profiling

SomaSignal Tests for MASH Analysis – Clinical indicators of disease progression

Interested in high-plex protein profiling for biomarker and pathway discovery?

View the MASH tech note on our tech notes page to learn more.

MASH/NASH webinars

WebinarCorrelation of a nonalcoholic steatohepatitis proteomic test with clinical outcomes

WebinarA proteomics signature of NASH

WebinarDetect biomarkers associated with nonalcoholic fatty liver disease (NAFLD)

WebinarGlobal NASH congress

Curated MASH research publications

Additional resources

Additional SomaSignal tests

Contact one of our experts today