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Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis
Lipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 (HCV-G3) infection is an independent risk factor for hepa...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975940/ https://www.ncbi.nlm.nih.gov/pubmed/35365728 http://dx.doi.org/10.1038/s41598-022-09588-w |
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author | Sheridan, David A. Shawa, Isaac Thom Thomas, E. Louise Felmlee, Daniel J. Bridge, Simon H. Neely, Dermot Cobbold, Jeremy F. Holmes, Elaine Bassendine, Margaret F. Taylor-Robinson, Simon D. |
author_facet | Sheridan, David A. Shawa, Isaac Thom Thomas, E. Louise Felmlee, Daniel J. Bridge, Simon H. Neely, Dermot Cobbold, Jeremy F. Holmes, Elaine Bassendine, Margaret F. Taylor-Robinson, Simon D. |
author_sort | Sheridan, David A. |
collection | PubMed |
description | Lipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 (HCV-G3) infection is an independent risk factor for hepatocellular carcinoma and evidence suggests lipogenic proteins are involved in hepatocarcinogenesis. We aimed to characterise variation in host lipid metabolism between participants chronically infected with HCV genotype 1 (HCV-G1) and HCV-G3 to identify likely genotype-specific differences in lipid metabolism. We combined several lipidomic approaches: analysis was performed between participants infected with HCV-G1 and HCV-G3, both in the fasting and non-fasting states, and after sustained virological response (SVR) to treatment. Sera were obtained from 112 fasting patients (25% with cirrhosis). Serum lipids were measured using standard enzymatic methods. Lathosterol and desmosterol were measured by gas-chromatography mass spectrometry (MS). For further metabolic insight on lipid metabolism, ultra-performance liquid chromatography MS was performed on all samples. A subgroup of 13 participants had whole body fat distribution determined using in vivo magnetic resonance imaging and spectroscopy. A second cohort of (non-fasting) sera were obtained from HCV Research UK for comparative analyses: 150 treatment naïve patients and 100 non-viraemic patients post-SVR. HCV-G3 patients had significantly decreased serum apoB, non-HDL cholesterol concentrations, and more hepatic steatosis than those with HCV-G1. HCV-G3 patients also had significantly decreased serum levels of lathosterol, without significant reductions in desmosterol. Lipidomic analysis showed lipid species associated with reverse cholesterol transport pathway in HCV-G3. We demonstrated that compared to HCV-G1, HCV-G3 infection is characterised by low LDL cholesterol levels, with preferential suppression of cholesterol synthesis via lathosterol, associated with increasing hepatic steatosis. The genotype-specific lipid disturbances may shed light on genotypic variations in liver disease progression and promotion of hepatocellular cancer in HCV-G3. |
format | Online Article Text |
id | pubmed-8975940 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-89759402022-04-05 Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis Sheridan, David A. Shawa, Isaac Thom Thomas, E. Louise Felmlee, Daniel J. Bridge, Simon H. Neely, Dermot Cobbold, Jeremy F. Holmes, Elaine Bassendine, Margaret F. Taylor-Robinson, Simon D. Sci Rep Article Lipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 (HCV-G3) infection is an independent risk factor for hepatocellular carcinoma and evidence suggests lipogenic proteins are involved in hepatocarcinogenesis. We aimed to characterise variation in host lipid metabolism between participants chronically infected with HCV genotype 1 (HCV-G1) and HCV-G3 to identify likely genotype-specific differences in lipid metabolism. We combined several lipidomic approaches: analysis was performed between participants infected with HCV-G1 and HCV-G3, both in the fasting and non-fasting states, and after sustained virological response (SVR) to treatment. Sera were obtained from 112 fasting patients (25% with cirrhosis). Serum lipids were measured using standard enzymatic methods. Lathosterol and desmosterol were measured by gas-chromatography mass spectrometry (MS). For further metabolic insight on lipid metabolism, ultra-performance liquid chromatography MS was performed on all samples. A subgroup of 13 participants had whole body fat distribution determined using in vivo magnetic resonance imaging and spectroscopy. A second cohort of (non-fasting) sera were obtained from HCV Research UK for comparative analyses: 150 treatment naïve patients and 100 non-viraemic patients post-SVR. HCV-G3 patients had significantly decreased serum apoB, non-HDL cholesterol concentrations, and more hepatic steatosis than those with HCV-G1. HCV-G3 patients also had significantly decreased serum levels of lathosterol, without significant reductions in desmosterol. Lipidomic analysis showed lipid species associated with reverse cholesterol transport pathway in HCV-G3. We demonstrated that compared to HCV-G1, HCV-G3 infection is characterised by low LDL cholesterol levels, with preferential suppression of cholesterol synthesis via lathosterol, associated with increasing hepatic steatosis. The genotype-specific lipid disturbances may shed light on genotypic variations in liver disease progression and promotion of hepatocellular cancer in HCV-G3. Nature Publishing Group UK 2022-04-01 /pmc/articles/PMC8975940/ /pubmed/35365728 http://dx.doi.org/10.1038/s41598-022-09588-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Sheridan, David A. Shawa, Isaac Thom Thomas, E. Louise Felmlee, Daniel J. Bridge, Simon H. Neely, Dermot Cobbold, Jeremy F. Holmes, Elaine Bassendine, Margaret F. Taylor-Robinson, Simon D. Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis |
title | Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis |
title_full | Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis |
title_fullStr | Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis |
title_full_unstemmed | Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis |
title_short | Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis |
title_sort | infection with the hepatitis c virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975940/ https://www.ncbi.nlm.nih.gov/pubmed/35365728 http://dx.doi.org/10.1038/s41598-022-09588-w |
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