title: NASH and cryptogenic cirrhosis: a histological analysis.
abstract: BACKGROUND
  Epidemiological studies indicate that nonalcoholic steatohepatitis (NASH) is a common cause of cirrhosis described as 'cryptogenic'. To address this from a histological perspective and to examine the significance of residual histological findings as an indication of prior NASH, we looked back at biopsies in patients who presented with cirrhosis without sufficient histological features to diagnose NASH but who had prior histologically confirmed non-cirrhotic NASH.
  
  
  METHODS
  Seven patients were identified with biopsy pairs showing non-specific (cryptogenic) cirrhosis in the latest specimen and a prior biopsy showing non-cirrhotic NASH. Using an expanded NASH-CRN system scored blindly by light microscopy, we compared the early and late biopsies to each other and to a cohort of 13 patients with cirrhosis due to hepatitis C without co-existing metabolic syndrome.
  
  
  RESULTS
  Macrosteatosis, although uniformly present in the non-cirrhotic NASH specimens, declined in the late stage cirrhotic NASH specimens and was not useful in the distinction of late cirrhotic NASH from cirrhotic viral hepatitis. However, the presence of ballooned cells, Mallory-Denk bodies, and megamitochondria and the absence of apoptotic bodies were significantly different in late stage cirrhotic NASH compared to cirrhosis due to hepatitis C.
  
  
  CONCLUSIONS
  Histologically advanced NASH presenting as non-specific or cryptogenic cirrhosis has residual changes which are consistent with prior steatohepatitis but which differ from cirrhosis due to hepatitis C. These results provide histological support for the more established epidemiological associations of NASH with cryptogenic cirrhosis and for criteria used in several proposed classifications of cryptogenic cirrhosis.
authors.affiliation: Division of Gastroenterology and Hepatology, Digestive Health Center, University of Virginia, Charlottesville, Virginia 22908, USA. shc5c@virginia.edu
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Caldwell
authors.forename: Vanessa D
authors.initials: VD
authors.lastname: Lee
authors.forename: David E
authors.initials: DE
authors.lastname: Kleiner
authors.forename: Abdullah M S
authors.initials: AM
authors.lastname: Al-Osaimi
authors.forename: Curtis K
authors.initials: CK
authors.lastname: Argo
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Northup
authors.forename: Carl L
authors.initials: CL
authors.lastname: Berg
mesh_terms: D000328:Adult; D017209:Apoptosis; D001706:Biopsy; D003937:Diagnosis, Differential; D018450:Disease Progression; D005234:Fatty Liver / Q000150:complications* / Q000175:diagnosis / Q000473:pathology*; D005260:Female; D006526:Hepatitis C / Q000150:complications / Q000175:diagnosis / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000473:pathology