Serum lipids and chronic hepatitis C genotype 4: interaction and significance

Khattab, Mahmoud A.; Eslam, Mohammed; Aly, Mayada M.; Shatat, Mohammed; Mousa, Yousef; Abd-Aalhalim, Hesham; Aly, Hanan F.; Shaker, Yehia

doi:10.1016/s1665-2681(19)31484-x

Cited by 12 publications

(12 citation statements)

References 32 publications

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“…Although our analyses do not allow for a mechanistic explanation, they are consistent with previous reports from population-based studies and experimental models indicating that HCV RNA levels correlate positively, while HBV DNA levels correlate inversely, with serum TG. (21)(22)(23) From a teleological standpoint, the question remains how the E167K substitution in TM6SF2 rs58542926 might favor HBV replication and inhibit HCV. Previous studies have shown that blocking VLDL secretion by inhibiting MTTP with naringenin reduces the export of HCV, (39) while overexpression of seipin, a protein implicated in the maturation and fusion of lipid droplets in hepatoma cells subsequently infected with HCV, causes a significant decrease in virion export accompanied by the appearance of large lipid droplets (experimental steatosis).…”

Section: Discussionmentioning

confidence: 99%

“…A third unexplored but plausible consequence of TM6SF2 action is influences on viral load in chronic viral hepatitis. Both CHC and CHB are associated with abnormalities in lipid metabolism, (21)(22)(23) lipids play important roles in various aspects of the life cycle of the viruses, (24,25) and we have shown that a variable fraction of hepatitis C virus (HCV) in serum is associated with triglyceride-rich lipoproteins called lipoviral particles that exhibit increased infectivity. (26) Thus, it could be hypothesized that gene variants that modulate hepatic lipid metabolism and TG export could impact on viral load.…”

Section: International Liver Disease Genetics Consortiummentioning

confidence: 99%

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Diverse impacts of the rs58542926 E167K variant in TM6SF2 on viral and metabolic liver disease phenotypes

et al. 2016

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A genome-wide exome association study has identified the transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 variant encoding an E167K substitution as a genetic determinant of hepatic steatosis in nonalcoholic fatty liver disease (NAFLD). The roles of this variant across a spectrum of liver diseases and pathologies and on serum lipids comparing viral hepatitis to NAFLD and viral load in chronic viral hepatitis, as well as its intrahepatic molecular signature, have not been well characterized. We undertook detailed analyses in 3260 subjects with viral and nonviral liver diseases and in healthy controls. Serum inflammatory markers and hepatic expression of TM6SF2 and genes regulating lipid metabolism were assessed in a subset with chronic hepatitis C (CHC). The rs58542926 T allele was more prevalent in 502 NAFLD patients than controls (P 5 0.02) but not different in cohorts with CHC (n 5 2023) and chronic hepatitis B (n 5 507). The T allele was associated with alterations in serum lipids and hepatic steatosis in all diseases and with reduced hepatic TM6SF2 and microsomal triglyceride transfer protein expression. Interestingly, the substitution was associated with reduced CHC viral load but increased hepatitis B virus DNA. The rs58542926 T allele had no effect on inflammation, impacted F2 fibrosis in CHC and NAFLD assessed cross-sectionally (odds ratio 5 1.39, 95% confidence interval 1.04-1.87, and odds ratio 5 1.62, 95% confidence interval 1.03-2.52, respectively; P < 0.03 for both), but had no effect on fibrosis progression in 1174 patients with CHC and a known duration of infection. Conclusion: The TM6SF2 E167K substitution promotes steatosis and lipid abnormalities in part by altering TM6SF2 and microsomal triglyceride transfer protein expression and differentially impacts CHC and chronic hepatitis B viral load, while effects on fibrosis are marginal. (HEPATOLOGY 2016;64:34-46)

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Section: Discussionmentioning

confidence: 99%

Section: International Liver Disease Genetics Consortiummentioning

confidence: 99%

Diverse impacts of the rs58542926 E167K variant in TM6SF2 on viral and metabolic liver disease phenotypes

et al. 2016

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“…There is no consensus on TG levels in chronic HCV infection. Some studies have reported that TG levels were similar between patients with active HCV and control groups [ 17 , 18 , 19 ], while others reported a decreased level of TG during active HCV infection [ 20 , 21 ]. Significant differences were noted in the distribution of TG in lipoprotein fractions.…”

Section: Discussionmentioning

confidence: 99%

Impact of Chronic Hepatitis C Virus Genotype 1b Infection on Triglyceride Concentration in Serum Lipoprotein Fractions

Nagano

Seki

Tomita

et al. 2015

IJMS

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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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“…Altered serum lipid profiles are common histologic features of chronic infection with HCV [ 15 ]. Chronic HCV patients exhibit low levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) compared with uninfected controls [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Hepatitis C Virus Increases Free Fatty Acids Absorption and Promotes its Replication Via Down-Regulating GADD45α Expression

Chen

et al. 2016

Med Sci Monit

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BackgroundHepatitis C virus (HCV) infection, as a major cause of chronic hepatic diseases, is always accompanied with an abnormality of lipid metabolism. The aim of this study was to investigate the pathogenic role of free fatty acids (FFA) in human HCV infection.Material/MethodsPeripheral blood lipid indexes among HCV patients with different viral loads (199 samples) and healthy donors (80 samples) were detected by clinical biochemistry tests. HCV replication and the expression of growth arrest and DNA-damage-inducible gene 45-α (GADD45α) in Huh7 cells and clinical samples were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Lipid accumulation in Huh7 cells was detected by immunofluorescence.ResultsIn this study, we found that FFA showed a significant positive correlation with viral load in peripheral blood of HCV patients, but not total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C). GADD45α expression in HCV patients dramatically decreased with the increase of viral load. In Huh7 cells, FFA treatment significantly enhanced HCV replication. HCV infection inhibited GADD45α expression, and this effect was further enhanced with the presence of FFA treatment. Ectopic expression of GADD45α in HCV-infected Huh7 cells markedly inhibited the absorption of FFA and HCV replication. However, FFA significantly elevated GADD45α expression without HCV infection.ConclusionsThese results demonstrated that HCV down-regulates GADD45α expression to enhance FFA absorption and thus facilitate its replication. GADD45α is an essential mediator for the pathogenesis of HCV infection. Thus, our study provides potential clues in the search for novel therapeutics and fatty lipid control options for HCV patients.

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Serum lipids and chronic hepatitis C genotype 4: interaction and significance

Cited by 12 publications

References 32 publications

Diverse impacts of the rs58542926 E167K variant in TM6SF2 on viral and metabolic liver disease phenotypes

Diverse impacts of the rs58542926 E167K variant in TM6SF2 on viral and metabolic liver disease phenotypes

Impact of Chronic Hepatitis C Virus Genotype 1b Infection on Triglyceride Concentration in Serum Lipoprotein Fractions

Hepatitis C Virus Increases Free Fatty Acids Absorption and Promotes its Replication Via Down-Regulating GADD45α Expression

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