Meta-analysis Shows Extended Therapy Improves Response of Patients With Chronic Hepatitis C Virus Genotype 1 Infection
ABSTRACT Clinical trials provided conflicting results about whether extended duration of treatment with pegylated interferon-alfa (pegIFN-alfa) and ribavirin (more than 48 weeks) improves rates of sustained virologic response (SVR) in patients infected with hepatitis C virus (HCV) genotype 1 and slow virologic response. We performed a meta-analysis to determine the overall impact of extended treatment, compared with standard treatment, on virologic response rates in these patients.
We performed a literature search to identify randomized controlled trials (RCTs) that included monoinfected, treatment-naive patients infected with HCV genotype 1; data were compared between slow responding patients treated with pegIFN-alfa-2a/b plus ribavirin for 48 weeks and those that received extended treatment (as much as 72 weeks). End points included SVR rates, end-of-treatment (EOT) response and relapse rates; they were calculated according to the DerSimonian-Laird estimate.
Six RCTs assessed the benefits of extended treatment with pegIFN-alfa-2a/b and ribavirin in treatment-naive patients with HCV genotype 1 that were slow responders (n = 669). The extended treatment significantly improved SVR rates in slow responders, compared with the standard of care (14.7% increase in overall SVR; 95% confidence interval, 4%-25.5%; P = .0072). Rates of viral relapse were significantly reduced by extended treatment, but EOT response rates were similar. The frequency of voluntary treatment discontinuation, but not of serious adverse events, was significantly increased by extended therapy.
Extending the duration of treatment with pegIFN-alfa-2a/b and ribavirin in patients with HCV genotype 1 and a slow response to therapy improves the rate of SVR.
SourceAvailable from: Rosario Lopez-Rodriguez[Show abstract] [Hide abstract]
ABSTRACT: The aim of this study was to analyse the distribution of KIR haplotypes and the KIR2DL2/3 alleles in chronic HCV-infected patients in order to establish the influence on the response to pegylated interferon plus ribavirin classical treatment. The alleles study of previously associated KIR2DL2/3 showed that KIR2DL2*001 was more frequent in non-SVR (NSVR) (42.2% vs. 27.5%, p<0.05) and KIR2DL3*001 was associated with sustained viral response (SVR) (41.6% vs. 61.2%, p<0.005). The KIR2DL3*001-HLA-C1 association was also significant (24.5% vs. 45.7%, p<0.001). From the frequencies of KIR obtained, 35 genotypes were assigned on the basis of previous studies. The centromeric A/A genotype was more frequent in SVR (44.1% vs. 34.5%, p<0.005) and the centromeric B/B genotype was found to be significantly more frequent in NSVR (20.9% vs. 11.2%, p<0.001). The logic regression model showed the importance of KIR genes in predicting the response to combined treatment, since the positive predictive value (PPV) was improved (from 55.9% to 75.3%) when the analysis of KIR was included in addition to the IFNL3 rs12979860 polymorphism. The study of KIR receptors may be a powerful tool for predicting the combined treatment response in patients with chronic HCV infection in association with the determination of IFNL3 polymorphism.PLoS ONE 06/2014; 9(6):e99426. DOI:10.1371/journal.pone.0099426 · 3.53 Impact Factor
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ABSTRACT: Asia is endemic for hepatitis C virus (HCV) infection, which is the leading cause of cirrhosis, hepatic decompensation, hepatocellular carcinoma, and liver transplantation worldwide. HCV has six major genotypes and each HCV genotype has its specific geographic distribution. HCV genotypes 1, 2, 3, and 6 are common in Asia. The aim of HCV treatment is to eradicate the virus by effective therapeutic agents; viral clearance is durable after long-term post-treatment follow-up. In most Asian countries, peginterferon alfa (PEG-IFN α) in combination with ribavirin remains the standard of care, and the overall sustained viral response (SVR) rate in Asian HCV patients is higher than that in Western patients. The differences are most significant in patients with HCV genotype 1 (HCV-1) infection, which is attributed to the higher frequency of IFN-responsive or favorable interleukin-28B (IL-28B) genotype in Asian populations than in other ethnic populations. In addition, the introduction of response-guided therapy, where the optimized treatment duration is based on the early viral kinetics during the first 12 weeks of treatment, increases the SVR rate. Recently, telaprevir or boceprevir-based triple therapy was found to further improve the SVR rate in treated and untreated HCV-1 patients and has become the new standard of care in Western and some Asian countries. Many novel direct-acting antiviral agents, either in combination with PEG-IFN α plus ribavirin or used as IFN-free regimens are under active investigation. At the time of this writing, simeprevir and sofosbuvir have been approved in the US. Because the SVR rates in Asian HCV patients receiving PEG-IFN α plus ribavirin therapy are high, health care providers should judiciously determine the clinical usefulness of these novel agents on the basis of treatment duration, anticipated viral responses, patient tolerance, financial burdens, and drug accessibility.International Journal of Nanomedicine 01/2014; 9:2051-2067. DOI:10.2147/IJN.S41822 · 4.20 Impact Factor
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ABSTRACT: Objective To review and compare side effects of hepatitis C treatment with pegylated interferon and ribavirin at the CRIE of the Hospital Mário Covas (Santo André), São Paulo, Brazil, from February 23 to May 5, 2011. Methods Cross-sectional study through questionnaire, with a nonprobability sample comprised of 340 patients that had received at least one dose of the medication. Results Side effects presented were fatigue (82.9%), arthralgia and/or myalgia (76.8%), weight loss (71.8%), headache (67.6%), listlessness (65.9%), depression and/or irritability (64.4%), itching (60.6%), fever (59.1%), alopecia (51.5%), dry cough (34.1%), nausea (11.7%), inappetence (11.7%), and dizziness (7.9%). Up to 19 symptoms were reported during treatment. Only four patients (1.2%) did not present side effects. When comparing the types of interferon, it was observed that alpha-2b caused an average of 8.01 symptoms per patient, while alpha-2a was responsible for an average of 7.50 symptoms. Patients using interferon alpha-2b showed more fever, weight loss, headache, arthralgia and/or myalgia, fatigue, listlessness, depression and/or irritability, and dry cough than patients using alpha-2a, who had more alopecia and itching. Conclusion The study shows a high morbidity related to the treatment, as only 1.2% of the patients showed no side effects. In the sample, the pegylated interferon alpha-2b was responsible for higher prevalence of fever and weight loss when compared to alpha-2a, and this was a statistically significant relation (p < 0.05).09/2012; 58(5):543–549. DOI:10.1590/S0104-42302012000500010