A population-based study on the prevalence of NASH using scores validated against liver histology

Jenni Hyysalo, Ville T. Männistö, You Zhou, Johanna Arola, Vesa Kärjä, Marja Leivonen, Anne Juuti, Nabil Jaser, Susanna Lallukka, Pirjo Käkelä, Sari Venesmaa, Marko Simonen, Juha Saltevo, Leena Moilanen, Eeva Korpi-Hyövalti, Sirkka Keinänen-Kiukaanniemi, Heikki Oksa, Marju Orho-Melander, Luca Valenti, Silvia FargionJussi Pihlajamäki, Markku Peltonen, Hannele Yki-Järvinen

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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%.

Original languageEnglish
Pages (from-to)839-846
Number of pages8
JournalJournal of Hepatology
Volume60
Issue number4
DOIs
Publication statusPublished - 2014

Keywords

  • Alanine aminotransferase
  • Aspartate aminotransferase
  • Metabolic syndrome
  • Non-alcoholic fatty liver disease
  • Non-alcoholic steatohepatitis
  • Type 2 diabetes

ASJC Scopus subject areas

  • Hepatology
  • Medicine(all)

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    Hyysalo, J., Männistö, V. T., Zhou, Y., Arola, J., Kärjä, V., Leivonen, M., Juuti, A., Jaser, N., Lallukka, S., Käkelä, P., Venesmaa, S., Simonen, M., Saltevo, J., Moilanen, L., Korpi-Hyövalti, E., Keinänen-Kiukaanniemi, S., Oksa, H., Orho-Melander, M., Valenti, L., ... Yki-Järvinen, H. (2014). A population-based study on the prevalence of NASH using scores validated against liver histology. Journal of Hepatology, 60(4), 839-846. https://doi.org/10.1016/j.jhep.2013.12.009