Viral hepatitis and liver cancer: the case of hepatitis C

Levrero, Massimo

doi:10.1038/sj.onc.1209562

Cited by 369 publications

(277 citation statements)

References 193 publications

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“…Much like smoking, chronic hepatitis C (HCV) infection has also been shown to lead to significant increases in cellular stress signals, such as DNA damage and inflammation signaling, and is strongly associated with the development of hepatocellular carcinoma (Levrero, 2006). In a recent study, evidence was provided that the MDM2 SNP309 locus alters the risk of developing liver cancer associated with chronic HCV infection (Dharel et al, 2006).…”

Section: Stresses Such As Smoking and Chronic Hcv Infectionmentioning

confidence: 99%

A single nucleotide polymorphism in the p53 pathway interacts with gender, environmental stresses and tumor genetics to influence cancer in humans

2007

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Cancer biology finds itself in a post-genomic era and the hopes of using inherited genetic variants to improve prevention and treatment strategies are widespread. One of the largest types of inherited genetic variation is the single nucleotide polymorphism (SNP), of which there are at least 4.5 million. The challenge now becomes how to discover which polymorphisms alter cancer in humans and how to begin to understand their mechanism of action. In this report, a series of recent publications will be reviewed that have studied a polymorphism in the p53 tumor suppressor pathway, MDM2 SNP309. These reports have lent insights into how germline genetic variants of the p53 pathway could interact with gender, environmental stresses and tumor genetics to affect cancer in humans. Importantly, these observations have also exposed potential nodes of intervention, which could prove valuable in both the prevention and treatment of this disease in humans.

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Section: Stresses Such As Smoking and Chronic Hcv Infectionmentioning

confidence: 99%

A single nucleotide polymorphism in the p53 pathway interacts with gender, environmental stresses and tumor genetics to influence cancer in humans

2007

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“…(HEPATOLOGY 2012;56:39-48) H epatitis C virus (HCV) is a member of the Flaviviridae family and a major cause of chronic hepatitis often leading to liver cirrhosis and hepatocellular carcinoma. 1 Chronic hepatitis C is a complex disease associated with host metabolic modifications resulting in a unique metabolic syndrome including insulin resistance, liver steatosis, and hypobetalipoproteinemia. 2,3 The most striking link between HCV and lipids resides in the association of HCV particles with lipoproteins.…”

mentioning

confidence: 99%

High plasma level of nucleocapsid-free envelope glycoprotein-positive lipoproteins in hepatitis C patients

et al. 2012

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Hepatitis C virus (HCV) particles associate viral and lipoprotein moieties to form hybrid lipoviral particles (LVPs). Cell culture-produced HCV (HCVcc) and ex vivo-characterized LVPs primarily differ by their apolipoprotein (apo) B content, which is low for HCVcc, but high for LVPs. Recombinant nucleocapsid-free subviral LVPs are assembled and secreted by apoB-producing cell lines. To determine whether such subviral particles circulate in HCV-infected individuals, LVPs complexed with immunoglobulin were precipitated with protein A from low-density plasma fractions of 36 hepatitis C patients, and their lipid content, apolipoprotein profile, and viral composition were determined. HCV RNA in LVPs was quantified and molar ratios of apoB and HCV genome copy number were calculated. LVPs lipidome from four patients was determined via electrospray ionization/tandem mass spectrometry. Protein A-purified LVPs contained at least the envelope glycoprotein E2 and E2-specific antibodies. LVPs were present in every patient and were characterized by high lipid content, presence of apolipoproteins characteristic of triglyceride-rich lipoproteins (TRLs), HCV RNA, and viral glycoprotein. Importantly, save for four patients, LVPs fractions contained large amounts of apoB, with on average more than 1 3 10 6 apoB molecules per HCV RNA genome. Because there is one apoB molecule per TRL, this ratio suggested that most LVPs are nucleocapsid-free, envelope glycoprotein-containing subviral particles. LVPs and TRLs had similar composition of triacylglycerol and phospholipid classes. Conclusion: LVPs are a mixed population of particles, comprising predominantly subviral particles that represent a distinct class of modified lipoproteins within the TRL family. (HEPATOLOGY 2012;56:39-48) H epatitis C virus (HCV) is a member of the Flaviviridae family and a major cause of chronic hepatitis often leading to liver cirrhosis and hepatocellular carcinoma. 1 Chronic hepatitis C is a complex disease associated with host metabolic modifications resulting in a unique metabolic syndrome including insulin resistance, liver steatosis, and hypobetalipoproteinemia. 2,3 The most striking link between HCV and lipids resides in the association of HCV particles with lipoproteins. 4,5 Indeed, HCV virions with a density <1.06 g/mL are associated with lipoproteins, thus forming hybrid particles known as lipoviral particles (LVPs). These low-density viral particles are globular, rich in triacylglycerol and total cholesterol (TChol) and contain the viral envelope glycoproteins and nucleocapsid (composed of HCV RNA and core protein). In addition, LVPs contain all the apolipoproteins (apo) that define the triacylglycerolrich lipoproteins (TRLs). Indeed, apolipoprotein (apo) B, apoE, apoCI, apoCII, and apoCIII, all of which characterize very low-density, intermediate-density, and low-density lipoproteins (VLDL, IDL, and LDL,

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“…2,3 On the other hand, HCV constituents also stimulate inflammatory pathways, e.g., via triggering of toll-like receptors (TLRs).…”

mentioning

confidence: 99%

The toll‐like receptor 2 (TLR2) ‐196 to ‐174 del/ins polymorphism affects viral loads and susceptibility to hepatocellular carcinoma in chronic hepatitis C

Nischalke

Coenen

Berger

et al. 2011

Intl Journal of Cancer

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Chronic hepatitis C virus (HCV) infection is a major risk factor for hepatocellular carcinoma (HCC). HCV proteins core and NS3 can bind to toll-like receptor 2 (TLR2) and trigger inflammatory responses. Polymorphisms in the TLR2 gene predispose to various forms of malignancy but have not been studied in HCV-associated HCC. Here, we investigated whether single nucleotide polymorphisms (SNPs), rs4696480, rs5743708, rs5743704 and the -196 to -174 del/ins polymorphism of the TLR2 gene affect the risk for HCC in chronic hepatitis C. The study involved 189 and 192 HCV genotype 1 infected patients with and without HCC, respectively, as well as 347 healthy controls. TLR2 alleles were determined by hybridization probe assays and allele-specific short fragment polymerase chain reaction on a LightCycler system. All TLR2 polymorphisms matched the HardyWeinberg equilibrium in each study group. Although TLR2 SNPs showed no effect, the frequency of the TLR2 -196 to -174 del allele was significantly higher in patients with HCV-associated HCC (22.5%) than in HCV-infected patients without HCC (15.6%, p 5 0.016) and healthy controls (15.3%, p 5 0.003). HCV-infected carriers of a TLR2 -196 to -174 del allele had significantly higher HCV viral loads than TLR2 -196 to -174 ins/ins homozygous patients (p 5 0.031). Finally, in carriers of the TLR2 -196 to -174 del allele, stimulation of monocytes resulted in significantly lower TLR2 expression levels and interleukin-8 (IL-8) induction than in individuals with the TLR2 -196 to -174 ins/ins genotype (p < 0.05). Our data suggest the TLR2 -196 to -174 del allele to affect HCV viral loads and to increase the risk for HCC in HCV genotype1-infected patients.

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Viral hepatitis and liver cancer: the case of hepatitis C

Cited by 369 publications

References 193 publications

A single nucleotide polymorphism in the p53 pathway interacts with gender, environmental stresses and tumor genetics to influence cancer in humans

A single nucleotide polymorphism in the p53 pathway interacts with gender, environmental stresses and tumor genetics to influence cancer in humans

High plasma level of nucleocapsid-free envelope glycoprotein-positive lipoproteins in hepatitis C patients

The toll‐like receptor 2 (TLR2) ‐196 to ‐174 del/ins polymorphism affects viral loads and susceptibility to hepatocellular carcinoma in chronic hepatitis C

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