1. Accuracy of cytokeratin 18 (M30 and M65) in detecting non-alcoholic steatohepatitis and fibrosis: A systematic review and meta-analysis
- Author
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Quentin M. Anstee, Yasaman Vali, Patrick M.M. Bossuyt, Kevin L. Duffin, Jenny Lee, M. Julia Brosnan, Mohammad Hadi Zafarmand, Jérôme Boursier, Koos H. Zwinderman, Joanne Verheij, University of Denver, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), VU University Medical Center [Amsterdam], Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC - Academic medical center, Newcastle University [Newcastle], University of Amsterdam [Amsterdam] (UvA), Epidemiology and Data Science, Graduate School, Pathology, APH - Methodology, APH - Personalized Medicine, APH - Aging & Later Life, ARD - Amsterdam Reproduction and Development, and ACS - Atherosclerosis & ischemic syndromes
- Subjects
Liver Cirrhosis ,Male ,Epidemiology ,Physiology ,Biopsy ,[SDV]Life Sciences [q-bio] ,lcsh:Medicine ,Gastroenterology ,Biochemistry ,0302 clinical medicine ,Mathematical and Statistical Techniques ,Fibrosis ,Non-alcoholic Fatty Liver Disease ,Medicine and Health Sciences ,lcsh:Science ,ComputingMilieux_MISCELLANEOUS ,Multidisciplinary ,medicine.diagnostic_test ,Cell Death ,Liver Diseases ,Fatty liver ,Statistics ,Middle Aged ,Metaanalysis ,Research Assessment ,3. Good health ,Liver ,Physiological Parameters ,030220 oncology & carcinogenesis ,Meta-analysis ,Liver biopsy ,Physical Sciences ,Biomarker (medicine) ,Medicine ,030211 gastroenterology & hepatology ,Female ,Research Article ,Adult ,medicine.medical_specialty ,Systematic Reviews ,Science ,Surgical and Invasive Medical Procedures ,Gastroenterology and Hepatology ,Research and Analysis Methods ,03 medical and health sciences ,Cytokeratin ,Internal medicine ,medicine ,Humans ,Obesity ,Statistical Methods ,Keratin-18 ,business.industry ,Body Weight ,lcsh:R ,Biology and Life Sciences ,medicine.disease ,Peptide Fragments ,Morbid Obesity ,Fatty Liver ,Medical Risk Factors ,Hepatocytes ,lcsh:Q ,Steatohepatitis ,business ,Mathematics ,Biomarkers ,Developmental Biology - Abstract
IntroductionAssociation between elevated cytokeratin 18 (CK-18) levels and hepatocyte death has made circulating CK-18 a candidate biomarker to differentiate non-alcoholic fatty liver from non-alcoholic steatohepatitis (NASH). Yet studies produced variable diagnostic performance. We aimed to provide summary estimates with increased precision for the accuracy of CK-18 (M30, M65) in detecting NASH and fibrosis among non-alcoholic fatty liver disease (NAFLD) adults.MethodsWe searched five databases to retrieve studies evaluating CK-18 against a liver biopsy in NAFLD adults. Reference screening, data extraction and quality assessment (QUADAS-2) were independently conducted by two authors. Meta-analyses were performed for five groups based on the CK-18 antigens and target conditions, using one of two methods: linear mixed-effects multiple thresholds model or bivariate logit-normal random-effects model.ResultsWe included 41 studies, with data on 5,815 participants. A wide range of disease prevalence was observed. No study reported a pre-defined cut-off. Thirty of 41 studies provided sufficient data for inclusion in any of the meta-analyses. Summary AUC [95% CI] were: 0.75 [0.69-0.82] (M30) and 0.82 [0.69-0.91] (M65) for NASH; 0.73 [0.57-0.85] (M30) for fibrotic NASH; 0.68 (M30) for significant (F2-4) fibrosis; and 0.75 (M30) for advanced (F3-4) fibrosis. Thirteen studies used CK-18 as a component of a multimarker model.ConclusionsFor M30 we found lower diagnostic accuracy to detect NASH compared to previous meta-analyses, indicating a limited ability to act as a stand-alone test, with better performance for M65. Additional external validation studies are needed to obtain credible estimates of the diagnostic accuracy of multimarker models.
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- 2020
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