title: Digital histology quantification of intra-hepatic fat in patients undergoing liver resection.
abstract: BACKGROUND
  High intra-hepatic fat (IHF) content is associated with insulin resistance, visceral adiposity, and increased morbidity and mortality following liver resection. However, in clinical practice, IHF is assessed indirectly by pre-operative imaging [for example, chemical-shift magnetic resonance (CS-MR)]. We used the opportunity in patients undergoing liver resection to quantify IHF by digital histology (D-IHF) and relate this to CT-derived anthropometrics, insulin-related serum biomarkers, and IHF estimated by CS-MR.
  
  
  METHODS
  A reproducible method for quantification of D-IHF using 7 histology slides (inter- and intra-rater concordance: 0.97 and 0.98) was developed. In 35 patients undergoing resection for colorectal cancer metastases, we measured: CT-derived subcutaneous and visceral adipose tissue volumes, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), fasting serum adiponectin, leptin and fetuin-A. We estimated relative IHF using CS-MR and developed prediction models for IHF using a factor-clustered approach.
  
  
  RESULTS
  The multivariate linear regression models showed that D-IHF was best predicted by HOMA-IR (Beta coefficient(per doubling): 2.410, 95% CI: 1.093, 5.313) and adiponectin (β(per doubling): 0.197, 95% CI: 0.058, 0.667), but not by anthropometrics. MR-derived IHF correlated with D-IHF (rho: 0.626; p = 0.0001), but levels of agreement deviated in upper range values (CS-MR over-estimated IHF: regression versus zero, p = 0.009); this could be adjusted for by a correction factor (CF: 0.7816).
  
  
  CONCLUSIONS
  Our findings show IHF is associated with measures of insulin resistance, but not measures of visceral adiposity. CS-MR over-estimated IHF in the upper range. Larger studies are indicated to test whether a correction of imaging-derived IHF estimates is valid.
authors.affiliation: Institute of Cancer Sciences, University of Manchester, Manchester, UK; Department of Hepatobiliary Surgery, North Manchester General Hospital, Manchester, UK. Electronic address: ed.parkin@nhs.net.
authors.forename: E
authors.initials: E
authors.lastname: Parkin
authors.affiliation: Institute of Cancer Sciences, University of Manchester, Manchester, UK; Department of Hepatobiliary Surgery, North Manchester General Hospital, Manchester, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: O'Reilly
authors.affiliation: Department of Radiology, The Christie Hospital NHS Foundation Trust, Manchester, UK.
authors.forename: A A
authors.initials: AA
authors.lastname: Plumb
authors.affiliation: Department of Radiology, The Christie Hospital NHS Foundation Trust, Manchester, UK.
authors.forename: P
authors.initials: P
authors.lastname: Manoharan
authors.affiliation: Department of Histopathology, Royal Oldham Hospital, Oldham, UK.
authors.forename: M
authors.initials: M
authors.lastname: Rao
authors.affiliation: Institute of Cancer Sciences, University of Manchester, Manchester, UK; Department of Hepatobiliary Surgery, North Manchester General Hospital, Manchester, UK.
authors.forename: P
authors.initials: P
authors.lastname: Coe
authors.affiliation: Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Frystyk
authors.affiliation: Department of Hepatobiliary Surgery, North Manchester General Hospital, Manchester, UK.
authors.forename: B
authors.initials: B
authors.lastname: Ammori
authors.affiliation: Department of Hepatobiliary Surgery, North Manchester General Hospital, Manchester, UK.
authors.forename: N
authors.initials: N
authors.lastname: de Liguori Carino
authors.affiliation: Department of Hepatobiliary Surgery, North Manchester General Hospital, Manchester, UK.
authors.forename: R
authors.initials: R
authors.lastname: Deshpande
authors.affiliation: Department of Hepatobiliary Surgery, North Manchester General Hospital, Manchester, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Sherlock
authors.affiliation: Institute of Cancer Sciences, University of Manchester, Manchester, UK; Department of Colorectal Surgery, The Christie Hospital NHS Foundation Trust, Manchester, UK.
authors.forename: A G
authors.initials: AG
authors.lastname: Renehan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000473:pathology / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006498:Hepatectomy; D006801:Humans; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000000981:diagnostic imaging*; D008099:Liver / Q000000981:diagnostic imaging* / Q000601:surgery; D008113:Liver Neoplasms / Q000175:diagnosis / Q000556:secondary / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009017:Morbidity / Q000639:trends; D009765:Obesity / Q000175:diagnosis* / Q000453:epidemiology; D011183:Postoperative Complications / Q000000981:diagnostic imaging / Q000453:epidemiology*; D011446:Prospective Studies; D011859:Radiography; D015996:Survival Rate / Q000639:trends; D006113:United Kingdom / Q000453:epidemiology
keywords: Hepatic steatosis; Insulin resistance; Liver surgery; Obesity; Visceral adiposity