Immune responses and immunity in hepatitis C virus infection

Mizukoshi, Eishiro; Rehermann, Barbara

doi:10.1007/s005350170001

Cited by 22 publications

(22 citation statements)

References 93 publications

(92 reference statements)

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“…27,28 In general, Th1 cells produce cytokines such as interferon-gamma and tumor necrosis factor that promote inflammation and cellmediated immunity in an attempt to control infection. Th2 lymphocytes produce cytokines, especially interleukin 4 (IL-4), that favor fibrogenesis in liver injury to a greater extent than Th1 lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Intrahepatic gene expression profiles and alpha‐smooth muscle actin patterns in hepatitis C virus induced fibrosis†

et al. 2005

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To gain insight into pathogenic mechanisms underlying fibrosis in hepatitis C virus (HCV)-mediated liver injury, we compared intrahepatic gene expression profiles in HCV-infected patients at different stages of fibrosis and ␣-smooth muscle actin (␣-SMA) staining patterns. We studied 21 liver biopsy specimens: 5 had no fibrosis (Ludwig-Batts stage 0); 10 had early portal or periportal fibrosis (stages 1 and 2); and 6, advanced fibrosis (stages 3 and 4). None of the patients had hepatocellular carcinoma. Transcriptional profiles were determined by high-density oligonucleotide microarrays. ANOVA identified 157 genes for which transcript abundance was associated with fibrosis stage. These defined three distinct hierarchical clusters of patients. Patients with predominantly stage 0 fibrosis had increased abundance of mRNAs linked to glycolipid metabolism. PDGF, a potent stellate cell mitogen, was also increased. Transcripts with increased abundance in stages 1 and 2 fibrosis were associated with oxidative stress, apoptosis, inflammation, proliferation, and matrix degradation, whereas transcripts increased in stages 3 and 4 were associated with fibrogenesis and cellular proliferation. Cells staining for ␣-SMA were detectable at all stages but infrequent in advanced fibrosis without active inflammation. A high frequency of such cells was associated with mRNAs linked to glycolipid metabolism. In conclusion, the presence of ␣-SMA-

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Section: Discussionmentioning

confidence: 99%

Intrahepatic gene expression profiles and alpha‐smooth muscle actin patterns in hepatitis C virus induced fibrosis†

et al. 2005

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“…12 This concept is supported by the observation that individuals with chronic infection are often found to have relatively weak and narrowly directed CD4 + and CD8 + T cell responses against HCV. 13,14 Interestingly, recent data have demonstrated that although chronically infected individuals can have a greater number of circulating HCV specific CD8 + T cells than those who have cleared the virus, these T cells are functionally impaired and may potentially contribute to the lack of viral clearance. 15 This failure of the host immune response to eliminate HCV may be due in part to the rapid generation of viral variants during the course of infection 16 and weak immunogenicity resulting from low level viral replication.…”

Section: Introductionmentioning

confidence: 99%

Priming of CD4+ and CD8+ T cell responses using a HCV core ISCOMATRIX™ vaccine: A phase I study in healthy volunteers

Drane¹,

Maraskovsky²,

Gibson³

et al. 2009

Human Vaccines

101

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“…[22][23][24] Further, TNF␣ and IL6 are proinflammatory molecules released during liver cell injury, the principal consequence of chronic viral hepatitis. 25,26 To date, the role of these cytokines in HCVinduced IR remains controversial. Further, there is no consensus in the literature on whether alterations in these adipocytokines contribute to liver cell injury and inflammation in chronic HCV infection.…”

mentioning

confidence: 99%

Insulin resistance and liver injury in hepatitis C is not associated with virus-specific changes in adipocytokines

et al. 2007

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The role of tumor necrosis factor ␣, interleukin 6, leptin, and adiponectin in the pathogenesis of hepatitis C virus (HCV)-associated insulin resistance (IR) remains controversial. We tested the hypothesis that these adipocytokines contribute to chronic HCV-associated IR and liver injury by first comparing their serum levels and homeostasis model assessment of insulin resistance (HOMA-IR) in 154 untreated, non-diabetic, HCV-infected male subjects with fibrosis stage 0-2, to that in 75 healthy volunteers matched for age, body mass index (BMI), and waist-hip ratio (WHR). We next examined whether the adipocytokine levels were associated with the extent of hepatic steatosis, portal/periportal inflammation and fibrosis in our total cohort of 240 HCVinfected male subjects. Significantly higher levels of HOMA-IR (2.12 versus 1.63, P ‫؍‬ 0.01), TNF␣ (1.28 versus 0.60 pg/ml, P < 0.001) and IL6 (2.42 versus 1.15 pg/ml, P ‫؍‬ 0.001) were noted in the HCV cohort compared with healthy controls respectively, but there were no significant differences in leptin and adiponectin concentrations. C hronic hepatitis C virus (HCV) infection is associated with the development of hepatic steatosis 1-5 and unique, virus-specific alterations in host metabolism leading to the development of insulin resistance (IR) and type 2 diabetes mellitus (T2DM). [6][7][8][9] We and others have shown that chronic HCV infection is associated with the development of IR in the absence of overt T2DM, irrespective of the presence or absence of cirrhosis. 6,10 Further, IR as assessed by the homeostasis model (HOMA-IR) 11 was independently associated with virally-mediated portal inflammation and an increased rate of fibrosis progression, indicating that IR is a cause rather than a consequence of hepatic fibrosis in HCV infection. 6 Despite recent recognition of the important role of IR in the progression of liver injury in HCV infection [12][13][14] and the response to antiviral therapy, 12,14,15 the mechanism of HCV-induced IR is not known. There is an abundance of literature to suggest that adipose tissue-derived cytokines (adipocytokines) may play a key role in the development of obesity-related IR. 16,17 TNF␣, IL6 and leptin are proinflammatory cytokines that can directly alter glucose and lipid metabolism. [16][17][18] In contrast, adiponectin, the most abundant of all the adipocytokines has an opposite effect, increasing insulin sensitivity [16][17][18] and having anti-steatotic, 19 anti-inflammatory 20 and antifibrotic effects. 21 In nonalcoholic fatty liver disease, it has been shown that serum levels of the various adipocyto-

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Immune responses and immunity in hepatitis C virus infection

Cited by 22 publications

References 93 publications

Intrahepatic gene expression profiles and alpha‐smooth muscle actin patterns in hepatitis C virus induced fibrosis†

Intrahepatic gene expression profiles and alpha‐smooth muscle actin patterns in hepatitis C virus induced fibrosis†

Priming of CD4+ and CD8+ T cell responses using a HCV core ISCOMATRIX™ vaccine: A phase I study in healthy volunteers

Insulin resistance and liver injury in hepatitis C is not associated with virus-specific changes in adipocytokines

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