Diagnostic accuracy of non-invasive tests to screen for at-risk MASH-An individual participant data meta-analysis

Ferenc E Mózes¹, Jenny A Lee², Yasaman Vali², Emmanuel A Selvaraj^{1

3

4}, Arjun N A Jayaswal¹, Jérôme Boursier^{5

6}, Victor de Lédinghen^{7

8}, Monica Lupșor-Platon⁹, Yusuf Yilmaz^{10

11}, Wah-Kheong Chan¹², Sanjiv Mahadeva¹², Thomas Karlas¹³, Johannes Wiegand¹³, Shalimar¹⁴, Emmanouil Tsochatzis¹⁵, Antonio Liguori^{15

16}, Vincent Wai-Sun Wong¹⁷, Dae Ho Lee¹⁸, Adriaan G Holleboom¹⁹, Anne-Marieke van Dijk¹⁹, Anne Linde Mak¹⁹, Hannes Hagström^{20

21}, Camilla Akbari²¹, Masashi Hirooka²², Dong Hyeon Lee²³, Won Kim²³, Takeshi Okanoue²⁴, Toshihide Shima²⁴, Atsushi Nakajima²⁵, Masato Yoneda²⁵, Paul J Thuluvath^{26

27}, Feng Li²⁶, Annalisa Berzigotti^{28

29}, Yuly P Mendoza^{28

30}, Mazen Noureddin³¹, Emily Truong³², Céline Fournier-Poizat³³, Andreas Geier³⁴, Theresa Tuthill³⁵, Carla Yunis³⁶, Quentin M Anstee^{37

38}, Stephen A Harrison¹, Patrick M Bossuyt², Michael Pavlides^{1

3

4}

Affiliations

¹ Division of Cardiovascular Medicine, Radcliffe Department of Medicine, OCMR, University of Oxford, Oxford, UK.
² Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
³ Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
⁴ Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the University of Oxford, Oxford, UK.
⁵ Laboratoire HIFIH, UPRES EA 3859, SFR ICAT 4208, Université d'Angers, Angers, France.
⁶ Service d'Hépato-Gastroentérologie et Oncologie Digestive, Centre Hospitalier Universitaire d'Angers, Angers, France.
⁷ Centre d'Investigation de la Fibrose Hépatique, Hôpital Haut-Lévêque, Bordeaux University Hospital, Pessac, France.
⁸ INSERM1312, Bordeaux University, Bordeaux, France.
⁹ Department of Medical Imaging, Iuliu Hațieganu University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology "Prof.Dr. Octavian Fodor", Cluj-Napoca, Romania.
¹⁰ Department of Gastroenterology, School of Medicine, Marmara University, Istanbul, Turkey.
¹¹ Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey.
¹² Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
¹³ Department of Oncology, Gastroenterology, Hepatology, Pulmonology and Infectious Diseases, University Hospital Leipzig, Leipzig, Germany.
¹⁴ Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
¹⁵ Sheila Sherlock Liver Unit and UCL Institute for Liver and Digestive Health, Royal Free Hospital and University College London, London, UK.
¹⁶ Department of Translational Medicine and Surgery, Università Cattolica Del Sacro Cuore, Rome, Italy.
¹⁷ Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
¹⁸ Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea.
¹⁹ Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
²⁰ Division of Liver and Pancreatic diseases, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden.
²¹ Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
²² Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Touon, Ehime, Japan.
²³ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea.
²⁴ Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan.
²⁵ Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan.
²⁶ Institute of Digestive Health and Liver Diseases, Mercy Medical Center, Baltimore, Maryland, USA.
²⁷ Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
²⁸ Department for Visceral Medicine and Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
²⁹ Department of Biomedical Research, University of Bern, Bern, Switzerland.
³⁰ Graduate School for Health Sciences (GHS), University of Bern, Bern, Switzerland.
³¹ Houston Research Institute, Houston Methodist Hospital, Houston, Texas, USA.
³² Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
³³ Echosens, Paris, France.
³⁴ Division of Hepatology, University Hospital Würzburg, Würzburg, Germany.
³⁵ Internal Medicine Research Unit, Pfizer Inc, Cambridge, Massachusetts, USA.
³⁶ Clinical Development and Operations, Global Product Development, Pfizer, Inc, Lake Mary, Florida, USA.
³⁷ Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
³⁸ Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK.

PMID: 38573034
DOI: 10.1111/liv.15914

Free article

Meta-Analysis

Diagnostic accuracy of non-invasive tests to screen for at-risk MASH-An individual participant data meta-analysis

Ferenc E Mózes et al. Liver Int. 2024 Aug.

Free article

. 2024 Aug;44(8):1872-1885.

doi: 10.1111/liv.15914. Epub 2024 Apr 4.

Authors

Affiliations

¹ Division of Cardiovascular Medicine, Radcliffe Department of Medicine, OCMR, University of Oxford, Oxford, UK.
² Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
³ Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
⁴ Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the University of Oxford, Oxford, UK.
⁵ Laboratoire HIFIH, UPRES EA 3859, SFR ICAT 4208, Université d'Angers, Angers, France.
⁶ Service d'Hépato-Gastroentérologie et Oncologie Digestive, Centre Hospitalier Universitaire d'Angers, Angers, France.
⁷ Centre d'Investigation de la Fibrose Hépatique, Hôpital Haut-Lévêque, Bordeaux University Hospital, Pessac, France.
⁸ INSERM1312, Bordeaux University, Bordeaux, France.
⁹ Department of Medical Imaging, Iuliu Hațieganu University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology "Prof.Dr. Octavian Fodor", Cluj-Napoca, Romania.
¹⁰ Department of Gastroenterology, School of Medicine, Marmara University, Istanbul, Turkey.
¹¹ Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey.
¹² Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
¹³ Department of Oncology, Gastroenterology, Hepatology, Pulmonology and Infectious Diseases, University Hospital Leipzig, Leipzig, Germany.
¹⁴ Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
¹⁵ Sheila Sherlock Liver Unit and UCL Institute for Liver and Digestive Health, Royal Free Hospital and University College London, London, UK.
¹⁶ Department of Translational Medicine and Surgery, Università Cattolica Del Sacro Cuore, Rome, Italy.
¹⁷ Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
¹⁸ Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea.
¹⁹ Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
²⁰ Division of Liver and Pancreatic diseases, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden.
²¹ Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
²² Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Touon, Ehime, Japan.
²³ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea.
²⁴ Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan.
²⁵ Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan.
²⁶ Institute of Digestive Health and Liver Diseases, Mercy Medical Center, Baltimore, Maryland, USA.
²⁷ Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
²⁸ Department for Visceral Medicine and Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
²⁹ Department of Biomedical Research, University of Bern, Bern, Switzerland.
³⁰ Graduate School for Health Sciences (GHS), University of Bern, Bern, Switzerland.
³¹ Houston Research Institute, Houston Methodist Hospital, Houston, Texas, USA.
³² Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
³³ Echosens, Paris, France.
³⁴ Division of Hepatology, University Hospital Würzburg, Würzburg, Germany.
³⁵ Internal Medicine Research Unit, Pfizer Inc, Cambridge, Massachusetts, USA.
³⁶ Clinical Development and Operations, Global Product Development, Pfizer, Inc, Lake Mary, Florida, USA.
³⁷ Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
³⁸ Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK.

PMID: 38573034
DOI: 10.1111/liv.15914

Abstract

Background & aims: There is a need to reduce the screen failure rate (SFR) in metabolic dysfunction-associated steatohepatitis (MASH) clinical trials (MASH+F2-3; MASH+F4) and identify people with high-risk MASH (MASH+F2-4) in clinical practice. We aimed to evaluate non-invasive tests (NITs) screening approaches for these target conditions.

Methods: This was an individual participant data meta-analysis for the performance of NITs against liver biopsy for MASH+F2-4, MASH+F2-3 and MASH+F4. Index tests were the FibroScan-AST (FAST) score, liver stiffness measured using vibration-controlled transient elastography (LSM-VCTE), the fibrosis-4 score (FIB-4) and the NAFLD fibrosis score (NFS). Area under the receiver operating characteristics curve (AUROC) and thresholds including those that achieved 34% SFR were reported.

Results: We included 2281 unique cases. The prevalence of MASH+F2-4, MASH+F2-3 and MASH+F4 was 31%, 24% and 7%, respectively. Area under the receiver operating characteristics curves for MASH+F2-4 were .78, .75, .68 and .57 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F2-3 were .73, .67, .60, .58 for FAST, LSM-VCTE, FIB-4 and NFS. Area under the receiver operating characteristics curves for MASH+F4 were .79, .84, .81, .76 for FAST, LSM-VCTE, FIB-4 and NFS. The sequential combination of FIB-4 and LSM-VCTE for the detection of MASH+F2-3 with threshold of .7 and 3.48, and 5.9 and 20 kPa achieved SFR of 67% and sensitivity of 60%, detecting 15 true positive cases from a theoretical group of 100 participants at the prevalence of 24%.

Conclusions: Sequential combinations of NITs do not compromise diagnostic performance and may reduce resource utilisation through the need of fewer LSM-VCTE examinations.

Keywords: FAST; FIB‐4; LSM‐VCTE; MASH; NFS; at‐risk MASH; non‐invasive tests.

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References

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Diagnostic accuracy of non-invasive tests to screen for at-risk MASH-An individual participant data meta-analysis

Affiliations

Diagnostic accuracy of non-invasive tests to screen for at-risk MASH-An individual participant data meta-analysis

Authors

Affiliations

Abstract

References

REFERENCES

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous