title: The independent predictors of non-alcoholic steatohepatitis and its individual histological features.: Insulin resistance, serum uric acid, metabolic syndrome, alanine aminotransferase and serum total cholesterol are a clue to pathogenesis and candidate targets for treatment.
abstract: OBJECTIVE
  The diagnosis of non-alcoholic steatohepatitis (NASH) is based on the individual histological features: steatosis, lobular inflammation and ballooning. Non-alcoholic fatty liver disease (NAFLD) activity score (NAS ≥ 5) is used in clinical trials. Fibrosis dictates long-term NAFLD prognosis. Recently, more-than-mild portal inflammation has raised interest as a marker of NAFLD severity. We assessed the independent predictors of: (I) individual histological lesions of NASH; (II) diagnosis of NASH; (III) significant (stage ≥2) and advanced (stage ≥3) fibrosis; and (IV) more-than-mild portal inflammation.
  
  
  METHODS
  Data from 118 consecutive biopsy-proven NAFLD patients observed at our institution were retrospectively analyzed.
  
  
  RESULTS
  At stepwise multivariate logistic regression analyses, independent predictors were as follows. For the individual histological features of NASH: insulin resistance (IR), assessed with Homeostasis Model Assessment-IR (HOMA-IR), serum uric acid (SUA) and serum total cholesterol (TCH) for moderate-to-severe steatosis; waist circumference (waist), HOMA-IR and TCH for lobular inflammation; waist, HOMA-IR, metabolic syndrome (MS), serum alanine aminotransferase (ALT), SUA and TCH for ballooning. For NASH diagnosis: waist, HOMA-IR, MS, ALT, SUA and TCH (Brunt et al.'s classification); ALT, SUA and TCH for NAS ≥ 5. For significant and advanced fibrosis, respectively: waist, MS and ALT; age, platelets, HOMA-IR, diabetes and TCH. For more-than-mild portal inflammation: serum aspartate aminotransferase (AST), serum iron, NAS ≥ 5 and significant liver fibrosis.
  
  
  CONCLUSIONS
  HOMA-IR, SUA, MS, ALT and TCH are independent predictors of NASH and its individual histological lesions, notably including fibrosis. Based on our findings, these factors should be considered major pathogenic drivers of NASH and, by inference, potential targets for treatment.
authors.affiliation: Internal Medicine, Pavullo Hospital, Azienda USL, Modena, Italy. s.ballestri@ausl.mo.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ballestri
authors.affiliation: Internal Medicine, NOCSAE Baggiovara, Azienda USL, Modena, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Nascimbeni
authors.affiliation: Internal Medicine, NOCSAE Baggiovara, Azienda USL, Modena, Italy.|Outpatient Liver Clinic and Internal Medicine, NOCSAE, Baggiovara, Azienda USL, Modena, Italy.
authors.forename: Dante
authors.initials: D
authors.lastname: Romagnoli
authors.affiliation: Internal Medicine, NOCSAE Baggiovara, Azienda USL, Modena, Italy.|Outpatient Liver Clinic and Internal Medicine, NOCSAE, Baggiovara, Azienda USL, Modena, Italy.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Lonardo
keywords: HOMA-IR; NAFLD; fibrosis; inflammatory grading; iron; steatosis