Optimal Duration of Treatment for HCV Genotype 1 Infection in Slow Responders: A Meta-Analysis

Alavian, Seyed Moayed; Tabatabaei, Seyed Vahid; Behnava, Bita; Mahboobi, Nastaran

doi:10.5812/kowsar.1735143x.721

Cited by 7 publications

(4 citation statements)

References 53 publications

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“…Hepatitis C virus (HCV) is a major cause of chronic liver disease all-over the world ( 1 ). More than 130 million people are chronically infected with HCV who might progress to cirrhosis and hepatocellular carcinoma ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

The Role of Interferon Gamma Gene Polymorphism (+874A/T, +2109A/G, and -183G/T) in Response to Treatment Among Hepatitis C Infected Patients in Fars Province, Southern Iran

et al. 2014

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Background:Hepatitis C virus (HCV) infection as a worldwide health problem is associated with cirrhosis and hepatocellular carcinoma. With current treatment regimen, pegylated interferon (PEG-IFN) plus ribavirin, sustain virological response (SVR) is achieved in only 50% of infected individuals. In HCV infection, an inappropriate ratio of cytokines may affect the benefit of antiviral therapy. Given the polymorphisms in regulatory regions of cytokines genes may influence cytokines production.Objectives:We aimed to investigate both the frequency of genotypes and alleles of interferon gamma (IFN-γ) gene at +874A/T, +2109A/G, and -183G/T loci in HCV-infected patients and their associations with response to therapy.Patients and Methods:A total of 158 patients were included and treated with PEG-IFN plus ribavirin. The presence of HCV infection in patients was confirmed by reverse transcription polymerase chain reaction, and genomic DNA was extracted from peripheral leukocytes using salting out method. IFN-γ gene polymorphisms were identified by polymerase chain reaction using sequence specific primers and restriction fragment length polymorphism analysis on genomic DNA.Results:Of 158 patients, 110 (69.5%) subjects achieved SVR and 48 (30.5%) subjects did not respond to therapy. The frequency of AA genotype (P = 0.001; OR: 11.2; CI: 2.26-63.21) and A allele (P = 0.01; OR: 3.23; CI: 1.23 8.56) of IFN-γ gene at +2109 locus were significantly different between the responder and non-responder subjects infected with genotype 1. Regardless of HCV genotype, the frequency of AG genotype was also higher in responder group than those who did not respond to therapy (P = 0.041; OR: 05.05; CI: 1.05-33.25)). In case of IFN-γ gene at +874 locus, there was no difference in genotypes and alleles frequencies between the responder and non-responder subjects infected with HCV genotypes 1 and 3. Haplotype analysis showed no association between haplotypes and response to therapy. All participants had G/T genotype at -183 locus.Conclusions:Our findings indicate that heterogeneity at +2109 locus of IFN-γ gene but not at +874 locus could interfere with successful therapy in patients infected with HCV genotype 1.

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Section: Introductionmentioning

confidence: 99%

The Role of Interferon Gamma Gene Polymorphism (+874A/T, +2109A/G, and -183G/T) in Response to Treatment Among Hepatitis C Infected Patients in Fars Province, Southern Iran

et al. 2014

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“…The effect of several factors, such as HCV genotype, pretreatment HCV viral load, and stage of liver fibrosis, on the response to antiviral therapy, has been reported. Also, the type of prescribed interferon (2a versus 2b) ( 4 ), ribavirin dosage ( 5 ), and optimal duration of antiviral therapy have been recognized as other determinant factors of response to treatment ( 6 ). It has been seen that response rates are variable in different races.…”

Section: Introductionmentioning

confidence: 99%

Mysterious Linkages Between Hepatitis C Virus Genotypes, Interleukin-28B Genotypes and Viral Clearance- A Meta-Analysis

Aalaei‐Andabili¹,

Behnava²,

Salimi³

et al. 2014

Hepat Mon

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Background:Recent genome wide association studies (GWAS) have shown important roles of single nucleotide polymorphisms (SNP) near region of interleukin B 28 (IL28B) gene in spontaneous and drug-induced clearance of hepatitis C virus (HCV) in genotype 1 HCV infection.Objectives:This meta-analysis was designed to determine the world-wide distribution patterns of IL28B genotypes and alleles, and to find possible linkages between IL28B and HCV genotypes.Patients and Methods:Manual and electronic databases were searched. Critical appraisal was performed. According to the results of heterogeneity tests, we used fix/random model for the analysis. The data concerning patients’ ethnicity and HCV genotypes were analyzed by using statistical analysis software.Results:A total of 255 articles were found. After article review and quality assessment, 50 studies, including 18662 patients and 1313 healthy subjects, were analyzed. Presence of HCV genotype 3 versus genotype 1 was significantly associated with a higher frequency of CC genotype and C allele, with an odds ratio (OR) of 1.68 (95% CI: 1.44-1.99) and 1.49 (95% CI: 1.33-1.67), respectively. Prevalence of the rs12979860 CC genotype among genotype 1 HCV infected patients of Asian ethnicity was 69.48% (95% CI: 65.20-73.77), which was significantly higher than its prevalence [33.27% (95% CI: 28.88-37.67)] in the Caucasian genotype 1 HCV infected patients. Prevalence of rs12979860 TT genotype in the African-American genotype 1 HCV infected patients was the highest [36.20% (95% CI: 32.91-39.49)], and significantly different compared to all other ethnicities.Conclusions:There were significant linkages between HCV genotypes and IL28B genotypes/alleles. Patients with a favorable IL28B and genotypes 1 and 4 HCV infection stand a better chance to clear HCV in the acute phase.

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“…In the early 2000s, the structure of IFN was modified by adding polyethene glycol (PEG) chains [62][63][64][65][66][67][68]. Pegylation of IFN (PEGIFN) confers constant absorption, a longer half-life in serum and lower systemic clearance.…”

Section: Interferon α and Ribavirinmentioning

confidence: 99%

“…Pegylation of IFN (PEGIFN) confers constant absorption, a longer half-life in serum and lower systemic clearance. These changes allow sustained serum concentrations and improve the SVR when combined with RBV [62][63][64][65][66][67][68]. PEGIFN has two forms of presentation in HCV treatment: pegylated IFNα2a (PEG IFNα2a) and pegylated IFNα2b (PEG IFNα2b).…”

Section: Interferon α and Ribavirinmentioning

confidence: 99%

A Synopsis of Hepatitis C Virus Treatments and Future Perspectives

Medina,

García,

Crespo

et al. 2023

CIMB

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Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection with HCV can lead to liver cirrhosis or cancer. Although some immune-competent individuals can clear the virus, others develop chronic HCV disease due to viral mutations or an impaired immune response. IFNs type I and III and the signal transduction induced by them are essential for a proper antiviral effect. Research on the viral cycle and immune escape mechanisms has formed the basis of therapeutic strategies to achieve a sustained virological response (SVR). The first therapies were based on IFNα; then, IFNα plus ribavirin (IFN–RBV); and then, pegylated-IFNα-RBV (PEGIFNα-RIV) to improve cytokine pharmacokinetics. However, the maximum SVR was 60%, and several significant side effects were observed, decreasing patients’ treatment adherence. The development of direct-acting antivirals (DAAs) significantly enhanced the SVR (>90%), and the compounds were able to inhibit HCV replication without significant side effects, even in paediatric populations. The management of coinfected HBV–HCV and HCV–HIV patients has also improved based on DAA and PEG-IFNα-RBV (HBV–HCV). CD4 cells are crucial for an effective antiviral response. The IFNλ3, IL28B, TNF-α, IL-10, TLR-3, and TLR-9 gene polymorphisms are involved in viral clearance, therapeutic responses, and hepatic pathologies. Future research should focus on searching for strategies to circumvent resistance-associated substitution (RAS) to DAAs, develop new therapeutic schemes for different medical conditions, including organ transplant, and develop vaccines for long-lasting cellular and humoral responses with cross-protection against different HCV genotypes. The goal is to minimise the probability of HCV infection, HCV chronicity and hepatic carcinoma.

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Optimal Duration of Treatment for HCV Genotype 1 Infection in Slow Responders: A Meta-Analysis

Cited by 7 publications

References 53 publications

The Role of Interferon Gamma Gene Polymorphism (+874A/T, +2109A/G, and -183G/T) in Response to Treatment Among Hepatitis C Infected Patients in Fars Province, Southern Iran

The Role of Interferon Gamma Gene Polymorphism (+874A/T, +2109A/G, and -183G/T) in Response to Treatment Among Hepatitis C Infected Patients in Fars Province, Southern Iran

Mysterious Linkages Between Hepatitis C Virus Genotypes, Interleukin-28B Genotypes and Viral Clearance- A Meta-Analysis

A Synopsis of Hepatitis C Virus Treatments and Future Perspectives

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