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Tamai H, Shingaki N, Mori Y, Moribata K, Kawashima A, Maeda Y, Niwa T, Deguchi H, Inoue I, Maekita T, Iguchi M, Kato J, Ichinose M. Low-Dose Pegylated Interferon α-2b Plus Ribavirin for Elderly and/or Cirrhotic Patients with Genotype 2 Hepatitis C Virus. Gut Liver 2017; 10:617-23. [PMID: 26601828 PMCID: PMC4933424 DOI: 10.5009/gnl15193] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Revised: 06/16/2015] [Accepted: 06/25/2015] [Indexed: 12/11/2022] Open
Abstract
Background/Aims This study aimed to predict sustained viral response (SVR) to low-dose pegylated interferon (PEG-IFN) plus ribavirin of elderly and/or cirrhotic patients with genotype 2 hepatitis C virus (HCV) using viral response within 2 weeks. Methods Low-dose PEG-IFN-α-2b plus ribavirin was administered to 50 elderly and/or cirrhotic patients with genotype 2 HCV for 24 weeks. The dynamics of HCV RNA and HCV core antigen levels within 2 weeks were measured. Results The patients’ median age was 66 years. There were 21 male and 29 female patients. The median baseline HCV RNA level was 5.7 log IU/mL. Rapid viral response was achieved in 17 patients (34%), SVR in 28 (56%), and two (4%) discontinued treatment. Univariate analysis of factors contributing to SVR showed significant differences for sex, baseline virus level, and response within 4 weeks. When 40 fmol/L was set as the cutoff value for the core antigen level at 1 week, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for predicting SVR were 93%, 75%, 84%, 88%, and 85%, respectively. Conclusions Low-dose PEG-IFN plus ribavirin was a safe and cost-effective treatment for elderly and/or cirrhotic patients with genotype 2 HCV, and the viral response within 2 weeks was a useful predictor of SVR.
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Affiliation(s)
- Hideyuki Tamai
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Naoki Shingaki
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Yoshiyuki Mori
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Kosaku Moribata
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Akira Kawashima
- Department of Internal Medicine, Naga Municipal Hospital, Wakayama, Japan
| | - Yoshimasa Maeda
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Toru Niwa
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Hisanobu Deguchi
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Izumi Inoue
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Takao Maekita
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Mikitaka Iguchi
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Jun Kato
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Masao Ichinose
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
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Abstract
PEGylation is the covalent conjugation of PEG to therapeutic molecules. Protein PEGylation is a clinically proven approach for extending the circulation half-life and reducing the immunogenicity of protein therapeutics. Most clinically used PEGylated proteins are heterogeneous mixtures of PEG positional isomers conjugated to different residues on the protein main chain. Current research is focused to reduce product heterogeneity and to preserve bioactivity. Recent advances and possible future directions in PEGylation are described in this review. So far protein PEGylation has yielded more than 10 marketed products and in view of the lack of equally successful alternatives to extend the circulation half-life of proteins, PEGylation will still play a major role in drug delivery for many years to come.
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Cavalcante LN, Lyra AC. Predictive factors associated with hepatitis C antiviral therapy response. World J Hepatol 2015; 7:1617-31. [PMID: 26140082 PMCID: PMC4483544 DOI: 10.4254/wjh.v7.i12.1617] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 12/16/2014] [Accepted: 05/05/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection may lead to significant liver injury, and viral, environmental, host, immunologic and genetic factors may contribute to the differences in the disease expression and treatment response. In the early 2000s, dual therapy using a combination of pegylated interferon plus ribavirin (PR) became the standard of care for HCV treatment. In this PR era, predictive factors of therapy response related to virus and host have been identified. In 2010/2011, therapeutic regimens for HCV genotype 1 patients were modified, and the addition of NS3/4a protease inhibitors (boceprevir or telaprevir) to dual therapy increased the effectiveness and chances of sustained virologic response (SVR). Nevertheless, the first-generation triple therapy is associated with many adverse events, some of which are serious and associated with death, particularly in cirrhotic patients. This led to the need to identify viral and host predictive factors that might influence the SVR rate to triple therapy and avoid unnecessary exposure to these drugs. Over the past four years, hepatitis C treatment has been rapidly changing with the development of new therapies and other developments. Currently, with the more recent generations of pangenotipic antiviral therapies, there have been higher sustained virologic rates, and prognostic factors may not have the same importance and strength as before. Nonetheless, some variables may still be consistent with the low rates of non-response with regimens that include sofosbuvir, daclatasvir and ledipasvir. In this manuscript, we review the predictive factors of therapy response across the different treatment regimens over the last decade including the new antiviral drugs.
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Affiliation(s)
- Lourianne Nascimento Cavalcante
- Lourianne Nascimento Cavalcante, André Castro Lyra, Hospital Sao Rafael - Gastro-Hepatology Service, Salvador, Bahia 41253-190, Brazil
| | - André Castro Lyra
- Lourianne Nascimento Cavalcante, André Castro Lyra, Hospital Sao Rafael - Gastro-Hepatology Service, Salvador, Bahia 41253-190, Brazil
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Niederau C, Mauss S, Schober A, Stoehr A, Zimmermann T, Waizmann M, Moog G, Pape S, Weber B, Isernhagen K, Sandow P, Bokemeyer B, Alshuth U, Steffens H, Hüppe D. Predictive factors for sustained virological response after treatment with pegylated interferon α-2a and ribavirin in patients infected with HCV genotypes 2 and 3. PLoS One 2014; 9:e107592. [PMID: 25238535 PMCID: PMC4169557 DOI: 10.1371/journal.pone.0107592] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2014] [Accepted: 08/12/2014] [Indexed: 12/15/2022] Open
Abstract
Background Previous trials have often defined genotype 2 and 3 patients as an “easy to treat” group and guidelines recommend similar management. Aims The present study looks for differences between the two genotypes and analyzes predictive factors for SVR. Methods Prospective, community-based cohort study involving 421 physicians throughout Germany. The analysis includes 2,347 patients with untreated chronic HCV genotype 2 (n = 391) and 3 (n = 1,956) infection treated with PEG-IFN α-2a plus ribavirin between August 2007 and July 2012. Results When compared with genotype 2 patients, those with genotype 3 were younger, had a shorter duration of infection, lower values of total cholesterol, LDL cholesterol and BMI, a higher frequency of drug use as infection mode and male gender (p<0.0001, respectively), and a higher APRI score (p<0.005). SVR was higher in genotype 2 when compared with genotype 3 (64.7% vs. 56.9%, p = 0.004). By multivariate analysis of genotype 2 patients, low baseline γ -GT and RVR predicted SVR. In genotype 3 age ≤45 years, cholesterol>130 mg/dl, a low APRI score, and a γ-GT ≥3-times ULN, RVR, and RBV starting dose were associated with SVR by multivariate analysis. Conclusions The present study corroborates that liver fibrosis is more pronounced in genotype 3 vs. 2. SVR is higher in genotype 2 versus genotype 3 partly because of follow-up problems in genotype 3 patients, in particular in those infected by drug use. Thus, subgroups of genotype 3 patients have adherence problems and need special attention also because they often have significant liver fibrosis. Trial Registration Verband Forschender Arzneimittelhersteller e.V., Berlin, Germany ML21645 ClinicalTrials.gov NCT02106156
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Affiliation(s)
- Claus Niederau
- Clinic for Internal Medicine, St. Josef Hospital, Oberhausen, Germany
- * E-mail:
| | - Stefan Mauss
- Center for HIV and Hepatogastroenterology, Duesseldorf, Germany
| | | | - Albrecht Stoehr
- ifi-Institute for Interdisciplinary Medicine, Hamburg, Germany
| | - Tim Zimmermann
- 1st Medical Clinic, Dept. Gastroenterology and Hepatology, Johannes Gutenberg University of Mainz, Mainz, Germany
| | | | - Gero Moog
- Center of Gastroenterology, Kassel, Germany
| | - Stefan Pape
- Center of Gastroenterology, Paderborn, Germany
| | - Bernd Weber
- Competence Center for Addiction, Praxiszentrum Friedrichsplatz, Kassel, Germany
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Baseline serum cholesterol is associated with a response to pegylated interferon alfa-2b and ribavirin therapy for chronic hepatitis C genotype 2. Gastroenterol Res Pract 2012. [PMID: 23193392 PMCID: PMC3501951 DOI: 10.1155/2012/317580] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Background. HCV infection is associated with lipid disorders because this virus utilizes the host lipid metabolism to sustain its life cycle. Several studies have indicated that higher concentrations of serum cholesterol and LDL before treatment are important predictors of higher rates of sustained virological response (SVR). However, most of these studies involved patients infected with HCV genotype 1. Thus, we performed a multi-institutional clinical study to evaluate the impact of lipid profiles on SVR rates in patients with HCV genotype 2. Methods. A total of 100 chronic hepatitis C patients with HCV genotype 2 who received peg-IFN alfa-2b and ribavirin therapy were consecutively enrolled. The significance of age, sex, BMI, AST level, ALT level, WBC, hemoglobin, platelet count, gamma-glutamyltransferase, total cholesterol level (TC), LDL level, HCV RNA, and histological evaluation was examined for SVR using logistic regression analysis. Results. The 100 patients infected with HCV genotype 2 were divided into 2 groups, an SVR group and a non-SVR group. Characteristics of each group were subsequently compared. There was no significant difference in the level of HCV RNA, BMI, platelet, TG, or stage of fibrosis between the groups. However, there were significant differences in the levels of TC and LDL-C. In multivariate logistic regression analysis using baseline characteristics, high TC level was an independent and significant risk factor (relative risk 18.59, P = 0.015) for SVR. Conclusion. Baseline serum total cholesterol levels should be considered when assessing the likelihood of sustained treatment response following the course of peg-IFN and ribavirin therapy in patients with chronic HCV genotype 2 infection.
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Kanda T, Imazeki F, Azemoto R, Yonemitsu Y, Mikami S, Kita K, Takashi M, Sunaga M, Wu S, Nakamoto S, Tawada A, Arai M, Kato K, Yoshida Y, Koma Y, Fujiwara K, Fukai K, Suzuki N, Yokosuka O. Response to peginterferon-alfa 2b and ribavirin in Japanese patients with chronic hepatitis C genotype 2. Dig Dis Sci 2011; 56:3335-3342. [PMID: 21604145 DOI: 10.1007/s10620-011-1750-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2011] [Accepted: 05/05/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND The current standard treatment for patients infected with hepatitis C virus (HCV) of genotype 2 is the combination of peginterferon (PEG-IFN) plus ribavirin (RBV) for 24 weeks. AIMS We assessed the sustained virological response (SVR) rates in HCV genotype 2-infected Japanese patients in relation to the duration of treatment. METHODS Between 2006 and 2009, among 147 patients with HCV genotype 2-infection in Chiba Prefecture, 138 consecutive patients were finally enrolled. Twenty-one, 97 and 20 patients were treated with PEG-IFN-alfa 2b plus RBV for 16, 24 and 48 weeks, respectively. Epidemiological data and treatment outcomes were retrospectively evaluated. HCV RNA was measured with COBAS AMPLICOR HCV Monitor Test v. 2.0. RESULTS The overall SVR rate was 82.6% (114 of 138): treatment-naïve patients, 86.4% (89 of 103); patients with history of previous treatment, 71.4% (25 of 35). Patients treated for 16, 24 and 48 weeks obtained SVR rates of 66.6% (14 of 21), 86.5% (84 of 97) and 80.0 (16 of 20), respectively. CONCLUSIONS The SVR rates of PEG-IFN-alfa 2b plus RBV in Japanese patients were similar to those in previous studies. Combination treatment for 24 weeks for some patients infected with HCV genotype 2 may be superior to that for 16 weeks. More precise patient selection will be needed to shorten the combination treatment.
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Affiliation(s)
- Tatsuo Kanda
- Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
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