Jenni Hyysalo1, Ville T Männistö2, You Zhou3, Johanna Arola4, Vesa Kärjä4, Marja Leivonen5, Anne Juuti5, Nabil Jaser5, Susanna Lallukka6, Pirjo Käkelä7, Sari Venesmaa7, Marko Simonen2, Juha Saltevo8, Leena Moilanen2, Eeva Korpi-Hyövalti9, Sirkka Keinänen-Kiukaanniemi10, Heikki Oksa11, Marju Orho-Melander12, Luca Valenti13, Silvia Fargion13, Jussi Pihlajamäki14, Markku Peltonen15, Hannele Yki-Järvinen6. 1. Department of Medicine, University of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland. Electronic address: jenni.hyysalo@gmail.com. 2. Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Finland. 3. Minerva Foundation Institute for Medical Research, Helsinki, Finland. 4. Department of Pathology, The Laboratory of Helsinki University Central Hospital, Finland. 5. Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland. 6. Department of Medicine, University of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland. 7. Department of Surgery, University of Eastern Finland and Kuopio University Hospital, Finland. 8. Department of Chronic Disease Prevention Unit, National Institute for Health and Welfare (THL), Helsinki, Finland; Department of Medicine, Central Finland Central Hospital, Jyväskylä, Finland. 9. Department of Internal Medicine, Seinäjoki Central Hospital, Finland. 10. Faculty of Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland; Unit of General Practice, Oulu University Hospital, Oulu, Finland. 11. Tampere University Hospital, Tampere, Finland. 12. Department of Clinical Sciences, Diabetes and Endocrinology, University Hospital Malmö, Lund University, Malmö, Sweden. 13. Department of Pathophysiology and Transplantation, Università degli Studi Milano, Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 14. Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Finland; Department of Medicine, Division of Internal Medicine, University of Helsinki, Helsinki, Finland. 15. Department of Chronic Disease Prevention Unit, National Institute for Health and Welfare (THL), Helsinki, Finland.
Abstract
BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease in Western countries. Diagnosis of NASH requires a liver biopsy. We estimated the prevalence of NASH non-invasively in a population-based study using scores validated against liver histology. METHODS: Clinical characteristics, PNPLA3 genotype at rs738409, and serum cytokeratin 18 fragments were measured in 296 consecutive bariatric surgery patients who underwent a liver biopsy to discover and validate a NASH score ('NASH score'). We also defined the cut-off for NASH for a previously validated NAFLD liver fat score to diagnose NASH in the same cohort ('NASH liver fat score'). Both scores were validated in an Italian cohort comprising of 380, mainly non-bariatric surgery patients, who had undergone a liver biopsy for NASH. The cut-offs were utilized in the Finnish population-based D2D-study involving 2849 subjects (age 45-74 years) to estimate the population prevalence of NASH. RESULTS: The final 'NASH Score' model included PNPLA3 genotype, AST and fasting insulin. It predicted NASH with an AUROC 0.774 (0.709, 0.839) in Finns and 0.759 (0.711, 0.807) in Italians (NS). The AUROCs for 'NASH liver fat score' were 0.734 (0.664, 0.805) and 0.737 (0.687, 0.787), respectively. Using 'NASH liver fat score' and 'NASH Score', the prevalences of NASH in the D2D study were 4.2% (95% CI: 3.4, 5.0) and 6.0% (5.0, 6.9%). Sensitivity analysis was performed by taking into account stochastic false-positivity and false-negativity rates in a Bayesian model. This analysis yielded population prevalences of NASH of 3.1% (95% stimulation limits 0.2-6.8%) using 'NASH liver fat score' and 3.6% (0.2-7.7%) using 'NASH Score'. CONCLUSIONS: The population prevalence of NASH in 45-74 year old Finnish subjects is ∼ 5%.
BACKGROUND & AIMS:Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease in Western countries. Diagnosis of NASH requires a liver biopsy. We estimated the prevalence of NASH non-invasively in a population-based study using scores validated against liver histology. METHODS: Clinical characteristics, PNPLA3 genotype at rs738409, and serum cytokeratin 18 fragments were measured in 296 consecutive bariatric surgery patients who underwent a liver biopsy to discover and validate a NASH score ('NASH score'). We also defined the cut-off for NASH for a previously validated NAFLD liver fat score to diagnose NASH in the same cohort ('NASH liver fat score'). Both scores were validated in an Italian cohort comprising of 380, mainly non-bariatric surgery patients, who had undergone a liver biopsy for NASH. The cut-offs were utilized in the Finnish population-based D2D-study involving 2849 subjects (age 45-74 years) to estimate the population prevalence of NASH. RESULTS: The final 'NASH Score' model included PNPLA3 genotype, AST and fasting insulin. It predicted NASH with an AUROC 0.774 (0.709, 0.839) in Finns and 0.759 (0.711, 0.807) in Italians (NS). The AUROCs for 'NASH liver fat score' were 0.734 (0.664, 0.805) and 0.737 (0.687, 0.787), respectively. Using 'NASH liver fat score' and 'NASH Score', the prevalences of NASH in the D2D study were 4.2% (95% CI: 3.4, 5.0) and 6.0% (5.0, 6.9%). Sensitivity analysis was performed by taking into account stochastic false-positivity and false-negativity rates in a Bayesian model. This analysis yielded population prevalences of NASH of 3.1% (95% stimulation limits 0.2-6.8%) using 'NASH liver fat score' and 3.6% (0.2-7.7%) using 'NASH Score'. CONCLUSIONS: The population prevalence of NASH in 45-74 year old Finnish subjects is ∼ 5%.
Authors: Cyrielle Caussy; Veeral H Ajmera; Puneet Puri; Cynthia Li-Shin Hsu; Shirin Bassirian; Mania Mgdsyan; Seema Singh; Claire Faulkner; Mark A Valasek; Emily Rizo; Lisa Richards; David A Brenner; Claude B Sirlin; Arun J Sanyal; Rohit Loomba Journal: Gut Date: 2018-12-19 Impact factor: 23.059
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Authors: Zhenghui G Jiang; Elliot B Tapper; Margery A Connelly; Carolina F M G Pimentel; Linda Feldbrügge; Misung Kim; Sarah Krawczyk; Nezam Afdhal; Simon C Robson; Mark A Herman; James D Otvos; Kenneth J Mukamal; Michelle Lai Journal: Liver Int Date: 2016-02-24 Impact factor: 5.828