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Desrochers GF, Filip R, Bastianelli M, Stern T, Pezacki JP. microRNA-27b regulates hepatic lipase enzyme LIPC and reduces triglyceride degradation during hepatitis C virus infection. J Biol Chem 2022; 298:101983. [PMID: 35483451 PMCID: PMC9163519 DOI: 10.1016/j.jbc.2022.101983] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 03/24/2022] [Accepted: 03/26/2022] [Indexed: 11/26/2022] Open
Abstract
miRNAs are short, noncoding RNAs that negatively and specifically regulate protein expression, the cumulative effects of which can result in broad changes to cell systems and architecture. The miRNA miR-27b is known to regulate lipid regulatory pathways in the human liver and is also induced by the hepatitis C virus (HCV). However, the functional targets of miR-27b are not well established. Herein, an activity-based protein profiling method using a serine hydrolase probe, coupled with stable isotope labeling and mass spectrometry identified direct and indirect targets of miR-27b. The hepatic lipase C (LIPC) stood out as both highly dependent on miR-27b and as a major modulator of lipid pathway misregulation. Modulation of miR-27b using both exogenous miRNA mimics and inhibitors demonstrated that transcription factors Jun, PPARα, and HNF4α, all of which also influence LIPC levels and activity, are regulated by miR-27b. LIPC was furthermore shown to affect the progress of the life cycle of HCV and to decrease levels of intracellular triglycerides, upon which HCV is known to depend. In summary, this work has demonstrated that miR-27b mediates HCV infection by downregulating LIPC, thereby reducing triglyceride degradation, which in turn increases cellular lipid levels.
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Affiliation(s)
| | - Roxana Filip
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada
| | - Micheal Bastianelli
- Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada
| | - Tiffany Stern
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada
| | - John Paul Pezacki
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada.
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Filip R, Desrochers GF, Lefebvre DM, Reed A, Singaravelu R, Cravatt BF, Pezacki JP. Profiling of MicroRNA Targets Using Activity-Based Protein Profiling: Linking Enzyme Activity to MicroRNA-185 Function. Cell Chem Biol 2021; 28:202-212.e6. [PMID: 33450181 DOI: 10.1016/j.chembiol.2020.12.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 11/06/2020] [Accepted: 12/18/2020] [Indexed: 02/08/2023]
Abstract
MicroRNAs (miRNAs) act as cellular signal transducers through repression of protein translation. Elucidating targets using bioinformatics and traditional quantitation methods is often insufficient to uncover global miRNA function. Herein, alteration of protein function caused by miRNA-185 (miR-185), an immunometabolic miRNA, was determined using activity-based protein profiling, transcriptomics, and lipidomics. Fluorophosphonate-based activity-based protein profiling of miR-185-induced changes to human liver cells revealed that exclusively metabolic serine hydrolase enzymes were regulated in activity, some with roles in lipid and endocannabinoid metabolism. Lipidomic analysis linked enzymatic changes to levels of cellular lipid species, such as components of very-low-density lipoprotein particles. Additionally, inhibition of one miR-185 target, monoglyceride lipase, led to decreased hepatitis C virus levels in an infectious model. Overall, the approaches used here were able to identify key functional changes in serine hydrolases caused by miR-185 that are targetable pharmacologically, such that a small molecule inhibitor can recapitulate the miRNA phenotype.
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Affiliation(s)
- Roxana Filip
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa K1N 6N5, Canada
| | - Geneviève F Desrochers
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa K1N 6N5, Canada
| | - David M Lefebvre
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa K1N 6N5, Canada
| | - Alex Reed
- Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
| | - Ragunath Singaravelu
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa K1N 6N5, Canada
| | - Benjamin F Cravatt
- Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
| | - John Paul Pezacki
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa K1N 6N5, Canada.
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Ichikawa T, Miyaaki H, Miuma S, Motoyoshi Y, Narita S, Toda S, Takahashi Y, Honda T, Yajima H, Uehara R, Hino N, Hori T, Hirata R, Taura N, Nakao K. Carotid Intima-media Thickness and Small Dense Low-density Lipoprotein Cholesterol Increase after One Year of Treatment with Direct-acting Antivirals in Patients with Hepatitis C Virus Infection. Intern Med 2019; 58:1209-1215. [PMID: 30626818 PMCID: PMC6543209 DOI: 10.2169/internalmedicine.1514-18] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Objective Direct-acting antivirals (DAAs) for treating hepatitis C virus (HCV) infection exert a significantly high sustained viral response (SVR), and patients experience a rebound increase in low-density lipoprotein cholesterol (LDL) and total cholesterol levels. Carotid intima-media thickness (IMT) is a highly reproducible and non-invasive parameter for assessing the atherosclerotic process, and the small dense (sd) LDL level is useful for clinically evaluating the atherogenic risk. Methods A total of 48 patients with chronic HCV infection were treated with DAAs. All patients exhibited an SVR 24 weeks later. We compared the metabolic profiles of the patients, including the sdLDL and IMT values, at the start of DAA treatment with those after one year of treatment. We verified whether the HCV clearance after the administration of DAAs is associated with the development of atherosclerosis. Results The sdLDL, %sdLDL (sdLDL/LDL), and LDL values were exacerbated after a year of treatment; however, the triglyceride level, glycated hemoglobin level, insulin resistance, and body weight remained unaltered. The max-IMT was increased after a year compared to that at the start of treatment. Differences in the max-IMT (dmax-IMT) were greater in men than in women; however, no correlation was observed between the dmax-IMT and genotype, fibrosis, hypertension, hyperlipidemia, diabetes, obesity, and dialysis status. The %sdLDL at the start and a year later was positively correlated with the dmax-IMT. No correlation was observed among various factors including the LDL, triglyceride, body mass index, insulin resistance and dmax-IMT. In uni- and multivariate analyses, a significant correlation was observed between %sdLDL≥16% at the start of treatment and the sex and dmax-IMT. Conclusion Because the sdLDL and IMT values were exacerbated after a year of DAA treatment, atherosclerosis must be evaluated in patients achieving an SVR.
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Affiliation(s)
- Tatsuki Ichikawa
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
- Innovation and Translational Research Center, Nagasaki Harbor Medical Center, Japan
- Department of Comprehensive Community Care Systems, Graduate School of Biomedical Sciences, Nagasaki University, Japan
| | - Hisamitsu Miyaaki
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Sciences, Nagasaki University, Japan
| | - Satoshi Miuma
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Sciences, Nagasaki University, Japan
| | | | - Syouhei Narita
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
| | - Satomi Toda
- Innovation and Translational Research Center, Nagasaki Harbor Medical Center, Japan
| | - Youichi Takahashi
- Innovation and Translational Research Center, Nagasaki Harbor Medical Center, Japan
| | - Tetsurou Honda
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
| | - Hiroyuki Yajima
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
| | - Ryouhei Uehara
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
| | - Naoyuki Hino
- Department of Comprehensive Community Care Systems, Graduate School of Biomedical Sciences, Nagasaki University, Japan
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Sciences, Nagasaki University, Japan
| | - Tomoko Hori
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
| | - Ryousuke Hirata
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
| | - Naota Taura
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Sciences, Nagasaki University, Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Sciences, Nagasaki University, Japan
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Valkov I, Ivanova R, Alexiev A, Antonov K, Mateva L. Association of Serum Lipids with Hepatic Steatosis, Stage of Liver Fibrosis and Viral Load in Chronic Hepatitis C. J Clin Diagn Res 2017; 11:OC15-OC20. [PMID: 28969178 DOI: 10.7860/jcdr/2017/28609.10459] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2017] [Accepted: 06/19/2017] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Hepatitis C Virus (HCV) relies on host lipids for its life cycle contributing to lipid abnormalities and hepatic steatosis. Disease progression is influenced by viral factors interacting with host immune and metabolic pathways. The significance of serum lipids for Chronic Hepatitis C (CHC) assessment is not clearly established yet. AIM Our aim was to investigate serum lipids' association with stage of liver fibrosis, steatosis and genotypes in patients with CHC. MATERIALS AND METHODS A total of 112 CHC patients (54 male, 58 female, aged 48.6±13.7 years) were studied - 98 genotype 1 (G1) and 14 genotype 3 (G3). Liver cirrhosis (F4) was diagnosed in 31 cases. Steatosis was present in 75 of all patients on ultrasound. Liver biopsy was done in 65 patients and histology showed steatosis in 28, stages of fibrosis (F1-F3) in 56 and F4 in 9 patients (METAVIR). Laboratory panel included complete blood count, liver tests and serum lipid levels (mmol/l) with Friedewald equation estimations. Indirect noninvasive fibrosis scores FIB-4, Aspartate aminotransferase to Platelet Ratio Index (APRI) and Forns index were calculated. HCV RNA was quantified by RT-PCR. Statistical analysis included Spearman's rho, Mann-Whitney U test, Receiver Operating Characteristic (ROC) curve. RESULTS Total Cholesterol (TCh) (p=0.002) and Low-Density Lipoprotein (LDL) (p=0.003) in G1 patients were higher when steatosis was present. TCh (p<0.001), High-Density Lipoprotein (HDL) (p=0.018) and LDL (p=0.003) were lower in G1 F4 compared with F1-F3 patients. Triglyceride (TG) levels correlated with FIB-4 (r=0.364, p=0.029), APRI (r=0.333, p=0.047) and Forns index (r=0.423, p=0.010) in G1 patients without steatosis. TG to LDL ratio (TG/LDL) (p=0.001) was higher in F4 than in F1-F3 patients. TG/LDL ratio predicted the presence of F4 in G1 patients without steatosis by an area under the ROC curve 0.900 (p<0.001). TG/LDL ratio > 0.52 was highly specific for F4 without steatosis. Specificity dropped to 76% when steatosis was present. TG/LDL < 0.32 negatively predicted liver cirrhosis. HCV RNA correlated with TG levels (r=0.330, p=0.009) in G1 patients with steatosis and with histological percent of fatty hepatocytes (r=0.585, p=0.028) in G3 patients. CONCLUSION Lipid levels in CHC G1 patients depend on the presence of steatosis and cirrhosis. HCV RNA is associated with TG levels in G1 patients with steatosis, but not in G3 patients. In cirrhotic CHC G1 patients cholesterol is low with relatively increased TG. TG/LDL ratio is a potential marker of liver cirrhosis in CHC G1 patients.
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Affiliation(s)
- Ivan Valkov
- Resident and PhD Student, Clinic of Gastroenterology, University Hospital "St.Ivan Rilski", Medical University-Sofia, Bulgaria
| | - Radina Ivanova
- Associate Professor, Laboratory of Clinical Pathology, University Hospital "St.Ivan Rilski", Medical University-Sofia, Bulgaria
| | - Assen Alexiev
- Professor, Clinic of Gastroenterology, University Hospital "St.Ivan Rilski", Medical University-Sofia, Bulgaria
| | - Krasimir Antonov
- Professor, Clinic of Gastroenterology, University Hospital "St.Ivan Rilski", Medical University-Sofia, Bulgaria
| | - Lyudmila Mateva
- Professor, Head of Clinic of Gastroenterology, University Hospital "St.Ivan Rilski", Medical University-Sofia, Bulgaria
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Kinoshita C, Nagano T, Seki N, Tomita Y, Sugita T, Aida Y, Itagaki M, Satoh K, Sutoh S, Abe H, Tsubota A, Aizawa Y. Hepatitis C virus G1b infection decreases the number of small low-density lipoprotein particles. World J Gastroenterol 2016; 22:6716-6725. [PMID: 27547014 PMCID: PMC4970482 DOI: 10.3748/wjg.v22.i29.6716] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Revised: 06/11/2016] [Accepted: 07/06/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate how hepatitis C virus (HCV) G1b infection influences the particle number of lipoproteins.
METHODS: The numbers of lipoprotein particles in fasting sera from 173 Japanese subjects, 82 with active HCV G1b infection (active HCV group) and 91 with cleared HCV infection (SVR group), were examined. Serum lipoprotein was fractionated by high-performance liquid chromatography into twenty fractions. The cholesterol and triglyceride concentrations in each fraction were measured using LipoSEARCH. The number of lipoprotein particles in each fraction was calculated using a newly developed algorithm, and the relationship between chronic HCV G1b infection and the lipoprotein particle number was determined by multiple linear regression analysis.
RESULTS: The median number of low-density lipoprotein (LDL) particles was significantly lower in the active HCV group [1182 nmol/L, interquartile range (IQR): 444 nmol/L] than in the SVR group (1363 nmol/L, IQR: 472 nmol/L, P < 0.001), as was that of high-density lipoprotein (HDL) particles (14168 nmol/L vs 15054 nmol/L, IQR: 4114 nmol/L vs 3385 nmol/L, P = 0.042). The number of very low-density lipoprotein (VLDL) particles was similar between the two groups. Among the four LDL sub-fractions, the number of large LDL particles was similar between the two groups. However, the numbers of medium (median: 533.0 nmol/L, IQR: 214.7 nmol/L vs median: 633.5 nmol/L, IQR: 229.6 nmol/L, P < 0.001), small (median: 190.9 nmol/L, IQR: 152.4 nmol/L vs median: 263.2 nmol/L, IQR: 159.9 nmol/L; P < 0.001), and very small LDL particles (median: 103.5 nmol/L, IQR: 66.8 nmol/L vs median: 139.3 nmol/L, IQR: 67.3 nmol/L, P < 0.001) were significantly lower in the active HCV group than in the SVR group, respectively. Multiple linear regression analysis indicated an association between HCV G1b infection and the decreased numbers of medium, small, and very small LDL particles. However, active HCV infection did not affect the number of large LDL particles or any sub-fractions of VLDL and HDL particles.
CONCLUSION: HCV G1b infection decreases the numbers of medium, small, and very small LDL particles.
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Satoh K, Nagano T, Seki N, Tomita Y, Aida Y, Sugita T, Itagaki M, Sutoh S, Abe H, Aizawa Y. High level of serum cholesteryl ester transfer protein in active hepatitis C virus infection. World J Hepatol 2016; 8:291-300. [PMID: 26925203 PMCID: PMC4757652 DOI: 10.4254/wjh.v8.i5.291] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Revised: 10/24/2015] [Accepted: 01/29/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the significance of cholesteryl ester transfer protein (CETP) in lipoprotein abnormalities in chronic hepatitis C virus (HCV) infection.
METHODS: We evaluated the significance of the serum concentration of CETP in 110 Japanese patients with chronic HCV infection. Fifty-five patients had active HCV infection, and HCV eradication had been achieved in 55. The role of CETP in serum lipoprotein abnormalities, specifically, in triglyceride (TG) concentrations in the four major classes of lipoproteins, was investigated using Pearson correlations in conjunction with multiple regression analysis and compared them between those with active HCV infection and those in whom eradication had been achieved.
RESULTS: The serum CETP levels of patients with active HCV infection were significantly higher than those of patients in whom HCV eradication was achieved (mean ± SD, 2.84 ± 0.69 μg/mL vs 2.40 ± 1.00 μg/mL, P = 0.008). In multiple regression analysis, HCV infection status (active or eradicated) was an independent factor significantly associated with the serum CETP level. TG concentrations in low-density lipoprotein (mean ± SD, 36.25 ± 15.28 μg/mL vs 28.14 ± 9.94 μg/mL, P = 0.001) and high-density lipoprotein (HDL) (mean ± SD, 25.9 ± 7.34 μg/mL vs 17.17 ± 4.82 μg/mL, P < 0.001) were significantly higher in patients with active HCV infection than in those in whom HCV eradication was achieved. The CETP level was strongly correlated with HDL-TG in patients with active HCV infection (R = 0.557, P < 0.001), whereas CETP was not correlated with HDL-TG in patients in whom HCV eradication was achieved (R = -0.079, P = 0.56).
CONCLUSION: Our results indicate that CETP plays a role in abnormalities of lipoprotein metabolism in patients with chronic HCV infection.
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Aizawa Y, Seki N, Nagano T, Abe H. Chronic hepatitis C virus infection and lipoprotein metabolism. World J Gastroenterol 2015; 21:10299-10313. [PMID: 26420957 PMCID: PMC4579877 DOI: 10.3748/wjg.v21.i36.10299] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Revised: 07/11/2015] [Accepted: 08/31/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is a hepatotrophic virus and a major cause of chronic liver disease, including hepatocellular carcinoma, worldwide. The life cycle of HCV is closely associated with the metabolism of lipids and lipoproteins. The main function of lipoproteins is transporting lipids throughout the body. Triglycerides, free cholesterol, cholesteryl esters, and phospholipids are the major components of the transported lipids. The pathway of HCV assembly and secretion is closely linked to lipoprotein production and secretion, and the infectivity of HCV particles largely depends on the interaction of lipoproteins. Moreover, HCV entry into hepatocytes is strongly influenced by lipoproteins. The key lipoprotein molecules mediating these interactions are apolipoproteins. Apolipoproteins are amphipathic proteins on the surface of a lipoprotein particle, which help stabilize lipoprotein structure. They perform a key role in lipoprotein metabolism by serving as receptor ligands, enzyme co-factors, and lipid transport carriers. Understanding the association between the life cycle of HCV and lipoprotein metabolism is important because each step of the life cycle of HCV that is associated with lipoprotein metabolism is a potential target for anti-HCV therapy. In this article, we first concisely review the nature of lipoprotein and its metabolism to better understand the complicated interaction of HCV with lipoprotein. Then, we review the outline of the processes of HCV assembly, secretion, and entry into hepatocytes, focusing on the association with lipoproteins. Finally, we discuss the clinical aspects of disturbed lipid/lipoprotein metabolism and the significance of dyslipoproteinemia in chronic HCV infection with regard to abnormal apolipoproteins.
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Nagano T, Seki N, Tomita Y, Sugita T, Aida Y, Itagaki M, Sutoh S, Abe H, Tsubota A, Aizawa Y. Impact of Chronic Hepatitis C Virus Genotype 1b Infection on Triglyceride Concentration in Serum Lipoprotein Fractions. Int J Mol Sci 2015; 16:20576-94. [PMID: 26334270 PMCID: PMC4613219 DOI: 10.3390/ijms160920576] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Revised: 08/13/2015] [Accepted: 08/20/2015] [Indexed: 12/14/2022] Open
Abstract
Reduced low-density lipoprotein (LDL) cholesterol level is a characteristic feature of dyslipidemia in chronic hepatitis C virus (HCV) infection. However, abnormality in serum triglyceride (TG) has not been fully investigated. To clarify the impact of HCV genotype 1b (G1b) infection and advanced fibrosis on serum TG profiles, TG concentrations in lipoprotein fractions were examined in fasting sera from 185 subjects with active or cleared HCV infection by high-performance liquid chromatography. Serum lipoproteins were fractionated into four classes: chylomicron, very low-density lipoprotein (VLDL), LDL, and high-density lipoprotein (HDL). Then, the significance of HCV G1b infection on TG levels in each lipoprotein fraction was determined using multiple regression models. We found that active HCV G1b infection was positively associated with high HDL-TG levels and low VLDL-TG levels, independent of other factors included in the regression model. In VLDL sub-fractions, active HCV infection was only found to be associated with low levels of large VLDL-TG. Similarly, advanced liver fibrosis in chronic HCV G1b infection was associated with high levels of LDL-TG, HDL-TG, and small VLDL-TG, independent of other clinical factors. These findings indicate that active HCV G1b infection and advanced fibrosis are closely associated with abnormal serum TG profiles.
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Affiliation(s)
- Tomohisa Nagano
- Department of Gastroenterology and Hepatology Internal Medicine, Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan.
| | - Nobuyoshi Seki
- Department of Gastroenterology and Hepatology Internal Medicine, Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan.
| | - Yoichi Tomita
- Department of Gastroenterology and Hepatology Internal Medicine, Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan.
| | - Tomonori Sugita
- Department of Gastroenterology and Hepatology Internal Medicine, Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan.
| | - Yuta Aida
- Department of Gastroenterology and Hepatology Internal Medicine, Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan.
| | - Munenori Itagaki
- Department of Gastroenterology and Hepatology Internal Medicine, Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan.
| | - Satoshi Sutoh
- Department of Gastroenterology and Hepatology Internal Medicine, Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan.
| | - Hiroshi Abe
- Department of Gastroenterology and Hepatology Internal Medicine, Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan.
| | - Akihito Tsubota
- Core Research Facilities for Basic Science, Research Center for Medical Science, Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan.
| | - Yoshio Aizawa
- Department of Gastroenterology and Hepatology Internal Medicine, Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan.
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Van Thiel DH, George M, Attar BM, Ramadori G, Ion-Nedelcu N. Plasma triglyceride levels may modulate hepatitis C viral replication. Dig Dis Sci 2014; 59:881-5. [PMID: 24563239 DOI: 10.1007/s10620-014-3079-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2013] [Accepted: 02/11/2014] [Indexed: 12/21/2022]
Abstract
BACKGROUND Plasma and hepatic lipid abnormalities are frequent in hepatitis C infected individuals. METHODS Plasma lipid and medical records profiles were prospectively obtained in 130 consecutive individuals seen by a single hepatologist in a university liver disease clinic. The relationships between viral load, genotype, plasma lipid fractions, HDL, LDL particle number and particle size were examined. RESULTS Of 130 individuals studied, 74 had hepatitis C while 15 had NAFLD/NASH and 30 had alcohol related liver disease. The LDL particle number and LDL-C levels did not differ between those with and without hepatitis C although the number of small LDL particles was greater in those with hepatitis C infection. The HDL-C and total cholesterol levels were greater in those without hepatitis C than those with hepatitis C (P = 0.009). In contrast, the serum triglyceride level was greater in the hepatitis C viral group (P = 0.013). Importantly, the hepatitis C viral load regardless of the genotype correlated directly with the triglyceride and VLDL levels with r values of 0.73 and 0.84, respectively. CONCLUSIONS There are: (1) important differences in lipid classes, number and the size of lipid particles exist between hepatitis C virus infected and noninfected liver disease groups, (2) the serum total triglyceride and the LDL levels correlate significantly with the hepatitis C viral load and, (3) Serum triglyceride level may play an important role in viral replication. These data further suggest that therapies directed at lowering plasma triglyceride levels may enhance the efficacy of current antiviral treatment regimens.
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