title: Are simple noninvasive scoring systems for fibrosis reliable in patients with NAFLD and normal ALT levels?
abstract: BACKGROUND
  Nonalcoholic fatty liver disease (NAFLD) is common and many affected individuals have normal-range alanine aminotransferase (ALT) levels. There is a need for a robust screening tool to triage individuals with advanced fibrosis for specialist care.
  
  
  OBJECTIVE
  The aim of this study was to assess the performance of noninvasive fibrosis tests in patients with biopsy-proven NAFLD and normal levels of ALT.
  
  
  METHODS
  Patients presenting at a fatty liver clinic between 1999 and 2009 were included in the study. Liver biopsies were assessed using the Kleiner score. The aspartate aminotransferase (AST)/ALT ratio, BARD, FIB-4 and NAFLD fibrosis scores were calculated.
  
  
  RESULTS
  A total of 305 patients were included [70 with normal ALT levels (women: ALT≤30 IU/l, men: ALT≤45 IU/l) and 235 with elevated levels]. In total, 24% of patients with normal ALT levels and 17% of those with elevated ALT levels had advanced fibrosis (Kleiner stage 3-4). The FIB-4 performed best in identifying advanced fibrosis in patients with normal ALT (area under receiver operating characteristic curve=0.86, 82% sensitivity, 77% specificity and 92% negative predictive value). The sensitivity of the AST/ALT ratio and BARD and NAFLD fibrosis scores for advanced fibrosis was good in patients with normal ALT levels (94, 94 and 82%, respectively), but the specificity was low (44, 26 and 51%, respectively). The FIB-4 yielded best results in patients with elevated ALT levels. Using the FIB-4, 61% of patients with normal ALT levels and 63% of those with elevated ALT levels could avoid liver biopsy to exclude advanced fibrosis. In contrast, AST/ALT ratio and BARD and NAFLD scores would have led to a high proportion of patients with mild disease having to undergo a biopsy.
  
  
  CONCLUSIONS
  The FIB-4 yielded good results in patients with normal or elevated ALT levels, reliably excluding advanced fibrosis and reducing the need for liver biopsy.
authors: Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle University, Newcastle Upon Tyne, UK. stuart.mcpherson@nuth.nhs.uk
authors: Stuart
authors: S
authors: McPherson
authors: Quentin M
authors: QM
authors: Anstee
authors: Elsbeth
authors: E
authors: Henderson
authors: Christopher P
authors: CP
authors: Day
authors: Alastair D
authors: AD
authors: Burt
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D005234:Fatty Liver / Q000150:complications* / Q000473:pathology; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D012016:Reference Values; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D014218:Triage
chemical_list: D015415:Biomarkers; D000410:Alanine Transaminase