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The influence of anti-HBc status on the sustained virological response rate in HCV-infected patients treated with pegylated interferon alfa 2 and ribavirin. Clin Exp Hepatol 2016; 2:155-160. [PMID: 28856281 PMCID: PMC5497428 DOI: 10.5114/ceh.2016.63873] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Accepted: 10/16/2016] [Indexed: 12/19/2022] Open
Abstract
Aim of the study To determine the influence of HBsAg and HBeAg negative but anti-HBc positive status on the sustained virological response (SVR) rate in HCV-infected patients treated with pegylated interferon alfa 2 (Peg-IFNα-2) and ribavirin (RBV). Material and methods The study was based on the retrospective analysis of medical records of HCV-infected patients who started Peg-IFNα and RBV treatment between 1 January 2011 and 31 December 2013 at the 1st and 2nd Department of Infectious Diseases of the Regional Hospital in Wrocław, Poland. Results Among 240 patients included in the analysis 99 were anti-HBc positive and 141 anti-HBc negative. In the genotype 1, anti-HBc positive group the SVR rate was 47% and in the anti-HBc negative group it was 42.7% (p = 0.591). In the genotype 3, anti-HBc positive group the SVR rate was 60% and in anti-HBc negative patients it was 63.2% (p = 0.79). Differences in SVR rates between anti-HBc positive and negative groups were not statistically significant. None of the anti-HBc positive patients developed reactivation of HBV infection during or in the 24 weeks following the end of treatment. Conclusions Anti-HBc determination does not seem to be useful in predicting treatment outcome of conventional Peg-IFNα/RBV therapy in patients infected with HCV genotypes 1 and 3.
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Imran M, Manzoor S, Azam S, Resham S. Genetic variant of IL28B rs12979860, as predictive marker of interferon-based therapy in Pakistani population. APMIS 2015; 123:342-9. [PMID: 25703417 DOI: 10.1111/apm.12365] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Accepted: 12/17/2014] [Indexed: 12/12/2022]
Abstract
Hepatitis C virus (HCV) genotypes and genetic variants of interleukin 28B (IL28B) are significantly associated with interferon plus ribavirin treatment of HCV infection. We investigated the distribution of HCV genotypes and single-nucleotide polymorphisms (SNPs) of IL28B (rs12979860 and rs8099917) in Pakistani population. IL28B genotyping was performed by allele-specific PCR and restriction fragment length polymorphism PCR in 140 chronic hepatitis C patients (CHC) and 120 healthy controls. HCV genotype 3 (HCVG3) was the most prevalent genotype, 71.4% (n = 100/140) and with the highest treatment response of 90% (n = 90/100). The overall treatment response of all the HCV genotypes was 82% (n = 115/140). The distribution of IL28B rs12979860CC genotype in treatment responder and non-responder groups was 40.8% (n = 47/115) and 16% (n = 4/25) respectively. IL28B rs12979860CC genotype demonstrated a significant correlation (p = 0.019) with interferon-based therapy of HCV infection. However, there was no observed association of IL28B rs8099917 polymorphism with treatment response in CHC patients (p = 0.264). In conclusion, HCV genotypes and IL28B rs12979860 are predictive markers for the efficiency of interferon plus ribavirin combinational therapy of HCV infection. We recommend the inclusion of testing for these markers in the clinical criteria for decision making for HCV therapy in Pakistani population.
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Affiliation(s)
- Muhammad Imran
- Atta-ur-Rahman School of Applied Bio-Sciences, Department of Healthcare Biotechnology, National University of Sciences and Technology (NUST), Islamabad, Pakistan
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Romero-Gómez M, Turnes J, Ampuero J, Oyagüez I, Cuenca B, Gonzalez-Garcia J, Muñoz-Molina B, Aguilar R, Leal S, Planas R, Garcia-Samaniego J, Diago M, Crespo J, Calleja JL, Casado MA, Sola R. Prediction of week 4 virological response in hepatitis C for making decision on triple therapy: the Optim study. PLoS One 2015; 10:e0122613. [PMID: 25826755 PMCID: PMC4426774 DOI: 10.1371/journal.pone.0122613] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2014] [Accepted: 02/23/2015] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND Virological response to peginterferon + ribavirin (P+R) at week 4 can predict sustained virological response (SVR). While patients with rapid virological response (RVR) do not require triple therapy, patients with a decline <1 log10 IU/ml HCVRNA (D1L) should have treatment discontinued due to low SVR rate. AIM To develop a tool to predict first 4 weeks' viral response in patients with hepatitis C genotype 1&4 treated with P+R. METHODS In this prospective and multicenter study, HCV mono-infected (n=538) and HCV/HIV co-infected (n=186) patients were included. To develop and validate a prognostic tool to detect RVR and D1L, we segregated the patients as an estimation cohort (to construct the model) and a validation cohort (to validate the model). RESULTS D1L was reached in 509 (80.2%) and RVR in 148 (22.5%) patients. Multivariate analyses demonstrated that HIV co-infection, Forns' index, LVL, IL28B-CC and Genotype-1 were independently related to RVR as well as D1L. Diagnostic accuracy (AUROC) for D1L was: 0.81 (95%CI: 0.76 ̶ 0.86) in the estimation cohort and 0.71 (95%CI: 0.62 ̶ 0.79) in the validation cohort; RVR prediction: AUROC 0.83 (95%CI: 0.78 ̶ 0.88) in the estimation cohort and 0.82 (95%CI: 0.76 ̶ 0.88) in the validation cohort. Cost-analysis of standard 48-week treatment indicated a saving of 30.3% if the prognostic tool is implemented. CONCLUSIONS The combination of genetic (IL28B polymorphism) and viral genotype together with viral load, HIV co-infection and fibrosis stage defined a tool able to predict RVR and D1L at week 4. Using this tool would be a cost-saving strategy compared to universal triple therapy for hepatitis C.
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Affiliation(s)
- Manuel Romero-Gómez
- UCM Digestive Diseases & ciberehd, Valme University Hospital,
Sevilla, Spain
- * E-mail:
| | - Juan Turnes
- Complejo Hospitalario de Pontevedra, Pontevedra, Spain
| | - Javier Ampuero
- UCM Digestive Diseases & ciberehd, Valme University Hospital,
Sevilla, Spain
| | - Itziar Oyagüez
- Pharmacoeconomics & Outcomes Research Iberia, Madrid,
Spain
| | | | | | | | | | | | - Ramon Planas
- Hospital Germans Trias i Pujol & ciberehd, Badalona, Barcelona,
Spain
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Akkarathamrongsin S, Payungporn S, Thong VD, Poovorawan K, Prapunwattana P, Poovorawan Y, Tangkijvanich P. Early viral kinetics during hepatitis C virus genotype 6 treatment according to IL28B polymorphisms. World J Gastroenterol 2014; 20:10599-10605. [PMID: 25132781 PMCID: PMC4130872 DOI: 10.3748/wjg.v20.i30.10599] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 02/21/2014] [Accepted: 05/28/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the early viral kinetics and interleukin-28B (IL28B) polymorphisms of hepatitis C genotype 6 during pegylated interferon and ribavirin therapy. METHODS Sixty-five patients with chronic hepatitis C virus (HCV) infection treated with pegylated interferon and ribavirin (PEG-IFN/RBV) were included, of whom 15 (23.1%), 16 (24.6%) and 34 (52.3%) patients were infected with hepatitis C genotype 1 (HCV-1), genotype 3 (HCV-3) and genotype 6 (HCV-6), respectively. Serum HCV-RNA levels were measured frequently during the first 4-wk of therapy. DNA extracted from samples was analyzed for the IL28B single nucleotide polymorphism (SNP) rs12979860 by polymerase chain reaction and direct sequencing. RESULTS During the first 4-wk of therapy, the mean viral decline for patients with HCV-6 (5.55 ± 1.82 log₁₀IU/mL) was comparable to that of patients with HCV-3 (5.55 ± 1.82 log₁₀IU/mL vs 5.86 ± 1.02 log₁₀IU/mL, P = 0.44) and was significantly higher than patients with HCV-1 (5.55 ± 1.82 log₁₀IU/mL vs 4.23 ± 1.99 log₁₀IU/mL, P = 0.04). In the HCV-6 group, the first phase (days 0-2) viral decline was significantly higher in patients with the favorable rs12979860 CC than non-CC genotypes (2.46 ± 1.01 log₁₀IU/mL/wk vs 1.70 ± 0.67 log₁₀IU/mL, respectively, P = 0.045). A statistically insignificant decrease in the second-phase (days 7-28) decline was also found in patients with the CC genotype than those with the non-CC genotype, though not significantly different (1.24 ± 0.64 log₁₀IU/mL/wk vs 0.80 ± 0.65 log₁₀IU/mL/wk, respectively, P = 0.172). At baseline, the SNP genotype was an independent predictor of rapid virological response but not of sustained virological response. CONCLUSION The IL28B genotype was linked to an impact on early viral kinetics in response to PEG-IFN/RBV therapy in HCV-6 infected patients.
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Beisel C, Heuer M, Otto B, Jochum J, Schmiedel S, Hertling S, Degen O, Lüth S, van Lunzen J, Schulze zur Wiesch J. German cohort of HCV mono-infected and HCV/HIV co-infected patients reveals relative under-treatment of co-infected patients. AIDS Res Ther 2014; 11:16. [PMID: 25006340 PMCID: PMC4086688 DOI: 10.1186/1742-6405-11-16] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2013] [Accepted: 06/17/2014] [Indexed: 12/16/2022] Open
Abstract
Background Current German and European HIV guidelines recommend early evaluation of HCV treatment in all HIV/HCV co-infected patients. However, there are still considerable barriers to initiate HCV therapy in everyday clinical practice. This study evaluates baseline characteristics, “intention-to-treat” pattern and outcome of therapy of HCV/HIV co-infected patients in direct comparison to HCV mono-infected patients in a “real-life” setting. Methods A large, single-center cohort of 172 unselected HCV patients seen at the Infectious Diseases Unit at the University Medical Center Hamburg-Eppendorf from 2000–2011, 88 of whom HCV/HIV co-infected, was retrospectively analyzed by chart review with special focus on demographic, clinical and virologic aspects as well as treatment outcome. Results Antiviral HCV combination therapy with PEG-interferon plus weight-adapted ribavirin was initiated in 88/172 (52%) patients of the entire cohort and in n = 36 (40%) of all HCV/HIV co-infected patients (group A) compared to n = 52 (61%) of the HCV mono-infected group (group B) (p = 0.006). There were no significant differences of the demographics or severity of the liver disease between the two groups with the exception of slightly higher baseline viral loads in group A. A sustained virologic response (SVR) was observed in 50% (n = 18) of all treated HIV/HCV co-infected patients versus 52% (n = 27) of all treated HCV mono-infected patients (p = 0.859). Genotype 1 was the most frequent genotype in both groups (group A: n = 37, group B: n = 49) and the SVR rates for these patients were only slightly lower in the group of co-infected patients (group A: n = 33%, group B: 40% p = 0.626). During the course of treatment HCV/HIV co-infected patients received less ribavirin than mono-infected patients. Conclusion Overall, treatment was only initiated in half of the patients of the entire cohort and in an even smaller proportion of HCV/HIV co-infected patients despite comparable outcome (SVR) and similar baseline characteristics. In the light of newer treatment options, greater efforts to remove the barriers to treatment that still exist for a great proportion of patients especially with HIV/HCV co-infection have to be undertaken.
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Miyauchi T, Kanda T, Imazeki F, Mikata R, Tawada A, Arai M, Fujiwara K, Nakamoto S, Wu S, Tanaka T, Miyamura T, Kimura M, Hirai Y, Takashi M, Mikami S, Sugiura N, Natsuki Y, Azemoto R, Suzuki N, Yokosuka O. Response to peginterferon-alpha 2b and ribavirin in Japanese patients with chronic hepatitis C genotype 1. Hepatol Int 2013; 7:144-152. [DOI: 10.1007/s12072-012-9349-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Gheit SA, Keddeas MW, Safwat E. Rapid virological response as a predictor of a sustained virological response in Egyptian patients with chronic hepatitis C genotype 4. EGYPTIAN LIVER JOURNAL 2013. [DOI: 10.1097/01.elx.0000424248.63976.02] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Guedj J, Dahari H, Pohl RT, Ferenci P, Perelson AS. Understanding silibinin's modes of action against HCV using viral kinetic modeling. J Hepatol 2012; 56:1019-1024. [PMID: 22245888 PMCID: PMC3328661 DOI: 10.1016/j.jhep.2011.12.012] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2011] [Revised: 10/31/2011] [Accepted: 12/08/2011] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Legalon® SIL (SIL) is a chemically hydrophilized version of silibinin that has exhibited high antiviral effectiveness against hepatitis C virus (HCV). Its main mode of action (MOA) remains unclear, with contradicting in vitro studies supporting either suppression of entry and cell-to-cell spread or suppression of viral RNA synthesis as the main MOA. We sought to provide new insights into SIL's MOA in HCV genotype-1/4 patients receiving intravenous SIL monotherapy for 7 days via mathematical modeling. METHODS Changes in HCV RNA in 25 patients receiving 10, 15, or 20mg/kg/day of SIL were analyzed and modeled using viral kinetic methods. RESULTS In 15 patients, the virus declined in a biphasic manner, in which a sharp drop between days 0 and 2 was followed by a slower second phase of decline. In 10 patients, the initial decline was weaker and the virus declined in a single phase over the 7-day period. The blocking production effectiveness, ε, was dose-dependent with mean ε=0.49 and 0.89 in the 10 or 15 and 20mg/kg/day dosing groups, respectively (p=0.02). The effectiveness of blocking viral infection, η, was estimated as 0.60 with no significant differences across dosing groups. For all patients, the mean rate of viral load decline measured between days 2 and 7 was high (0.3 log(10)IU/ml/day), i.e., 4-fold higher than typically observed during the 2nd phase of (pegylated)-interferon-α±ribavirin treatment. CONCLUSIONS Modeling HCV kinetics in vivo suggests that SIL may block both viral infection and viral production/release with its main dose-dependent effect being blocking viral production/release.
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Affiliation(s)
- Jeremie Guedj
- Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
| | - Harel Dahari
- Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA; Department of Medicine, University of Illinois at Chicago, IL 60612, USA
| | - Ralf T Pohl
- Rottapharm Madaus, Madaus GmbH, Colonia Allee 15, Cologne 51067, Germany
| | - Peter Ferenci
- Internal Medicine 3, Department of Gastroenterology and Hepatology, Medical University of Vienna, Austria
| | - Alan S Perelson
- Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
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Laufer N, Bolcic F, Rolón MJ, Martinez A, Reynoso R, Pérez H, Salomón H, Cahn P, Quarleri J. HCV RNA decline in the first 24 h exhibits high negative predictive value of sustained virologic response in HIV/HCV genotype 1 co-infected patients treated with peginterferon and ribavirin. Antiviral Res 2011; 90:92-7. [PMID: 21376083 PMCID: PMC3102437 DOI: 10.1016/j.antiviral.2011.02.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2010] [Revised: 02/17/2011] [Accepted: 02/24/2011] [Indexed: 12/19/2022]
Abstract
BACKGROUND Treatment with Peg-interferon and ribavirin (PEG-IFN/RBV) for HIV patients co-infected with hepatitis C virus (HCV) genotype 1 has suboptimal rates of response. Viral kinetics has emerged as one of the best prognostic factors of treatment outcome. METHODS Twenty HIV/HCV genotype 1 co-infected patients in treatment with PEG-IFN/RBV, had blood drawn at baseline, 24 h, 4, 12, 24, 48, and 72 weeks. HCV-RNA levels were evaluated at each time point. ROC curves were used to evaluate the log10 HCV-RNA decay at 24 h that exhibits the best predictive value of achieving response. Genomic characterization of HCV NS5A at both interferon sensitivity-determining region (ISDR) and protein-kinase binding (PKRBD) domains were performed in order to evaluate its heterogeneity and association with 24 h HCV-RNA decay and SVR. RESULTS Non-responder patients exhibited a mean of 0.7 log10 (SD 0.74 log10) HCV-RNA decay at 24 h, whereas responder-patients presented 1.6 log10 (SD 0.28 log10), p = 0.04. A reduction in HCV viral load from baseline to 24 h of < 1.4 had a negative predictive value for achieving SVR of 100% and a positive predictive value of 50%. HCV genotype 1 isolates from patients with a decrease of HCV-RNA at 24 h > 1.4 log10, exhibited 3.1(SD 1.5) amino acids substitutions in ISDR and 4.8(SD 2.3) in PKRBD regions and 1.6(SD 0.7) and 2.4(SD 1.3), respectively, in those patients presenting lower reduction in HCV-RNA. CONCLUSIONS HIV/HCV genotype 1 co-infected patients with a decrease in HCV-VL at 24 h > 1.4 log10 are more likely to achieve SVR when treated with PEG-IFN/RBV than those with lower levels of HCV-RNA decay. Along with other host-related and viral-related prognostic factors in HIV/HCV co-infected patients, this very early time point of evaluation could be of relevance in the management of HCV-specific treatment.
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Affiliation(s)
- N Laufer
- Centro Nacional de Referencia para el SIDA, Universidad de Buenos Aires, Paraguay 2155, Buenos Aires, Argentina.
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