title: A population-based study on the prevalence of NASH using scores validated against liver histology.
abstract: OBJECTIVE
  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: Department of Medicine, University of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland. Electronic address: jenni.hyysalo@gmail.com.
authors: Jenni
authors: J
authors: Hyysalo
authors: Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Finland.
authors: Ville T
authors: VT
authors: Männistö
authors: Minerva Foundation Institute for Medical Research, Helsinki, Finland.
authors: You
authors: Y
authors: Zhou
authors: Department of Pathology, The Laboratory of Helsinki University Central Hospital, Finland.
authors: Johanna
authors: J
authors: Arola
authors: Department of Pathology, The Laboratory of Helsinki University Central Hospital, Finland.
authors: Vesa
authors: V
authors: Kärjä
authors: Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland.
authors: Marja
authors: M
authors: Leivonen
authors: Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland.
authors: Anne
authors: A
authors: Juuti
authors: Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland.
authors: Nabil
authors: N
authors: Jaser
authors: Department of Medicine, University of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland.
authors: Susanna
authors: S
authors: Lallukka
authors: Department of Surgery, University of Eastern Finland and Kuopio University Hospital, Finland.
authors: Pirjo
authors: P
authors: Käkelä
authors: Department of Surgery, University of Eastern Finland and Kuopio University Hospital, Finland.
authors: Sari
authors: S
authors: Venesmaa
authors: Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Finland.
authors: Marko
authors: M
authors: Simonen
authors: Department of Chronic Disease Prevention Unit, National Institute for Health and Welfare (THL), Helsinki, Finland; Department of Medicine, Central Finland Central Hospital, Jyväskylä, Finland.
authors: Juha
authors: J
authors: Saltevo
authors: Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Finland.
authors: Leena
authors: L
authors: Moilanen
authors: Department of Internal Medicine, Seinäjoki Central Hospital, Finland.
authors: Eeva
authors: E
authors: Korpi-Hyövalti
authors: Faculty of Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland; Unit of General Practice, Oulu University Hospital, Oulu, Finland.
authors: Sirkka
authors: S
authors: Keinänen-Kiukaanniemi
authors: Tampere University Hospital, Tampere, Finland.
authors: Heikki
authors: H
authors: Oksa
authors: Department of Clinical Sciences, Diabetes and Endocrinology, University Hospital Malmö, Lund University, Malmö, Sweden.
authors: Marju
authors: M
authors: Orho-Melander
authors: Department of Pathophysiology and Transplantation, Università degli Studi Milano, Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors: Luca
authors: L
authors: Valenti
authors: Department of Pathophysiology and Transplantation, Università degli Studi Milano, Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors: Silvia
authors: S
authors: Fargion
authors: Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Finland; Department of Medicine, Division of Internal Medicine, University of Helsinki, Helsinki, Finland.
authors: Jussi
authors: J
authors: Pihlajamäki
authors: Department of Chronic Disease Prevention Unit, National Institute for Health and Welfare (THL), Helsinki, Finland.
authors: Markku
authors: M
authors: Peltonen
authors: Department of Medicine, University of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland.
authors: Hannele
authors: H
authors: Yki-Järvinen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D007333:Insulin Resistance; D007558:Italy / Q000453:epidemiology; D008049:Lipase / Q000235:genetics; D008099:Liver / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D024821:Metabolic Syndrome / Q000150:complications; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology*; D009765:Obesity / Q000150:complications; D015995:Prevalence; D012307:Risk Factors; D055815:Young Adult; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
keywords: Alanine aminotransferase; Aspartate aminotransferase; Metabolic syndrome; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Type 2 diabetes