Natural killer cell receptor and HLA-C gene polymorphisms among patients with hepatitis C: a comparison between sustained virological responders and non-responders

Carneiro, Valdirene Leão; Lemaire, Denise Carneiro; Bendicho, Maria Teresita; Souza, Sabrina L.; Cavalcante, Lourianne Nascimento; Angelo, Ana Luiza Dias; Freire, Songelí Menezes; Mendes, Carlos Maurício Cardeal; Santana, Nelma; Lyra, Luiz Guilherme Costa; Lyra, André Castro

doi:10.1111/j.1478-3231.2010.02212.x

Cited by 24 publications

(21 citation statements)

References 26 publications

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“…Further, subgroup analyses showed that the best outcomes were achieved in studies in which patients were either predominantly HIV-negative (HIV−), predominantly infected with an HCV genotype other than 1 or 4, or treated with ribavirin. The proportion of patients who achieved an SVR in the 20 studies that included patients with all three of these characteristics ranged from 45% (95% CI: 34-55) 70 to 78% (95% CI: 61-91) 71 and the pooled proportion was 65% (95% CI: [61][62][63][64][65][66][67][68]. The presence of the interleukin-28B polymorphism was associated with a high SVR rate in the two studies which reported relevant data.…”

Section: Study Outcomesmentioning

confidence: 99%

Chronic hepatitis C treatment outcomes in low- and middle-income countries: a systematic review and meta-analysis

Ford

Kirby

Singh

et al. 2012

Bull. World Health Organ.

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Section: Study Outcomesmentioning

confidence: 99%

Chronic hepatitis C treatment outcomes in low- and middle-income countries: a systematic review and meta-analysis

Ford

Kirby

Singh

et al. 2012

Bull. World Health Organ.

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“…Classical and nonclassical MHC molecules serve as ligands for these NK receptors. It is noteworthy that inheritance of particular KIR genes or their polymorphisms involved in the control of NK activity predispose to chronic infection or treatment resistance (19)(20)(21)(22)(23). Expression levels of these inhibitory and stimulatory receptors on NK cells and their ligands on hepatocytes, cholangiocytes, stellate cells, and Kupffer cells are significantly altered during HCV infection and contribute to the pathogenesis and progression of liver disease (24,25).…”

Section: H Epatitis C Virus (Hcv) Infection Is a Global Health Problementioning

confidence: 99%

KLRG1 Negatively Regulates Natural Killer Cell Functions through the Akt Pathway in Individuals with Chronic Hepatitis C Virus Infection

Wang

Cheng

Shi

et al. 2013

J Virol

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In this study, we demonstrate that killer cell lectin-like receptor subfamily G member 1 (KLRG1), a transmembrane protein preferentially expressed on T cells, is highly expressed on CD56 ؉ NK cells, which are significantly reduced in their numbers and functions in the peripheral blood of patients with chronic hepatitis C virus (HCV) infection compared to subjects without infection. KLRG1 expression is also upregulated on healthy NK cells exposed to Huh-7 hepatocytes infected with HCV in vitro. Importantly, the expression levels of KLRG1 are inversely associated with the capacity of NK cells to proliferate and to produce gamma interferon (IFN-␥) but positively associated with apoptosis of NK cells in response to inflammatory cytokine stimulation. KLRG1؉ NK cells, including CD56 bright and CD56 dim subsets, exhibit impaired cell activation and IFN-␥ production but increased apoptosis compared to KLRG1؊ NK cells, particularly in HCV-infected individuals. Importantly, blockade of KLRG1 signaling significantly recovered the impaired IFN-␥ production by NK cells from HCV-infected subjects. Blockade of KLRG1 also enhanced the impaired phosphorylation of Akt (Ser473) in NK cells from HCV-infected subjects. Taken together, these results indicate that KLRG1 negatively regulates NK cell numbers and functions via the Akt pathway, thus providing a novel marker and therapeutic target for HCV infection.

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“…SVR rates in individual studies in Brasil to Non-HIV naïve patients with HCV genotype 2 or 3 who underwent treatment with IFN plus RBV for 24 weeks varied from 33% to 80% (Alves, De Azevedo et al, 2003;Acras, Pedroso et al, 2004;Borges, 2004;Villela-Nogueira, Perez et al, 2005;Parise, De Oliveira et al, 2006;Fachini, 2008;Almeida et al, 2009;Carneiro et al, 2010;Vigani et al, 2012). SVR rates from this Brazilian studies are very different from each other and below the main clinical trials found in literature (Manns et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Chronic Hepatitis C treatment for genotype 2 or 3 in Brazil: cost effectiveness analysis of peginterferon plus ribavirin as first choice treatment

Blatt

Storb

Mühlberger³

et al. 2014

Braz. J. Pharm. Sci.

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Brazilian Guidelines to HCV treatment (2007) recommended that the first choice treatment for patients with chronic hepatitis C (CHC) and genotype 2 or 3 is interferon alpha (IFN) plus ribavirin (RBV) for 24 weeks. The aim of this study is compare the cost and effectiveness to Hepatitis C treatment in patients with genotype 2 or 3 of peginterferon alpha (PEG) as the first choice of treatment within PEG for those that do not respond to IFN. The target population is CHC patients with genotype 2 or 3 in Brazil. The interventions are: PEG-SEC (first IFN plus RBV for 24 weeks, after, for non-responders and relapsers subsequently PEG plus RBV for 48 weeks); PEG-FIRST24 (PEG+RBV for 24 weeks). The type of the study is cost-effectiveness analysis. The data sources are: Effectiveness data from meta-analysis conducted on the Brazilian population. Treatment cost from Brazilian micro costing study is converted into USD (2010). The perspective is the Public Health System. The outcome measurements are Sustained Viral Response (SVR) and costs. PEG-FIRST24 (SVR: 87.8%, costs: USD 8,338.27) was more effective and more costly than PEG-SEC (SVR: 79.2%, costs: USD 5,852.99). The sensitivity analyses are: When SVR rates with IFN was less than 30% PEG-FIRST is dominant. On the other hand, when SVR with IFN was more then 75% PEG-SEC is dominant (SVR=88.2% and costs USD $ 3,753.00). PEG-SEC is also dominant when SVR to PEG24 weeks was less than 54%. In the Brazilian context, PEG-FIRST is more effective and more expensive than PEG-SEC. PEG-SEC could be dominant when rates of IFN therapy are higher than 75% or rates of PEG24 therapy are lower than 54%.Uniterms: Hepatitis C chronic/treatment. Interferon alpha/Hepatitis C treatment. Ribavirin/Hepatitis C treatment. Peginterferon alpha/Hepatitis C treatment. Hepatitis C/ treatment/cost-effectiveness evaluation.O protocolo brasileiro de tratamento da Hepatite C (2007) recomendava como primeira escolha para pacientes com hepatite C crônica e portadores de genótipo 2 ou 3 o tratamento com interferona alfa (IFN) associada à ribavirina (RBV), por 24 semanas. O objetivo deste estudo é comparar o custo e a efetividade para pacientes com hepatite C crônica e portadores do genótipo 2 ou 3 o uso de peguinterferon (PEG) como primeiro escolha com o PEG como secunda escolha para aqueles que não responderam ao tratamento com IFN. A população alvo compreende pacientes com hepatite C crônica portadores de genótipo 2 ou 3 no Brasil. As intervenções são: PEG-SEC (IFN + RBV por 24 semanas, para os não respondedores e recidivantes tratamento subsequente com PEG + RBV por 48 semanas; PEG-FIRST24 (PEG + RBV por 24 semanas). O tipo de estudo envolvido é Análise de Custo Efetividade. Os dados de efetividade são provenientes de um metanálise de estudos brasileiros e os dados de custo do tratamento de um estudo de custo do contexto brasileiro. A perspectiva é o Sistema Público de Saúde. Os desfechos avaliados foram Resposta Viral Sustentada (RVS) e Custos. 8%, costs: USD 8.338,27) foi mais efetivo e apresentou mai...

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Natural killer cell receptor and HLA-C gene polymorphisms among patients with hepatitis C: a comparison between sustained virological responders and non-responders

Abstract: Host genetic factors may be associated with a non-response to antiviral therapy. KIR2DL5 is a candidate gene involved in immunomodulation associated with non-response to antiviral therapy.

Cited by 24 publications

References 26 publications

Chronic hepatitis C treatment outcomes in low- and middle-income countries: a systematic review and meta-analysis

Chronic hepatitis C treatment outcomes in low- and middle-income countries: a systematic review and meta-analysis

KLRG1 Negatively Regulates Natural Killer Cell Functions through the Akt Pathway in Individuals with Chronic Hepatitis C Virus Infection

Chronic Hepatitis C treatment for genotype 2 or 3 in Brazil: cost effectiveness analysis of peginterferon plus ribavirin as first choice treatment

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