oalib
Search Results: 1 - 10 of 100 matches for " "
All listed articles are free for downloading (OA Articles)
Page 1 /100
Display every page Item
Sequence Heterogeneity in NS5A of Hepatitis C Virus Genotypes 2a and 2b and Clinical Outcome of Pegylated-Interferon/Ribavirin Therapy  [PDF]
Ahmed El-Shamy, Ikuo Shoji, Soo-Ryang Kim, Yoshihiro Ide, Susumu Imoto, Lin Deng, Seitetsu Yoon, Takashi Fujisawa, Satoshi Tani, Yoshihiko Yano, Yasushi Seo, Takeshi Azuma, Hak Hotta
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0030513
Abstract: Pegylated-interferon plus ribavirin (PEG-IFN/RBV) therapy is a current standard treatment for chronic hepatitis C. We previously reported that the viral sequence heterogeneity of part of NS5A, referred to as the IFN/RBV resistance-determining region (IRRDR), and a mutation at position 70 of the core protein of hepatitis C virus genotype 1b (HCV-1b) are significantly correlated with the outcome of PEG-IFN/RBV treatment. Here, we aimed to investigate the impact of viral genetic variations within the NS5A and core regions of other genotypes, HCV-2a and HCV-2b, on PEG-IFN/RBV treatment outcome. Pretreatment sequences of NS5A and core regions were analyzed in 112 patients infected with HCV-2a or HCV-2b, who were treated with PEG-IFN/RBV for 24 weeks and followed up for another 24 weeks. The results demonstrated that HCV-2a isolates with 4 or more mutations in IRRDR (IRRDR[2a]≥4) was significantly associated with rapid virological response at week 4 (RVR) and sustained virological response (SVR). Also, another region of NS5A that corresponds to part of the IFN sensitivity-determining region (ISDR) plus its carboxy-flanking region, which we referred to as ISDR/+C[2a], was significantly associated with SVR in patients infected with HCV-2a. Multivariate analysis revealed that IRRDR[2a]≥4 was the only independent predictive factor for SVR. As for HCV-2b infection, an N-terminal half of IRRDR having two or more mutations (IRRDR[2b]/N≥2) was significantly associated with RVR, but not with SVR. No significant correlation was observed between core protein polymorphism and PEG-IFN/RBV treatment outcome in HCV-2a or HCV-2b infection. Conclusion: The present results suggest that sequence heterogeneity of NS5A of HCV-2a (IRRDR[2a]≥4 and ISDR/+C[2a]), and that of HCV-2b (IRRDR[2b]/N≥2) to a lesser extent, is involved in determining the viral sensitivity to PEG-IFN/RBV therapy.
Four-week pegylated interferon -2a monotherapy for chronic hepatitis C with genotype 2 and low viral load: A pilot, randomized study  [cached]
Akihito Tsubota, Ken-ichi Satoh, Mashu Aizawa, Seishi Takamatsu, Yoshihisa Namiki, Toshifumi Ohkusa, Kiyotaka Fujise, Hisao Tajiri
World Journal of Gastroenterology , 2008,
Abstract: AIM: To assess the efficacy and advantages of 4-wk pegylated interferon α-2a (peg-IFN-α2a) monotherapy for chronic hepatitis C patients with strong predictors of sustained virologic response (SVR).METHODS: Patients (n = 33) with genotype 2 and low viral load (< 100 KIU/mL), who became HCV RNA negative after 1 wk of IFN treatment, were randomly allocated to receive a 4- or 12-wk treatment course at a ratio of 2:1, respectively, with a subsequent 24-wk follow-up period. Peg-IFN-α2a was administered subcutaneously at a dose of 180 μg or 90 μg once weekly. SVR was defined as absence of serum HCV RNA at the end of the follow-up period.RESULTS: All patients completed the treatment schedule, and more than half were symptom-free during the treatment. In the 4-wk treatment group, 20 of 22 (91%) patients achieved SVR. Two patients relapsed, but achieved SVR following re-treatment with peg-IFN-α2a alone. In the 12-wk treatment group, 11 of 11 (100%) patients attained SVR.CONCLUSION: Our results show that a 4-wk course of peg-IFN-α2a monotherapy can achieve a high SVR rate in “IFN-sensitive” patients, without negatively affecting outcome.
Pegylated interferon 2a and 2b in combination with ribavirin for the treatment of chronic hepatitis C in HIV infected patients
Ravinder Dhillon,Simona Rossi,Steven K Herrine
Therapeutics and Clinical Risk Management , 2008,
Abstract: Ravinder Dhillon, Simona Rossi, Steven K HerrineDepartment of Medicine, Division of Gastroenterology and Hepatology, Thomas Jefferson University, Philadelphia, PA, USAAbstract: Coinfection with hepatitis C virus (HCV) and HIV is an increasingly recognized clinical dilemma, particularly since the advent of highly active antiretroviral therapy. Several studies of this population have demonstrated both more rapid progression of liver disease and poorer overall prognosis compared to HCV monoinfected patients. Consensus guidelines, based primarily on the results of 4 major randomized trials, recommend treatment with peginterferon and ribavirin for 48 weeks in coinfected patients. However, this current standard of care is associated with lower response rates to therapy than those seen in monoinfected patients. Important predictors of response include HCV genotype, pretreatment HCV RNA level, and presence of rapid virologic response (RVR) and early virologic response (EVR). Use of weight-based ribavirin dosing appears to be safe and enhances the likelihood of sustained virologic response (SVR). Adverse effects most commonly encountered are anemia and weight loss. Mitochondrial toxicity can occur in the setting of concomitant nucleoside reverse transcriptase inhibitor use, especially didanosine, abacavir, and zidovudine, and these should be discontinued before initiation of ribavirin therapy. Discontinuation of therapy should be considered in patients failing to demonstrate EVR, though ongoing trials are investigating a potential role for maintenance therapy in these patients. Peginterferon combined with weight-based ribavirin is appropriate and safe for treatment of HCV in HIV – HCV coinfected patients. This review summarizes the data supporting these recommendations.Keywords: hepatitis C, human immunodeficiency virus, peginterferon, ribavirin
Hepatitis B Virus Genotype B and High Expression of Interferon Alpha Receptor β Subunit are Associated With Better Response to Pegylated Interferon Alpha 2a in Chinese Patients With Chronic Hepatitis B Infection
He-Bin Fan,Ya-Bin Guo,You-Fu Zhu,An-Shen Chen
Hepatitis Monthly , 2012,
Abstract: Background: Hepatitis B virus (HBV) is one of leading causes of various hepatic diseases including acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Hundreds of million people worldwide are infected by HBV, chronically.Objectives: This study in conducted to investigate the in uence of Hepatitis B virus (HBV) genotypes and type I IFN-αreceptor β subunit (IFNAR2) expression in liver on response to treatment with pegylated IFN-α-2a (Peg-IFN-α-2a) for chronic hepatitis B infection.Patients and Methods: In this study, 65 eligible patients with chronic hepatitis B disease were enrolled. HBV genotypes of these patients were analyzed by using PCR-RFLP of the surface gene of HBV. The expression of IFNAR2 in the liver was immune histochemically investigated using anti-IFNAR2 antibody. All immune histochemical slides were read semi-quantitatively by image analysis. Chronic hepatitis B patients were treated with Peg-IFN-α2a therapy for a 48-week period and followed up for 24 weeks. Baseline characteristics and sustained viral response (SVR) to Peg-IFN-α-2a therapy were evaluated.Results: 55 % of patients exhibited HBV genotype B and 31.7 % patients exhibited HBV genotypes C infections. After treatment with Peg-IFN-α-2a, SVR was achieved in 66.7 % of patients with HBV genotype B and in 26.3 % of patients with HBV genotype C (P = 0.009). Semiquantitative and the image analysis indicated by gray level values revealed a higher IFNAR2 expression in the group with severe in ammation (P < 0.001). Patients’ high IFNAR2 protein expression had a signi cant impact on SVR to Peg-IFN-α-2a therapy (P = 0.028).Conclusions: HBV genotype B and high expression of IFNAR2 in the liver of chronic hepatitis B patients are closely associated with better response to Peg-IFN-α-2a therapy in chronic hepatitis B disease.
Pegylated interferon alfa and ribavirin for children with chronic hepatitis C  [cached]
Irit Rosen,Michal Kori,Orly Eshach Adiv,Baruch Yerushalmi
World Journal of Gastroenterology , 2013, DOI: 10.3748/wjg.v19.i7.1098
Abstract: AIM: To study current treatment options for pediatric hepatitis C infection and their associated success rates. METHODS: We retrospectively reviewed charts of thirty children who had been treated with combination therapy of pegylated interferon alfa plus ribavirin for chronic hepatitis C infection. Patients had been treated with ribavirin (15 mg/kg per day) and either pegylated interferon alfa 2a (180 mg/m2 once weekly) or pegylated interferon alfa 2b (1.5 mg/kg once weekly). Patients’ follow-up included subjective assessment of complaints, physical examination including weight and height, as well as laboratory evaluations for viral load [before treatment, at 12 wk, and 6 mo following treatment completion, as determined by sustained viral response (SVR)], complete blood count, liver enzymes, alkaline phosphatase, bilirubin, renal function tests, and thyroid function tests. For patients not achieving a two log decrease in viral load at treatment week 12, treatment was discontinued and the patient was considered a treatment non-responder. RESULTS: Thirty children aged 3-18 years were included in the study. Twenty patients (11 males, 9 females) received pegylated interferon alfa 2b and ten patients (6 males, 4 females) received pegylated interferon alfa 2a. Twenty-three patients were infected with genotype 1, six patients were infected with genotype 3, and one patient was infected with genotype 2. Twenty patients (67%) achieved SVR. Treatment success rates were 90% with pegylated interferon alfa 2a vs 55% with pegylated interferon alfa 2b. Although a trend was noted for improved outcomes in the group receiving pegylated interferon alfa 2a, there were no statistically significant outcome differences between the two treatment groups (P = 0.1). Treatment success was 56.5% for patients infected with genotype 1 virus, compared to 100% for patients infected with other genotypes (P = 0.064). There was no difference in treatment response between males and females. A cut-off age of twelve years was used to dichotomize younger vs older participants; however, no difference in treatment response was observed between these groups. Using multivariate regression analysis, we could not determine predictors for achieving SVR from among the variables we examined (age, sex, and viral genotype). Although we noted a trend toward SVR with peginterferon alfa-2a, there was no statistical difference between the two peginterferons. A high incidence of adverse reactions to treatment was noted. Twenty-five patients (83%) suffered from at least one adverse reaction, but most experienc
Interstitial Pneumonitis after Combination Therapy with Pegylated Interferon α-2b and Ribavirin for Chronic Hepatitis C  [PDF]
Yung Che Chen,Sheng-Nan Lu,Meng-Chih Lin
Chang Gung Medical Journal , 2007,
Abstract: Pulmonary toxicity is a rare but potentially fatal side effect occurring during interferon(IFN) α treatment for chronic hepatitis C. We present a 47-year-old woman who had chronichepatitis C and was treated with pegylated IFN α-2b in combination with ribavirin, with agood virological response by week 10 of therapy. Then the patient began to complain of dyspneaon exertion and a dry cough. A diagnosis of interstitial pneumonitis was made accordingto the results of chest X-rays, high resolution computed tomography and bronchoalveolarlavage analysis. Pegylated IFN α-2b has a longer absorption and elimination half-lifethan conventional IFN α-2b and a comparable potency to conventional IFN α-2b. Althoughthe tolerability of pegylated IFN α is comparable to that of conventional IFN α, pulmonarytoxicity may occur more frequently with long-acting pegylated IFN α therapy at an inappropriatelyhigh dose. Based on a MEDLINE search up to 2004, we believe that this is the firstreported case of a patient recovering from interstitial pneumonitis associated with pegylatedIFN α-2b for chronic hepatitis C. Physicians should keep in mind the possibility of this complicationwhen treating chronic hepatitis C patients with pegylated IFN α-2b and ribavirincombinational therapy
Antiviral/immunomodulatory combination therapy: Pegylated interferon alpha 2a and ribavirin in patients with chronic hepatitis C virus infection  [PDF]
Deli? Dragan,Mitrovi? Nikola,Popovi? Nata?a,Uro?evi? Aleksandar
Srpski Arhiv za Celokupno Lekarstvo , 2012, DOI: 10.2298/sarh1210612d
Abstract: Introduction. Chronic hepatitis C virus (HCV) infection can progress to liver cirrhosis that causes bleeding from the gastrointestinal tract, liver failure and primary hepatocellular carcinoma. Use of standard therapeutic option consists of recombinant pegylated interferon alpha 2a/b with ribavirin in order to eradicate virus and prevent complications. Objective. The aim of investigation was to evaluate efficiency of combination therapy (pegylated interferon alpha 2a/b plus ribavirin) in patients with chronic HCV infection and to estimate predictive factors for successful treatment. Methods. A total of 387 patients with confirmed diagnosis of hepatitis C were evaluated (aged 18-65 years of both genders). Patients were treated with pegylated interferon alpha 2a/b and ribavirin according to a standard regimen lasting 24 or 48 weeks, dependent on virus genotype. Results. Negative HCV RNA (PCR assay) was recorded in 79.7% of patients at the end of treatment. Six months after completed therapy, negative HCV RNA, i.e. stained virologic response (SVR) was assessed in 70.5% of patients. Statistical summary of our results concerning SVR confirmed better efficiency of combination therapy for the following parameters compared to other investigated variables: age ≤40 (84.3% vs. 59.l%; p<0.0005), absence of cirrhosis (75.6% vs. 58.3%; p=0.003), lack of genotype 1 (86.6% vs. 61.8%; p<0.0005), and in patients who received full doses of pegylated interferon alpha 2a (78.3% vs. 63.3%; p=0.002). Conclusion. Combination therapy of recombinant pegylated interferon alpha 2a with ribavirin leads to SVR in the majority of treated patients (70.5%). Successful treatment depends on a variety of host and virus factors.
Pegylated interferon plus ribavirin for genotype Ib chronic hepatitis C in Japan  [cached]
Takayuki Kogure, Yoshiyuki Ueno, Koji Fukushima, Futoshi Nagasaki, Yasuteru Kondo, Jun Inoue, Yasunori Matsuda, Eiji Kakazu, Takeshi Yamamoto, Hiroyoshi Onodera, Yutaka Miyazaki, Hiromasa Okamoto, Takehiro Akahane, Tomoo Kobayashi, Yutaka Mano, Takao Iwa
World Journal of Gastroenterology , 2008,
Abstract: AIM: To evaluate the efficacy of pegylated interferon α-2b (peg-IFNα-2b) plus ribavirin (RBV) therapy in Japanese patients with chronic hepatitis C (CHC) genotype Ib and a high viral load.METHODS: One hundred and twenty CHC patients (58.3% male) who received peg-IFNα-2b plus RBV therapy for 48 wk were enrolled. Sustained virological response (SVR) and clinical parameters were evaluated.RESULTS: One hundred (83.3%) of 120 patients completed 48 wk of treatment. 53 patients (44.3%) achieved SVR. Early virological response (EVR) and end of treatment response (ETR) rates were 50% and 73.3%, respectively. The clinical parameters (SVR vs non-SVR) associated with SVR, ALT (108.4 IU/L vs 74.5 IU/L, P = 0.063), EVR (76.4% vs 16.4%, P < 0.0001), adherence to peg-IFN (≥ 80% of planned dose) at week 12 (48.1% vs 13.6%, P = 0.00036), adherence to peg-IFN at week 48 (54.7% vs 16.2%, P < 0.0001) and adherence to RBV at week 48 (56.1% vs 32.1%, P = 0.0102) were determined using univariate analysis, and EVR and adherence to peg-IFN at week 48 were determined using multivariate analysis. In the older patient group (> 56 years), SVR in females was significantly lower than that in males (17% vs 50%, P = 0.0262). EVR and adherence to Peg-IFN were demonstrated to be the main factors associated with SVR.CONCLUSION: Peg-IFNα-2b plus RBV combination therapy demonstrated good tolerability in Japanese patients with CHC and resulted in a SVR rate of 44.3%. Treatment of elderly female patients is still challenging and maintenance of adherence to peg-IFNα-2b is important in improving the SVR rate.
Pegylated Interferon-α2a Inhibits Proliferation of Human Liver Cancer Cells In Vitro and In Vivo  [PDF]
Hironori Kusano, Jun Akiba, Sachiko Ogasawara, Sakiko Sanada, Makiko Yasumoto, Masamichi Nakayama, Keiko Ueda, Kosuke Ueda, Takashi Kurita, Keita Todoroki, Yumi Umeno, Osamu Nakashima, Hirohisa Yano
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0083195
Abstract: Purpose We investigated the effects of pegylated interferon-α2a (PEG-IFN-α2a) on the growth of human liver cancer cells. Methods The effect of PEG-IFN-α2a on the proliferation of 13 liver cancer cell lines was investigated in vitro. Cells were cultured with medium containing 0–4,194 ng/mL of PEG-IFN-α2a, and after 1, 2, 3, or 4 days of culture, morphologic observation and growth assay were performed. After hepatocellular carcinoma (HCC) cells (HAK-1B and KIM-1) were transplanted into nude mice, various doses of PEG-IFN-α2a were subcutaneously administered to the mice once a week for 2 weeks, and tumor volume, weight, and histology were examined. Results PEG-IFN-α2a inhibited the growth of 8 and 11 cell lines in a time- and dose-dependent manner, respectively, although the 50% growth inhibitory concentrations of 7 measurable cell lines on Day 4 were relatively high and ranged from 253 ng/mL to 4,431 ng/mL. Various levels of apoptosis induction were confirmed in 8 cell lines. PEG-IFN-α2a induced a dose-dependent decrease in tumor volume and weight, and a significant increase of apoptotic cells in the tumor. Subcutaneous administration of clinical dose for chronic hepatitis C (3 μg/kg, 0.06 μg/mouse) was effective and induced about 30-50% reduction in the tumor volume and weight as compared with the control. Conclusions Although in vitro anti-proliferative effects of PEG-IFN-α2a were relatively weak, PEG-IFN-α2a induced strong anti-tumor effects on HCC cells in vivo. The data suggest potential clinical application of PEG-IFN-α2a for the prevention and treatment of HCC.
Pegylated interferon α-2b up-regulates specific CD8+ T cells in patients with chronic hepatitis B  [cached]
Ji Chen, Yan Wang, Xue-Jie Wu, Jun Li, Feng-Qin Hou, Gui-Qiang Wang.
World Journal of Gastroenterology , 2010,
Abstract: AIM: To investigate the effect of pegylated interferon (IFN) α-2b on specific CD8+ T lymphocytes in patients with chronic hepatitis B (CHB).METHODS: Twenty-one patients with CHB were treated with pegylated IFN α-2b. Periphery blood mononuclear cells were isolated from fresh heparinized blood by Ficoll-Hypaque density gradient centrifugation (density: 1.077 g/L, Pharmingen) at weeks 0, 4, 8, 12, and 24, respectively. Frequency of circulating hepatitis B virus (HBV) epitope-specific CD8 T cells was detected by flow cytometry. Cytokines were detected by cytometric bead assay.RESULTS: The frequency of circulating HBV core or env-specific CD8 T cells was higher (P < 0.05), the number of HBV core specific CD8 T cells was greater at week 24 (P < 0.05), the level of Th1-type cytokines [interleukin (IL)-12, tumor necrosis factor-α, and IFN-γ] was higher, while that of Th2-type cytokines (IL-4, IL-6, and IL-10) was lower in responders than in non-responders (P < 0.05) after pegylated IFN α-2b treatment. The IL-6 level was correlated with HBV DNA (r = 0.597, P = 0.04), while the inducible protein-10 (IP-10) level was correlated with serum alanine aminotransferase (ALT) (r = 0.545, P = 0.005). The IP-10 level at week 8 after pegylated IFN α-2b treatment could predict the normalization of ALT in CHB patients (positive predict value = 56%, negative predict value = 92%).CONCLUSION: Pegylated IFN α-2b can enhance the immune response of CHB patients by increasing the frequency of HBV specific CD8+ T cells and regulating the Th1/Th2 cytokines.
Page 1 /100
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.