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Interleukin-28B genotype testing to determine response to the combination of pegylated-interferon and ribavirin for the treatment of hepatitis C virus.

ABSTRACT: Hepatitis C virus (HCV) is a bloodborne infection that is one of the leading causes of liver disease. If left untreated, HCV can lead to cirrhosis, hepatocellular carcinoma, and death. The current standard of care for HCV is a combination of pegylated-interferon (peg-IFN) and ribavirin (RBV) in which the goal of treatment is to decrease complications and death due to HCV. HCV displays genetic polymorphism, where patients with HCV genotype 1 may have higher viral replication rates and are less likely to respond to treatment. These patients require a longer duration of treatment and a higher RBV dose. The interleukin (IL) 28B genotype test is associated with a sustained virologic response (SVR), defined as an undetectable HCV ribonucleic acid (RNA) upon completion of treatment and 24 weeks thereafter.

SUBMITTER: Nguyen CM

PROVIDER: S-EPMC3024597 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Interleukin-28B genotype testing to determine response to the combination of pegylated-interferon and ribavirin for the treatment of hepatitis C virus.

Nguyen Christine M CM Mendes Margaret M Tsunoda Shirley S Ma Joseph D JD

PLoS currents 20110108

Hepatitis C virus (HCV) is a bloodborne infection that is one of the leading causes of liver disease. If left untreated, HCV can lead to cirrhosis, hepatocellular carcinoma, and death. The current standard of care for HCV is a combination of pegylated-interferon (peg-IFN) and ribavirin (RBV) in which the goal of treatment is to decrease complications and death due to HCV. HCV displays genetic polymorphism, where patients with HCV genotype 1 may have higher viral replication rates and are less li ...[more]

PMID: 21278901

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Interleukin-28B polymorphisms and response of chronic hepatitis C patients from Indonesia to pegylated interferon/ribavirin treatment.

Project description:This study demonstrated that Indonesian patients with chronic hepatitis C (mostly ethnic Java people) mostly were infected with hepatitis C virus (HCV) genotype 1; however, they carried mainly the major genotypes of interleukin 28B (IL-28B) single nucleotide polymorphisms (SNPs) (rs12979860 CC, rs11881222 TT, rs8103142 AA, and rs8099917 TT), and they mostly achieved sustained virological responses to pegylated interferon/ribavirin treatment.

| S-EPMC4042733 | biostudies-literature

The role of interleukin-28b gene polymorphisms in chinese patients with chronic hepatitis C treated with pegylated interferon and ribavirin.

Project description:BackgroundInterleukin-28B (IL28B) single nucleotide polymorphism (SNP) rs8099917 has been described to be associated with response to treatment with pegylated interferon and ribavirin (PEG-IFN/RBV) in patients with chronic hepatitis C from the North America, Europe, Asia countries like Japan and Taiwan. Whether this holds true for Chinese patients remains unknown.ObjectivesWe aimed to study the effects of IL28B rs8099917 on antiviral therapy responses in Chinese patients with hepatitis C.Patients and methodsIL28B rs8099917 was genotyped in 263 patients with hepatitis C virus (HCV) infection and 244 healthy controls in Tianjin, China using TaqMan SNP genotyping method. The roles of rs8099917 and clinical characteristics in antiviral treatment were analyzed by logistic regression.ResultsAmong 263 patients with chronic HCV infection, 223 had a TT genotype (84.8%). Frequencies of TG/GG genotypes in patients with hepatitis C were significantly different from those of healthy controls (15.2% vs. 9.0%; P = 0.033). Patients with HCV infection had a higher G allele frequency than healthy controls (7.8% vs. 4.7%; P = 0.044). Univariate analysis revealed no significant association between rs8099917 and sustained virological response (SVR) (P = 0.612). However, it was found that HCV genotypes 2a/3a, age, prothrombin time (PT), albumin (ALB) and cholesterol (CHO) were associated with SVR. In multivariate analysis, only ALB was significantly an independent predictor of SVR (OR = 1.223; 95%CI: 1.046-1.430; P = 0.011).ConclusionsIn contrast with T, rs8099917 G is a susceptible allele to HCV in China. ALB can independently predict SVR. Rs8099917 may play a quiet role to predict treatment response of patients with hepatitis C who received PEG-IFN/RBV therapy in China.

| S-EPMC4199147 | biostudies-literature

Polymorphism of IL-28B Gene (rs12979860) in HCV Genotype 1Patients Treated by Pegylated Interferon and Ribavirin.

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| S-EPMC5079454 | biostudies-literature

The interleukin 28B gene polymorphism, rs8099917, in patients with chronic hepatitis C and response to the treatment with pegylated interferon and ribavirin.

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| S-EPMC6421889 | biostudies-literature

Interferon-λ3 polymorphisms in pegylated-interferon-α plus ribavirin therapy for genotype-2 chronic hepatitis C.

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| S-EPMC4385537 | biostudies-literature

Deciphering the interleukin 28B variants that better predict response to pegylated interferon-? and ribavirin therapy in HCV/HIV-1 coinfected patients.

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Combination of sofosbuvir, pegylated-interferon and ribavirin for treatment of hepatitis C virus genotype 1 infection: a systematic review and meta-analysis.

Project description:BackgroundHepatitis C virus (HCV) infection is an important cause of chronic liver disease which has been affected 3% of world's population. Some studies have shown that adding Sofosbuvir (SOF), an HCV polymerase inhibitor to the conventional therapy of Pegylated-interferon (PegIFN) plus Ribavirin (RBV) can increase the rate of sustained virologic response (SVR) among HCV-infected patients. This study was conducted to determine the effect of combination therapy with PegIFN and RBV plus SOF for chronic hepatitis C genotype 1 infection using systematic review with meta-analysis.MethodsIn this study, electronic databases including PubMed, Scopus, Science Direct, and Web of Science were comprehensively searched using appropriate strategies containing all related keywords of "hepatitis C", "PegIFN", "RBV" and "SOF". Studies assessed the efficacy of combination therapy with PegIFN and RBV plus SOF for chronic hepatitis C genotype 1 infection were included in the meta-analysis.ResultsAfter screening of 757 records, we included five articles with total sample size of 411 to the meta-analysis. Based on the fixed-effect model (χ 2 = 5.29, P = 0.26 and I2 = 24.4%), pooled SVR rate for treatment regimen of PegIFN and RBV plus SOF was calculated as 88.54% (95% CI = 85.77%-91.32%).ConclusionsCombination therapy with PegIFN and RBV plus SOF results in high treatment response in patients with HCV genotype 1 infection.

| S-EPMC5397824 | biostudies-literature

Efficacy of 24-week pegylated interferon alpha and ribavirin combination therapy in highly selected patients infected with hepatitis C virus genotype 1.

Project description:BackgroundPrevious studies using pegylated interferon (Peg-IFN) and ribavirin (RBV) combination therapy suggested that patients with hepatitis C virus (HCV) genotype 1 and low pretreatment HCV RNA level who achieved rapid virological response (RVR) can be treated for 24 weeks without compromising sustained virological response (SVR) rate.ObjectivesThe current study aimed to investigate the efficacy of Peg-IFN-alfa-2a plus RBV administered for a 24-week treatment course in patients with chronic HCV genotype 1 infection and possessing the following criteria: low baseline serum HCV RNA level, absence of significant fibrosis and achievement of RVR.Patients and methodsIn this case-control study, 20 patients with HCV genotype 1 infection and favorable baseline characteristics and on-treatment response were treated with Peg-IFN and RBV for 24 weeks as the case group. Furthermore, 23 patients with the same characteristics who underwent a 48-week treatment course were selected as the control group.ResultsThe majority of patients had no fibrosis on liver elastography. There was no statistical difference regarding age, gender, alanine transaminase (ALT) level, rs12979860 polymorphism and the level of fibrosis between the two studied groups. All patients in the 24-week treatment course achieved SVR and all the subjects who received the 48-week treatment course achieved SVR as well (P > 0.99).ConclusionsThe current study confirmed that the efficacy of a 24-week regimen of Peg-IFN-alfa-2a plus RBV was similar to the 48-week treatment in the patients infected with HCV genotype 1, and low baseline HCV RNA level who achieved RVR. Response guided therapy can be efficient and cost-effective among the selected HCV genotype 1-infected patients.

| S-EPMC4330713 | biostudies-literature

Individualized treatment of chronic hepatitis C with pegylated interferon and ribavirin.

Project description:Chronic infection with hepatitis C virus (HCV) is a major public health problem, with perhaps 180 million people infected worldwide. A significant proportion of these will eventually develop clinical complications, such as cirrhosis, liver decompensation and hepatocellular carcinoma. Sustained virological response (SVR) to antiviral therapy is associated with improvement in liver histology and survival free of liver-related complications. Great effort has been made to improve SVR rate by adapting the duration of therapy according to HCV genotype and to on-treatment response. Rapid virological response (RVR, undetectable HCV RNA at week 4) usually has a high positive predictive value for achieving SVR and early virological response (EVR, ? 2 log reduction or undetectable HCV RNA at week 12) exhibits a high negative predictive value for non-response. Individualized approach can improve cost-effectiveness of HCV antiviral therapy by reducing side effects and the costs of therapy associated with unnecessary exposure to treatment and through extending therapy for those with unfavorable features. This article summarizes recent data on strategies of individualized treatment in naïve patients with mono-infection by the different HCV genotypes. The management of common side effects, the impact of HCV infection on health-related quality of life and the potential applications of host genomics in HCV therapy are also briefly discussed.

| S-EPMC3513206 | biostudies-other

The impact of interleukin 28b gene polymorphism on the virological response to combined pegylated interferon and ribavirin therapy in chronic HCV genotype 4 infected egyptian patients using data mining analysis.

Project description:BackgroundChronic HCV represents one of the common causes of chronic liver disease worldwide with Egypt having the highest prevalence, namely genotype 4. Interleukin IL-28B gene polymorphism has been shown to relate to HCV treatment response, mainly in genotype1.ObjectivesWe aim to evaluate the predictive power of the rs12979860 IL28B SNP and its protein for treatment response in genotype 4 Egyptian patients by regression analysis and decision tree analysis.Patients and methodsThe study included 263 chronic HCV Egyptian patients receiving peg-interferon and ribavirin therapy. Patients were classified into 3 groups; non responders (83patients), relapsers (76patients) and sustained virological responders (104 patients). Serum IL 28 B was performed, DNA was extracted and analyzed by direct sequencing of the SNP rs 12979860 of IL28B gene.ResultsCT, CC and TT represented 56 %, 25 % and 19% of the patients, respectively. Absence of C allele (TT genotype) was significantly correlated with the early failure of response while CC was associated with sustained virological response. The decision tree showed that baseline alpha fetoprotein (AFP ≤ 2.68 ng/ml) was the variable of initial split (the strongest predictor of response) confirmed by regression analysis. Patients with TT genotype had the highest probability of failure of response.ConclusionsAbsence of the C allele was significantly associated with failure of response. The presence of C allele was associated with a favorable outcome. AFP is a strong baseline predictor of HCV treatment response. A decision tree model is useful for predicting the probability of response to therapy.

| S-EPMC3776149 | biostudies-literature

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