scholarly journals Metabolic Disorders and Steatosis in Patients with Chronic Hepatitis C: Metabolic Strategies for Antiviral Treatments

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Munechika Enjoji ◽  
Motoyuki Kohjima ◽  
Kazuhiro Kotoh ◽  
Makoto Nakamuta
Keyword(s):  
Insulin Resistance ◽  
Chronic Hepatitis ◽  
Lipid Metabolism ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Metabolic Disorders ◽  
Current Knowledge ◽  
Antiviral Treatment ◽  
Treatment Options ◽  
Hcv Infection

It has been reported that hepatitis C virus (HCV) infection is closely associated with hepatic metabolic disorders. Hepatic steatosis and insulin resistance are both relatively common in patients with chronic hepatitis C. Recent investigations suggest that HCV infection changes the expression profile of lipid-metabolism-associated factors in the liver, conferring advantages to the life cycle of HCV. Moreover, insulin resistance and steatosis are independent predictors of impaired response to antiviral treatment in chronic hepatitis C. In this paper, we summarize our current knowledge of hepatic metabolic disorders and describe how HCV leads to and exploits these hepatic disorders. We also discuss the clinical significance of insulin sensitizers used to improve insulin resistance and lipid modulators used to manage lipid metabolism as potential treatment options for chronic hepatitis C.

Genetic polymorphisms as the predictors of response to antiviral treatment in chronic hepatitis C virus infection

2011 ◽  
Vol 152 (22) ◽  
pp. 876-881
Author(s):  
Alajos Pár
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Genetic Polymorphisms ◽  
Chronic Hepatitis C ◽  
Genome Wide Association Study ◽  
Antiviral Treatment ◽  
Hcv Infection ◽  
Snp Analysis ◽  
Chronic Hcv

The review discusses the genetic polymorphisms involved in the pathogenesis of hepatitis C virus (HCV) infection, that may determine the outcome of disease. In this field earlier both certain major histocompatibility complex (MHC) alleles and some cytokine gene variants have also been studied. Recently, the genome-wide association study (GWAS) and targeted single nucleotide polymorphism (SNP) analysis have revealed that a variant in the promoter region of interleukin-28B (IL-28B) gene is strongly linked to viral clearance and it may be the strongest pretreatment predictor of treatment response in chronic hepatitis C. Last year it was shown that two genetic variants leading to inosine triphosphatase deficiency protect against haemolytic anemia in patients receiving ribavirin during antiviral treatment for chronic HCV infection. Orv. Hetil., 2011, 152, 876–881.

scholarly journals Disorders of carbohydrate-lipid metabolism and galectin-3 level as factors of liver fibrosis progression in chronic hepatitis C

2021 ◽  
Vol 93 (2) ◽  
pp. 164-168
Author(s):  
V. A. Kovalevа ◽  
N. S. Zhevnerova ◽  
T. V. Antonova
Keyword(s):  
Insulin Resistance ◽  
Liver Cirrhosis ◽  
Chronic Hepatitis ◽  
Lipid Metabolism ◽  
Hepatitis C ◽  
Liver Fibrosis ◽  
Chronic Hepatitis C ◽  
Abdominal Obesity ◽  
The Body ◽  
Galectin 3

Aim. To assess the effect of metabolic disorders and galectin-3 levels on the progression of liver fibrosis in chronic hepatitis C. Materials and methods. 106 patients with HCV without decompensated liver cirrhosis were examined. Exclusion criteria: age younger than 20 and older than 65 years, diabetes, coronary heart disease, hypertension, alcoholism, drug addiction. Laboratory examination (biochemical blood test, enzyme immunoassay (ELISA) with determination of HCV-Ab antibodies, viral load) was supplemented with liver elastometry (Fibroscan) with fibrosis assessment (kPa, METAVIR scale). The body mass index of Quetelet (kg/m2), the presence of abdominal obesity, insulin resistance were evaluated. Serum levels of insulin and galectin-3 were determined by ELISA. Results. In 45% of patients, an increase in ITM was revealed, in 44% abdominal obesity, in 62% insulin resistance. In 75% abdominal obesity was determined in patients with liver fibrosis F3F4. Insulin resistance was found more often in patients with fibrosis F01 56.7%. Significant correlations between the level of galectin-3 and the degree of liver fibrosis (in kPa) [r=0,206, p=0,034], as well as the stage of liver fibrosis (on the METAVIR scale) [r=0,247, p=0,01] were obtained. The level of galectin-3 in liver cirrhosis was 6.32 (4.57; 9.64) ng/ml, which is significantly higher than in F0 3.96 (1.45; 5.30) ng/ml (p=0.002) and F1 3.85 (2.20; 5.83) ng/ml (p=0.002). By calculating the specificity and sensitivity of isolated for F4 stage of liver fibrosis (ROC-curve, the level of galectin-3 is 5.21 ng/ml), the level of specificity of 74.7%, sensitivity of 74% was established. Conclusion. We found a significant relationship between the disturbances of carbohydrate-lipid metabolism and liver fibrosis, the level of galectin-3 and fibrosis stage of the liver. The prognostic value of increasing the level of galectin-3 for predicting the cirrhotic stage of liver fibrosis is substantiated.

scholarly journals Hepatitis C Virus Infection Induces Hepatic Expression of NF-κB-Inducing Kinase and Lipogenesis by Downregulating miR-122

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Brianna Lowey ◽  
Laura Hertz ◽  
Stephan Chiu ◽  
Kristin Valdez ◽  
Qisheng Li ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Lipid Metabolism ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Human Hepatocytes ◽  
Hcv Infection ◽  
Pivotal Role ◽  
Cellular Lipid

ABSTRACT Hepatitis C virus (HCV) harnesses host dependencies to infect human hepatocytes. We previously identified a pivotal role of IκB kinase α (IKK-α) in regulating cellular lipogenesis and HCV assembly. In this study, we defined and characterized NF-κB-inducing kinase (NIK) as an IKK-α upstream serine/threonine kinase in IKK-α-mediated proviral effects and the mechanism whereby HCV exploits this innate pathway to its advantage. We manipulated NIK expression in Huh7.5.1 cells through loss- and gain-of-function approaches and examined the effects on IKK-α activation, cellular lipid metabolism, and viral assembly. We demonstrated that NIK interacts with IKK-α to form a kinase complex in association with the stress granules, in which IKK-α is phosphorylated upon HCV infection. Depletion of NIK significantly diminished cytosolic lipid droplet content and impaired HCV particle production. NIK overexpression enhanced HCV assembly, and this process was abrogated in cells deprived of IKK-α, suggesting that NIK acts upstream of IKK-α. NIK abundance was increased in HCV-infected hepatocytes, liver tissues from Alb-uPA/Scid mice engrafted with human hepatocytes, and chronic hepatitis C patients. NIK mRNA contains an miR-122 seed sequence binding site in the 3′ untranslated region (UTR). miR-122 mimic and hairpin inhibitor directly affected NIK levels. In our hepatic models, miR-122 levels were significantly reduced by HCV infection. We demonstrated that HNF4A, a known transcriptional regulator of pri-miR-122, was downregulated by HCV infection. NIK represents a bona fide target of miR-122 whose transcription is downregulated by HCV through reduced HNF4A expression. This effect, together with the sequestering of miR-122 by HCV replication, results in “derepression” of NIK expression to deregulate lipid metabolism. IMPORTANCE Chronic hepatitis C virus (HCV) infection is a major global public health problem. Infection often leads to severe liver injury that may progress to cirrhosis, hepatocellular carcinoma, and death. HCV coopts cellular machineries for propagation and triggers pathological processes in the liver. We previously identified a pivotal role of IKK-α in regulating cellular lipid metabolism and HCV assembly. In this study, we characterized NIK as acting upstream of IKK-α and characterized how HCV exploits this innate pathway to its advantage. Through extensive mechanistic studies, we demonstrated that NIK is a direct target of miR-122, which is regulated at the transcription level by HNF4A, a hepatocyte-specific transcription factor. We show in HCV infection that NIK expression is increased while both HNF4A and miR-122 levels are decreased. NIK represents an important host dependency that links HCV assembly, hepatic lipogenesis, and miRNA biology.

scholarly journals HOMA, BMI, and Serum Leptin Levels Variations during Antiviral Treatment Suggest Virus-Related Insulin Resistance in Noncirrhotic, Nonobese, and Nondiabetic Chronic Hepatitis C Genotype 1 Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Alessandro Grasso ◽  
Federica Malfatti ◽  
Gabriella Andraghetti ◽  
Simona Marenco ◽  
Chiara Mazzucchelli ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Chronic Hepatitis ◽  
Viral Load ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Antiviral Treatment ◽  
Genotype 1 ◽  
Serum Leptin ◽  
Peginterferon And Ribavirin ◽  
Chronic Hcv

Objective. To investigate the relationship between insulin resistance and viral load decay in nondiabetic and noncirrhotic genotype 1 chronic HCV patients during peginterferon and ribavirin treatment and the possible influence of BMI and leptin as metabolic confounders.Methods. 75 consecutive noncirrhotic, nonobese, and nondiabetic patients with genotype 1 chronic hepatitis C treated with peginterferon alpha 2a plus ribavirin were evaluated. HOMA-IR, serum leptin, and BMI were measured in all patients at baseline and at weeks 12 and 48, whereas viral load was measured at the same time points and then 24 weeks after the end of treatment.Results. HOMA-IR was significantly associated with both BMI and leptin at baseline. During peginterferon plus ribavirin treatment, there was a significant reduction of HOMA-IR at weeks 12 and 48 from baseline (P=0.033and 0.048, resp.) in patients who achieved an early viral load decay (EVR), a trend not observed in patients who not achieved EVR. No variations during treatment were observed regarding BMI and leptin irrespective of EVR.Conclusion. The early reduction of HOMA-IR but not of BMI and leptin during antiviral treatment in noncirrhotic, chronic hepatitis C genotype 1 patients who achieved EVR suggests a viral genesis of insulin resistance in patients with nonmetabolic phenotype.

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