title: Dual-photon microscopy-based quantitation of fibrosis-related parameters (q-FP) to model disease progression in steatohepatitis.
abstract: There is a need for further refinement of current histological systems for assessment of hepatic fibrosis in nonalcoholic fatty liver disease (NAFLD). This study evaluated hepatic fibrosis in NAFLD using dual-photon microscopy-based quantitation of fibrosis-related parameters (q-FPs). Fifty test cohort subjects and 42 validation cohort subjects with NAFLD and the full spectrum of fibrosis were studied. q-FPs were measured in specific predefined regions of interest (general, vessel, perisinusoid, and vascular septa). Seventy q-FPs had inter- and intraobserver concordance ≥0.8 and were related to the NASH Clinical Research Network fibrosis staging. Of these, 16 q-FPs with the strongest correlations (P < 0.001 for all) were entered in a principal component analysis model (odds ratio [OR] 7.8, P < 0.001), which separated any stage of fibrosis versus no fibrosis, and cirrhosis versus earlier stages with the areas under the receiver operating characteristic curves of 0.88 and 0.93 (P ≤ 0.01 for both), respectively. In an independent multivariable analysis, four q-FPs-the number of collagen strands (OR 8.5, P = 0.004), strand length (OR 12.0, P = 0.02), strand eccentricity (OR 8.3, P = 0.004), and strand solidity (OR 8.0, P = 0.003)-were independently associated with fibrosis stages and were used to model fibrosis along a continuous linear scale using desirability functions; this linear scale of fibrosis measurement was also related to fibrosis stage (P < 0.0001). The robustness of both the multivariable model and the linear scale of measurement was confirmed in the validation cohort.
  
  
  
  The q-FP model provides an accurate reproducible method to evaluate fibrosis in NAFLD along a quantitative and continuous scale. (Hepatology 2017;65:1891-1903).
authors.affiliation: Department of Infectious Diseases & Hepatology Unit, Southern Medical University Nanfang Hospital, GZ China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA.
authors.forename: Robert
authors.initials: R
authors.lastname: Vincent
authors.affiliation: Department of Infectious Diseases & Hepatology Unit, Southern Medical University Nanfang Hospital, GZ China.
authors.forename: Jinlian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA.
authors.forename: Amon
authors.initials: A
authors.lastname: Asgharpour
authors.affiliation: Department of Infectious Diseases & Hepatology Unit, Southern Medical University Nanfang Hospital, GZ China.
authors.forename: Xieer
authors.initials: X
authors.lastname: Liang
authors.affiliation: Divsion of Surgical Pathology, Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, VA.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Idowu
authors.affiliation: Divsion of Surgical Pathology, Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, VA.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Contos
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA.
authors.forename: Kalyani
authors.initials: K
authors.lastname: Daitya
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA.
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Siddiqui
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA.
authors.forename: Faridoddin
authors.initials: F
authors.lastname: Mirshahi
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA.
authors.forename: Arun J
authors.initials: AJ
authors.lastname: Sanyal
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001707:Biopsy, Needle; D015331:Cohort Studies; D018450:Disease Progression; D005234:Fatty Liver / Q000175:diagnosis / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016014:Linear Models; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000473:pathology*; D008111:Liver Function Tests; D008297:Male; D008855:Microscopy, Electron, Scanning / Q000379:methods*; D008875:Middle Aged; D015999:Multivariate Analysis; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis / Q000473:pathology*; D015588:Observer Variation; D015203:Reproducibility of Results; D012720:Severity of Illness Index