title: Clinical spectrum of non-alcoholic fatty liver disease in diabetic and non-diabetic patients.
abstract: BACKGROUND
  While non-alcoholic fatty liver disease (NAFLD) has been well characterised in patients with diabetes mellitus (DM), less is known about NAFLD in non-DM patients. We investigated the clinical characteristics of NAFLD patients with and without DM and accuracy of the NAFLD fibrosis score (NFS) in these two NAFLD groups.
  
  
  METHODS
  Clinical, biochemical and histological variables were evaluated in this prospective cross-sectional study of 503 patients with biopsy proven NAFLD. Comparisons between patients with and without DM were analysed. NFS was correlated with liver histology to assess its robustness in patients with and without DM.
  
  
  RESULTS
  There were 503 biopsy proven NAFLD patients with 48% of the cohort being diabetic. Relative to patients without DM, patients with DM were older (52 vs. 46 years, p < 0.001), with higher proportion of females (70% vs. 54%, p < 0.001), higher BMI (37 vs. 35, p = 0.009), higher prevalence of hypertension (73% vs. 44%, p < 0.001), higher prevalence of NASH (80.2% vs. 64.4%; p < 0.001) and advanced fibrosis (40.3% vs. 17.0%; p < 0.001). A considerable amount of patients without DM still had NASH (64%) and advanced fibrosis (17%). The clinical utility of the NFS differed between NAFLD patients with and without DM, with sensitivity to exclude advanced fibrosis being 90% of NAFLD patients with DM but only 58% of patients without DM.
  
  
  CONCLUSIONS
  Patients with DM have more severe NAFLD based on histology. However, NASH and advanced fibrosis also occur in a considerable proportion of NAFLD patients without DM. The lower utility of the NFS in NAFLD patients without DM emphasises the heterogeneous nature of the NAFLD phenotype.
authors.affiliation: Department of Gastroenterology at Cleveland Clinic, USA.
authors.forename: George Boon-Bee
authors.initials: GB
authors.lastname: Goh
authors.affiliation: Department of Gastroenterology at Cleveland Clinic, USA.
authors.forename: Mangesh R
authors.initials: MR
authors.lastname: Pagadala
authors.affiliation: Department of Family Medicine at MetroHealth Medical Center, USA.
authors.forename: Jaividhya
authors.initials: J
authors.lastname: Dasarathy
authors.affiliation: Department of Public Health at Johns Hopkins University, USA.
authors.forename: Aynur
authors.initials: A
authors.lastname: Unalp-Arida
authors.affiliation: Department of Gastroenterology at Cleveland Clinic, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Sargent
authors.affiliation: Department of MetroHealth Medical Center, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Hawkins
authors.affiliation: Department of Gastroenterology at Cleveland Clinic, USA.
authors.forename: Achuthan
authors.initials: A
authors.lastname: Sourianarayanane
authors.affiliation: Department of MetroHealth Medical Center, USA.
authors.forename: Amer
authors.initials: A
authors.lastname: Khiyami
authors.affiliation: Department of Pathology at Cleveland Clinic, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Yerian
authors.affiliation: Department of Pathology at Cleveland Clinic, USA.
authors.forename: Rish K
authors.initials: RK
authors.lastname: Pai
authors.affiliation: Department of Gastroenterology at Cleveland Clinic, USA ; Department of Pathobiology at Cleveland Clinic, USA.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Dasarathy
authors.affiliation: Department of Gastroenterology at Cleveland Clinic, USA ; Department of Pathobiology at Cleveland Clinic, USA.
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: McCullough
keywords: ACE-I, angiotensin-converting enzyme-inhibitor; ALP, alkaline phosphatase; ALT, alanine aminotransferase; ARB, angiotensin receptor blocker; AST, aspartate aminotransferase; BMI, body mass index; CIs, confidence intervals; Chol, total cholesterol; DM, type 2 diabetes mellitus; Diabetic; ER, endoplasmic reticulum; FFAs, free-fatty acids; HDL, high density lipoprotein cholesterol; HOMA-IR, Homeostatic model assessment—insulin resistance; INR, international normalised ratio; LDL, low density lipoprotein cholesterol; NAFLD; NAFLD fibrosis score; NAFLD, non-alcoholic fatty liver disease; NAS, NAFLD activity score; NASH CRN, Non-alcoholic Steatohepatitis Clinical Research Network; NASH, non-alcoholic steatohepatitis; NFS, NAFLD fibrosis score; Non-diabetic; ORs, odd ratios; SDs, standard deviations; TGs, triglycerides; VLDL, very-low-density lipoproteins; apoB-100, apolipoprotein B-100