Biomarkers for staging fibrosis and non-alcoholic steatohepatitis in non-alcoholic fatty liver disease (the LITMUS project): a comparative diagnostic accuracy study

Autor: Yasaman Vali, Jenny Lee, Jerome Boursier, Salvatore Petta, Kristy Wonders, Dina Tiniakos, Pierre Bedossa, Andreas Geier, Sven Francque, Mike Allison, Georgios Papatheodoridis, Helena Cortez-Pinto, Raluca Pais, Jean-Francois Dufour, Diana Julie Leeming, Stephen A Harrison, Yu Chen, Jeremy F Cobbold, Michael Pavlides, Adriaan G Holleboom, Hannele Yki-Jarvinen, Javier Crespo, Morten Karsdal, Rachel Ostroff, Mohammad Hadi Zafarmand, Richard Torstenson, Kevin Duffin, Carla Yunis, Clifford Brass, Mattias Ekstedt, Guruprasad P Aithal, Jörn M Schattenberg, Elisabetta Bugianesi, Manuel Romero-Gomez, Vlad Ratziu, Quentin M Anstee, Patrick M Bossuyt
Přispěvatelé: Epidemiology and Data Science, APH - Methodology, APH - Personalized Medicine, Graduate School, Gastroenterology and Hepatology, Vascular Medicine, ACS - Diabetes & metabolism, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: lancet. Gastroenterology & hepatology. Elsevier Limited
Vali, Yasaman; Lee, Jenny; Boursier, Jerome; Petta, Salvatore; Wonders, Kristy; Tiniakos, Dina; Bedossa, Pierre; Geier, Andreas; Francque, Sven; Allison, Mike; Papatheodoridis, Georgios; Cortez-Pinto, Helena; Pais, Raluca; Dufour, Jean-Francois; Leeming, Diana Julie; Harrison, Stephen A; Chen, Yu; Cobbold, Jeremy F; Pavlides, Michael; Holleboom, Adriaan G; ... (2023). Biomarkers for staging fibrosis and non-alcoholic steatohepatitis in non-alcoholic fatty liver disease (the LITMUS project): a comparative diagnostic accuracy study. The lancet. Gastroenterology & hepatology, 8(8), pp. 714-725. Elsevier 10.1016/S2468-1253(23)00017-1
ISSN: 2468-1253
DOI: 10.1016/S2468-1253(23)00017-1
Popis: BACKGROUND The reference standard for detecting non-alcoholic steatohepatitis (NASH) and staging fibrosis-liver biopsy-is invasive and resource intensive. Non-invasive biomarkers are urgently needed, but few studies have compared these biomarkers in a single cohort. As part of the Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS) project, we aimed to evaluate the diagnostic accuracy of 17 biomarkers and multimarker scores in detecting NASH and clinically significant fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) and identify their optimal cutoffs as screening tests in clinical trial recruitment. METHODS This was a comparative diagnostic accuracy study in people with biopsy-confirmed NAFLD from 13 countries across Europe, recruited between Jan 6, 2010, and Dec 29, 2017, from the LITMUS metacohort of the prospective European NAFLD Registry. Adults (aged ≥18 years) with paired liver biopsy and serum samples were eligible; those with excessive alcohol consumption or evidence of other chronic liver diseases were excluded. The diagnostic accuracy of the biomarkers was expressed as the area under the receiver operating characteristic curve (AUC) with liver histology as the reference standard and compared with the Fibrosis-4 index for liver fibrosis (FIB-4) in the same subgroup. Target conditions were the presence of NASH with clinically significant fibrosis (ie, at-risk NASH; NAFLD Activity Score ≥4 and F≥2) or the presence of advanced fibrosis (F≥3), analysed in all participants with complete data. We identified thres holds for each biomarker for reducing the number of biopsy-based screen failures when recruiting people with both NASH and clinically significant fibrosis for future trials. FINDINGS Of 1430 participants with NAFLD in the LITMUS metacohort with serum samples, 966 (403 women and 563 men) were included after all exclusion criteria had been applied. 335 (35%) of 966 participants had biopsy-confirmed NASH and clinically significant fibrosis and 271 (28%) had advanced fibrosis. For people with NASH and clinically significant fibrosis, no single biomarker or multimarker score significantly reached the predefined AUC 0·80 acceptability threshold (AUCs ranging from 0·61 [95% CI 0·54-0·67] for FibroScan controlled attenuation parameter to 0·81 [0·75-0·86] for SomaSignal), with accuracy mostly similar to FIB-4. Regarding detection of advanced fibrosis, SomaSignal (AUC 0·90 [95% CI 0·86-0·94]), ADAPT (0·85 [0·81-0·89]), and FibroScan liver stiffness measurement (0·83 [0·80-0·86]) reached acceptable accuracy. With 11 of 17 markers, histological screen failure rates could be reduced to 33% in trials if only people who were marker positive had a biopsy for evaluating eligibility. The best screening performance for NASH and clinically significant fibrosis was observed for SomaSignal (number needed to test [NNT] to find one true positive was four [95% CI 4-5]), then ADAPT (six [5-7]), MACK-3 (seven [6-8]), and PRO-C3 (nine [7-11]). INTERPRETATION None of the single markers or multimarker scores achieved the predefined acceptable AUC for replacing biopsy in detecting people with both NASH and clinically significant fibrosis. However, several biomarkers could be applied in a prescreening strategy in clinical trial recruitment. The performance of promising markers will be further evaluated in the ongoing prospective LITMUS study cohort. FUNDING The Innovative Medicines Initiative 2 Joint Undertaking.
Databáze: OpenAIRE
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