Lipid profiling of pre-treatment liver biopsy tissue predicts sustained virological response in patients with chronic hepatitis C
File(s)Rifaximin Study_Final.docx (491.03 KB)
Accepted version
Author(s)
Type
Journal Article
Abstract
Aim: 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 (1H 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 1H 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.
Methods: Baseline liver biopsy samples from 31 patients with chronic hepatitis C were analyzed histologically and by 1H 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.
Date Issued
2012-06-12
Date Acceptance
2012-01-16
Citation
Hepatology Research, 2012, 42 (7), pp.714-720
ISSN
1386-6346
Publisher
Wiley
Start Page
714
End Page
720
Journal / Book Title
Hepatology Research
Volume
42
Issue
7
Copyright Statement
© 2012 The Japan Society of Hepatology. This is the peer reviewed version of the article, which has been published in final form at https://dx.doi.org/10.1111/j.1872-034X.2012.00975.x. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000305128600011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Gastroenterology & Hepatology
hepatitis C
lipid
liver
magnetic resonance spectroscopy
steatosis
sustained virological response
SPINNING H-1-NMR SPECTROSCOPY
ALPHA-2A PLUS RIBAVIRIN
INSULIN-RESISTANCE
ANTIVIRAL THERAPY
OXIDATIVE STRESS
VIRUS-INFECTION
STEATOSIS
SUPPRESSOR
EXPRESSION
DISEASE
Publication Status
Published