title: Hepatic lipid profiling in chronic hepatitis C: an in vitro and in vivo proton magnetic resonance spectroscopy study.
abstract: OBJECTIVE
  Hepatic steatosis is an important factor in pathogenesis, progression and response to treatment in hepatitis C. We aimed to investigate differences in hepatic lipid composition in liver biopsies from patients with chronic hepatitis C using proton magnetic resonance spectroscopy ((1)H MRS) and to translate these findings to the in vivo clinical setting.
  
  
  METHODS
  Two cohorts of patients with histologically defined chronic hepatitis C were studied. High-resolution MR spectra were obtained from 47 liver biopsy samples. These data were used to derive biologically relevant prior knowledge for the assignment and interpretation of lower-resolution in vivo hepatic MRS data acquired at 1.5T from a second cohort of 59 patients. MRS data were obtained both in vitro and in vivo from a subset of 11 patients.
  
  
  RESULTS
  Multivariate factor analysis demonstrated characteristic MR spectral differences by fibrosis stage and genotype. Total lipid increased with fibrosis stage (r=0.43, p=0.003) and was higher in genotype 3 compared to genotype 1 (p=0.03), while lipid polyunsaturation decreased with increasing fibrosis stage (r=-0.55, p<0.0005) and, independently, with increasing steatosis. Non-invasive assessment using in vivo hepatic (1)H MRS corroborated in vitro findings, but the signal-to-noise ratio was insufficient for reliable assessment of lipid polyunsaturation in vivo.
  
  
  CONCLUSIONS
  Hepatic lipid composition was analysed using MRS in patients with chronic hepatitis C in vitro and in vivo, demonstrating significant differences in indices by disease severity. High-resolution data informed the analysis and interpretation of in vivo spectra, but further improvements in spectral quality in vivo are required.
authors.affiliation: Department of Hepatology and Gastroenterology, Imperial College London, St. Mary's Hospital Campus, 10th Floor, QEQM Building, Praed Street, London W2 1NY, UK.
authors.forename: Jeremy F L
authors.initials: JF
authors.lastname: Cobbold
authors.forename: Jaymin H
authors.initials: JH
authors.lastname: Patel
authors.forename: Robert D
authors.initials: RD
authors.lastname: Goldin
authors.forename: Bernard V
authors.initials: BV
authors.lastname: North
authors.forename: Mary M E
authors.initials: MM
authors.lastname: Crossey
authors.forename: Julie
authors.initials: J
authors.lastname: Fitzpatrick
authors.forename: Marzena
authors.initials: M
authors.lastname: Wylezinska
authors.forename: Howard C
authors.initials: HC
authors.lastname: Thomas
authors.forename: I Jane
authors.initials: IJ
authors.lastname: Cox
authors.forename: Simon D
authors.initials: SD
authors.lastname: Taylor-Robinson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D015331:Cohort Studies; D005260:Female; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011522:Protons; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D008055:Lipids; D011522:Protons