Myxovirus resistance, osteopontin and suppressor of cytokine signaling 3 polymorphisms predict hepatitis C virus therapy response in an admixed patient population: comparison with IL28B

Angelo, Ana Luiza Dias; Cavalcante, Lourianne Nascimento; Abe‐Sandes, Kiyoko; Machado, Taisa Bonfim; Lemaire, Denise Carneiro; Malta, Fernanda de Mello; Pinho, João Renato Rebello; Lyra, Luiz Guilherme Costa; Lyra, André Castro

doi:10.6061/clinics/2013(10)06

Cited by 7 publications

(10 citation statements)

References 29 publications

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“…Two SNPs in SPP1, the gene encoding osteopontin, a protein exerting cytokine-like functions that are important for efficient Th-1 immune responses, were consistently associated with increased (ins155G) and decreased (rs11730582) sustained viral response (SVR) rates after treatment with IFN-based treatments [59][60][61]. Another SNP (rs17000900) located within MX1, a gene belonging to the group of ISGs, was associated with increased SVR rates [60,62], although this association was not observed by others [59]. There is a clear need for well conducted systematic reviews and metaanalyses to reconcile the results from candidate genes studies.…”

Section: Genetic Associations With Spontaneous and Treatment-induced mentioning

confidence: 99%

Host – hepatitis C viral interactions: The role of genetics

Heim

Bochud

George

2016

Journal of Hepatology

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Hepatitis C virus (HCV) is a major cause of chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma. Only a minority of patients can clear the virus spontaneously. Elimination of HCV during acute infection correlates with a rapid induction of innate, especially interferon (IFN)-induced genes, and a delayed induction of adaptive immune responses. There is a strong association between genetic variants in the IFNλ (IL28B) locus with the rate of spontaneous clearance. Individuals with the ancestral IFNλ4 allele capable of producing a fully active IFNλ4 are paradoxically not able to clear HCV in the acute phase and develop chronic hepatitis C (CHC) with more than 90% probability. In the chronic phase of HCV infection, the wild-type IFNλ4 genotype is strongly associated with an induction of hundreds of classical type I/type III IFN stimulated genes in hepatocytes. However, the activation of the endogenous IFN system in the liver is ineffective in clearing HCV, and is even associated with impaired therapeutic responses to pegylated (Peg)IFNα containing treatments. While the role of genetic variation in the IFNλ locus to the outcome of CHC treatment has declined, it is clear that variation not only at this locus, but also at other loci, modulate clinically important liver phenotypes, including inflammation, fibrosis progression and the development of hepatocellular cancer. In this review, we summarize current knowledge about the role of genetics in the host response to viral hepatitis and the potential future evolution of knowledge in understanding host-viral interactions.

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Section: Genetic Associations With Spontaneous and Treatment-induced mentioning

confidence: 99%

Host – hepatitis C viral interactions: The role of genetics

Heim

Bochud

George

2016

Journal of Hepatology

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“…Polymorphisms of some other genes coding for the proteins which have a role in the immune response have also been shown to correlate with spontaneous/therapy-induced virus clearance. One of these genes is the gene for osteopontin which initiates T helper cells type 1 response, and has been shown to associate with the sustained viral response after the IFN therapy [35,36]. Today, the role of the host genetic variability has been reduced due to high efficacy of new era interferon-free antiviral therapy.…”

Section: Hcv Infection Induces Production Of Interferons λ (Ifn-λ) Imentioning

confidence: 99%

Hepatitis C: Host and Viral Factors Associated with Response to Therapy and Progression of Liver Fibrosis

Jovanović-Ćupić¹,

Božović²,

Krajnović³

et al. 2018

Hepatitis C - From Infection to Cure

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The goal of this study was to identify the baseline host and viral factors of response to antiviral therapy in patients with chronic hepatitis C. Compared with interferon/ribavirin therapy, new current direct-acting antiviral (DAA) combination regimens significantly increased rate of sustained virologic response (SVR) and shorter treatment durations, but is still limited by viral resistance, adverse effects, and high cost especially in developing countries. Human genetic factors and heterogeneity within the HCV genome may be associated with virologic treatment failure before and after antiviral therapy. Further, HCV infection may contribute to the development of HCV-related liver disease and hepatocarcinogenesis, through modulating genetic and epigenetic state of certain genes implicated in control of critical cellular pathways. Previous results confirm the importance of host and viral factors and virus-induced genetic and epigenetic changes in predicting outcome and treatment response.

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“…Specific studies have investigated factors related to INF treatment resistance (Afzal et al, 2011;Pawlotsky, 2003;Zhou et al, 2011). While the resistance to DAA's treatment is caused by the described amino acid alterations related to the interaction sites between drugs and viral proteins (Alves et al, 2013;Cento et al, 2012;Lin et al, 2004), the resistance to the INF plus RBV therapy seems to be a multifactorial process that includes baseline viral population, host genotype of IL28B, immune factors, presence or absence of comorbidities as renal disease and coinfection (Angelo et al, 2013;Del Campo et al, 2013;Toyoda et al, 2011). Using techniques that are suitable to detect minor viral variants, we demonstrated previously that lower genetic diversity represents higher rates of sustained virological response.…”

Section: Introductionmentioning

confidence: 99%

Evidence of bottleneck effect on hepatitis C virus transmission between a couple under interferon based therapy

Silva

Carvalho-Mello

Matos

et al. 2017

Infection, Genetics and Evolution

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Issues on the correlation of viral genetic diversity and treatment response to the hepatitis C infection remain uncertain. The bottleneck effect dictates the characteristics of the viral population that will establish the infection in a new host and is related to how the immune system and treatment will be effective against the virus. Here we evaluated the phylogenetic characteristics of quasispecies population and the treatment response pattern of a HCV infected couple. We also analyzed whether the viral population of these patients indicated that they were exposed to the same source for primer infection. This study included two patients (P10 and P11) HCV genotype 1b infected. The couple presented horizontal transmission. Viral RNA was isolated from serum samples collected before, during and after treatment, at specific time points. The HCV NS5A gene sequence was amplified, cloned and sequenced. Genetic and evolutionary analyses were performed to compare the quasispecies population of these two patients and local control patients. Genetic distance and diversity were calculated. Phylogenetic analyses were performed by using maximum likelihood and Bayesian methodologies. The analysis of the baseline samples showed that the genetic distance of the viral populations of patients P10 and P11 was significantly lower than when these patients and the control group based on sequences from local patients were analyzed, supporting the horizontal transmission hypothesis. Phylogenetic analysis with sequences from all the time point samples also demonstrated two patterns of evolution depending on the treatment response. The Bayesian analysis showed that one isolate corresponding to the baseline sample of P10 was grouped into the P11 clade, suggesting a way of infection and a bottleneck effect. Our data suggests that the patient P11 viral population may be originated from variants from P10 patient and consequently showing that clinical differences between treatment responses can emerge from the bottleneck effect on viral populations.

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Myxovirus resistance, osteopontin and suppressor of cytokine signaling 3 polymorphisms predict hepatitis C virus therapy response in an admixed patient population: comparison with IL28B

Cited by 7 publications

References 29 publications

Host – hepatitis C viral interactions: The role of genetics

Host – hepatitis C viral interactions: The role of genetics

Hepatitis C: Host and Viral Factors Associated with Response to Therapy and Progression of Liver Fibrosis

Evidence of bottleneck effect on hepatitis C virus transmission between a couple under interferon based therapy

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