Lipid profiling of pre-treatment liver biopsy tissue predicts sustained virological response in patients with chronic hepatitis C.
OBJECTIVE
Hepatic lipid is important in the pathogenesis and progression of hepatitis C-related liver disease. Polyunsaturated fatty acids have been shown to reduce viral replication in cell culture. Proton magic angle spinning magnetic resonance spectroscopy ((1) H MAS MRS) enables metabolic analysis of intact tissue. The aim was to examine the relationship between hepatic lipid composition by metabolic profiling of liver tissue at baseline and treatment response to pegylated-Interferon alfa2 and Ribavirin.


METHODS
Baseline liver biopsy samples from 31 patients with chronic hepatitis C were analyzed histologically and by (1) H MAS MRS. Indices of lipid composition were derived and partial least squares discriminant analysis with cross-validation was used to predict treatment outcome.


RESULTS
Of 31 patients, 14 achieved sustained virological response (SVR). Lipid polyunsaturation (median (IQR)) was higher in SVR (3.41% (2.31)) than in treatment failure (TF) (2.15% (1.51)), P = 0.02. Lipid saturation was lower in SVR (85.9% (3.39)) than TF (86.7% (2.17)), P = 0.04. The total lipid content was lower in SVR (1.54% (0.81)) than TF (2.72% (3.47)), P = 0.004. Total choline to lipid ratio was higher in SVR (11.51% (9.99)) than TF (7.5% (6.82)), P = 0.007. Cross-validation correctly predicted the SVR group in 13 of 14 samples with 1 sample misclassified, and the TF group in all 17 samples.


CONCLUSIONS
Lipid polyunsaturation was greater and total lipid lower in those with SVR, compared with TF. Metabolic profiling of intact liver biopsy samples predicted SVR with high accuracy. Hepatic lipid composition may impact on treatment success.
Hepatology and Gastroenterology Section             Imaging Sciences Department             Department of Histopathology, Imperial College London, London, UK.
Jeremy F L
JF
Cobbold
I Jane
IJ
Cox
Ashley S
AS
Brown
Horace R T
HR
Williams
Robert D
RD
Goldin
Howard C
HC
Thomas
Mark R
MR
Thursz
Simon D
SD
Taylor-Robinson