title: Portal chronic inflammation in nonalcoholic fatty liver disease (NAFLD): a histologic marker of advanced NAFLD-Clinicopathologic correlations from the nonalcoholic steatohepatitis clinical research network.
abstract: Adult nonalcoholic fatty liver disease (NAFLD) is characterized by absent or mild portal chronic inflammation (CI); in children, portal CI may be predominant. This study correlated clinical features with portal CI. Centrally-graded biopsies and temporally-related clinical parameters from 728 adults and 205 children. From the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) were evaluated. Mild, more than mild and no portal CI were found in 60%, 23% and 16% of adult biopsies and 76%, 14% and 10% of pediatric biopsies. Autoantibodies, and elevated alanine aminotransferase were not associated with portal CI. Clinical features associated with "more than mild" in adults were older age (P < 0.0001), female gender (P = 0.001), higher body mass index (P < 0.0001), elevated insulin levels (P = 0.001), higher homeostasis model assessment of insulin resistance score (HOMA-IR) (P < 0.0001), and medications used for NAFLD (P = 0.0004), diabetes (P < 0.0001), and hypertension (P < 0.0001). "More than mild" in the pediatric biopsies correlated with younger age (P = 0.01), but not with body mass index, insulin or HOMA-IR. In both groups, lobular and portal inflammation scores had no association, but there was an association with definite steatohepatitis (P < 0.0001). Features associated in the adult biopsies with "more than mild" were steatosis amount (P = 0.01) and location (P < 0.0001), ballooning (P < 0.0001), and advanced fibrosis (P < 0.0001). In the pediatric biopsies, "more than mild" was associated with steatosis location (P = 0.0008) and fibrosis score (P < 0.0001), specifically, the portal/periportal fibrosis or greater fibrosis) (P < 0.01).
  
  
  CONCLUSIONS
  Increased portal CI is associated with many clinical and pathologic features of progressive NAFLD in both adults and children, but not with ALT, autoantibodies, or lobular inflammation. More than mild portal CI in liver biopsies of untreated NAFLD may be considered a marker of advanced disease.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Brunt
authors.forename: David E
authors.initials: DE
authors.lastname: Kleiner
authors.forename: Laura A
authors.initials: LA
authors.lastname: Wilson
authors.forename: Aynur
authors.initials: A
authors.lastname: Unalp
authors.forename: Cynthia E
authors.initials: CE
authors.lastname: Behling
authors.forename: Joel E
authors.initials: JE
authors.lastname: Lavine
authors.forename: Brent A
authors.initials: BA
authors.lastname: Neuschwander-Tetri
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood; D001706:Biopsy; D002648:Child; D002908:Chronic Disease; D018450:Disease Progression; D005234:Fatty Liver / Q000097:blood / Q000473:pathology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000473:pathology; D008099:Liver / Q000473:pathology*; D008107:Liver Diseases / Q000097:blood / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012737:Sex Factors
chemical_list: D000410:Alanine Transaminase