Hepatic lipid profiling in chronic hepatitis C: An in vitro and in vivo proton magnetic resonance spectroscopy study

Background & Aims: 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 (H-1 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 1.5 T 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 H-1 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. (C) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.