2026-11-02 オックスフォード大学
＜関連情報＞
- https://www.ox.ac.uk/news/2026-11-03-breakthrough-in-non-invasive-liver-testing
- https://www.thelancet.com/journals/lanxxx/article/PIIS0140-6736(26)01145-1/abstract
- https://www.nature.com/articles/s41591-026-04496-2
代謝機能障害に伴う脂肪肝疾患における非侵襲的検査：LITMUS前向き多施設診断精度研究 Non-invasive tests in metabolic dysfunction-associated steatotic liver disease: the LITMUS prospective multicentre diagnostic accuracy study
Yasaman Vali, MD PhDa ∙ Kristy Wonders, MScb ∙ Jenny Lee, PhDa ∙ Prof Guruprasad P Aithal, MD PhD FRCPc ∙ Prof Rocio Aller, MDd,e ∙ Michael E D Allison, MD PhDf ∙ et al.
The Lancet Published: October 31, 2026
DOI:https://doi.org/10.1016/S0140-6736(26)01145-1
Summary
The advent of regulatory-approved pharmacological treatments for metabolic dysfunction-associated steatotic liver disease (MASLD) calls for precise, non-invasive biomarkers that facilitate early diagnosis, support therapy selection, and aid clinical trial enrolment. The European multicentre LITMUS study aimed to evaluate the diagnostic performance of a broad range of non-invasive biomarkers for identifying patients with metabolic dysfunction-associated steatohepatitis (MASH), at-risk MASH, advanced fibrosis, and cirrhosis.
In this prospective, multicentre, diagnostic accuracy study, adults with biopsy-confirmed MASLD were prospectively recruited across 13 countries in Europe and the USA. We assessed 12 single markers and 18 multimarker panels. The reference standard was centrally scored liver histology according to the non-alcoholic steatohepatitis Clinical Research Network Scoring System. Target conditions included MASH (Non-Alcoholic Fatty Liver Disease Activity Score ≥4 with ≥1 point per component), at-risk MASH (MASH plus significant fibrosis [fibrosis stage F≥2]), advanced fibrosis (F≥3), and cirrhosis (F4). Performance was evaluated by area-under-the-receiver operating characteristic curve (AUC), with the minimum acceptable criterion (MAC) of AUC higher than 0·80 to indicate potential biopsy replacement.
Between Jan 1, 2018, and June 30, 2023, we analysed data from 1590 participants with centrally scored liver biopsies and at least one biomarker measurement; 609 (38%) had biopsy-confirmed at-risk MASH, 678 (43%) had MASH, 585 (37%) had advanced fibrosis, and 164 (10%) had cirrhosis. For detecting at-risk MASH, SomaSignal showed the highest diagnostic performance (AUC 0·83 [95% CI 0·80–0·85]), significantly exceeding MAC, whereas no other test reached the MAC for MASH only. For advanced fibrosis, SomaSignal showed the highest performance (AUC 0·92 [0·90–0·94]), followed by FibroMeter-VCTE (AUC 0·87 [0·83–0·92]), Agile 3+ and TSP2 (both AUC 0·84 [0·82–0·86]), and NIS4 (0·82 [0·80–0·85]). For cirrhosis, FibroMeter-VCTE showed the highest diagnostic performance (AUC 0·94 [0·90–0·97]) followed by SomaSignal (AUC 0·92 [0·90–0·94]), followed by Agile 3+ (0·88 [0·85–0·91]), Agile 4 (0·87 [0·84–0·90]), ADAPT (0·85 [0·81–0·88]), and ELF, LSM-VCTE, and TSP2 (all 0·84 [0·81–0·87]). Sequential two-step approaches using gamma-glutamyl transferase as a first-line test met the MAC for both advanced fibrosis and at-risk MASH.
Although single markers resulted in variable and limited performance when compared to histology for detecting at-risk MASH, multimarker panels showed great potential, with a proteomic panel showing strong diagnostic performance. These findings could support the selection and implementation of non-invasive testing strategies in MASLD and inform future clinical guidelines, regulatory evaluation, and clinical trial design.
Innovative Medicines Initiative 2 Joint Undertaking.
MASLDにおける脂肪性肝炎および線維化の画像診断バイオマーカーと血清診断バイオマーカーの前向き検証：LITMUS画像研究 Prospective validation of imaging and serum diagnostic biomarkers of steatohepatitis and fibrosis in MASLD: the LITMUS Imaging Study
Michael Pavlides, Yasaman Vali, Ferenc E. Mózes, Kristy Wonders, Salma Akhtar, Paul D. Hockings, Elizabeth Shumbayawonda, Kay Pepin, Isabel Fernandez-Lizaranzu, Diana Julie Leeming, Jeremy F. Cobbold, Michael E. D. Allison, Guruprasad P. Aithal, Manuel Romero-Gomez, Rocio Aller, Juan M. Pericàs, Jérôme Boursier, Salvatore Petta, Jörn M. Schattenberg, Mattias Ekstedt, Annalisa Berzigotti, Hannele Yki-Järvinen, Miljen Martic, Theresa Tuthill, LITMUS Consortium Investigators, …Quentin M. Anstee
Nature Medicine Published:24 July 2026
DOI:https://doi.org/10.1038/s41591-026-04496-2
Abstract
There is a need for robust evaluations of noninvasive biomarkers for metabolic dysfunction-associated steatotic liver disease. This prospective multicenter study assessed the diagnostic accuracy of imaging (including liver stiffness measurement (LSM) using magnetic resonance elastography (MRE) and FibroScan (vibration-controlled transient elastography (VCTE)), serum biomarkers (including NIS2+) and composite scores (including Agile 3+ and Agile 4) for centrally read steatohepatitis and fibrosis. For cirrhosis, several biomarkers exceeded the minimum acceptable performance criterion (MAC), including MRE (area under the receiver operating curve (AUC) 0.91; P < 0.01), VCTE-LSM (AUC 0.87; P < 0.01), Agile 3+ (AUC 0.89; P < 0.01) and Agile 4 (AUC 0.88; P < 0.01). Among 357 participants, fibrosis stages F0–F4 were present in 12%, 16%, 25%, 32% and 15%, respectively. NIS2+ had the highest diagnostic accuracy among serum biomarkers for metabolic dysfunction-associated steatohepatitis (MASH; AUC 0.83) and at-risk MASH (MASH with at least stage 2 fibrosis; AUC 0.82), although neither significantly exceeded the MAC (P = 0.15 and P = 0.19). Among imaging biomarkers, MRE showed the highest performance for MASH (AUC 0.71) and at-risk MASH (AUC 0.75), but these remained below the MAC. For fibrosis staging, performance was stronger: MRE met the MAC for advanced fibrosis (AUC 0.91; P < 0.01), as did Agile 3+ (AUC 0.84; P = 0.03). For cirrhosis, several biomarkers exceeded the MAC, including MRE (AUC 0.91; P < 0.01), VCTE-LSM (AUC 0.87; P < 0.01), Agile 3+ (AUC 0.89; P < 0.01) and Agile 4 (AUC 0.88; P < 0.01). Serum biomarkers tended to outperform imaging for identifying at-risk MASH, whereas elastography and composite scores showed excellent accuracy for staging advanced fibrosis and cirrhosis.
