title: Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management.
abstract: OBJECTIVE
  There remains uncertainty about the natural history of non-alcoholic fatty liver disease (NAFLD). The spectrum of NAFLD includes non-alcoholic fatty liver (NAFL; steatosis without hepatocellular injury) and steatohepatitis (NASH; steatosis with hepatocyte ballooning degeneration±fibrosis). Our aim was to assess the histological severity of NAFLD in a cohort with serial biopsy data, and determine factors predicting progression.
  
  
  METHODS
  Patients with two liver biopsies more than a year apart were identified. Clinical and laboratory data were collected from the time of liver biopsy.
  
  
  RESULTS
  108 patients had serial biopsies (median interval 6.6years, range 1.3-22.6). 81 (75%) patients had NASH and 27 had NAFL. Overall, 45 (42%) patients had fibrosis progression, 43 (40%) had no change in fibrosis, while 20 (18%) had fibrosis regression. Importantly, no significant difference in the proportion exhibiting fibrosis progression was found between those with NAFL or NASH at index biopsy (37% vs. 43%, p=0.65). Progression to NASH was seen in 44% of patients with baseline NAFL. Of 10 patients with NAFL who had fibrosis progression, 3 progressed by 1 stage, 5 by 2 stages and 2 by 3 stages; all had NASH on follow-up biopsy. Of concern, 6 of 27 (22%) patients with baseline NAFL, reached stage 3 fibrosis at follow-up biopsy. Among the patients with NAFL, 80% of those having fibrosis progression were diabetic at the follow-up liver biopsy compared with 25% of non-progressors (p=0.005).
  
  
  CONCLUSIONS
  Contrary to current dogma, this study suggests that steatosis can progress to NASH and clinically significant fibrosis.
authors.affiliation: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, United Kingdom. Electronic address: stuart.mcpherson@nuth.nhs.uk.
authors.forename: Stuart
authors.initials: S
authors.lastname: McPherson
authors.affiliation: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Tim
authors.initials: T
authors.lastname: Hardy
authors.affiliation: Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, United Kingdom.
authors.forename: Elsbeth
authors.initials: E
authors.lastname: Henderson
authors.affiliation: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, United Kingdom.
authors.forename: Alastair D
authors.initials: AD
authors.lastname: Burt
authors.affiliation: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, United Kingdom.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Day
authors.affiliation: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, United Kingdom.
authors.forename: Quentin M
authors.initials: QM
authors.lastname: Anstee
mesh_terms: D000328:Adult; D001706:Biopsy / Q000379:methods; D018450:Disease Progression; D005234:Fatty Liver / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology; D012307:Risk Factors; D012720:Severity of Illness Index; D006113:United Kingdom
keywords: Cirrhosis; Fibrosis; NAFLD; NASH; Steatohepatitis