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Brzdęk M, Zarębska-Michaluk D, Tomasiewicz K, Tudrujek-Zdunek M, Lorenc B, Mazur W, Berak H, Janocha-Litwin J, Klapaczyński J, Sitko M, Janczewska E, Dybowska D, Parfieniuk-Kowerda A, Piekarska A, Jaroszewicz J, Flisiak R. Effectiveness and safety of direct-acting antivirals in the therapy of HCV-infected elderly people. Minerva Med 2024; 115:266-276. [PMID: 38591836 DOI: 10.23736/s0026-4806.24.09238-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/10/2024]
Abstract
BACKGROUND The introduction of direct-acting antivirals (DAAs) with their effectiveness and safety has revolutionized the approach to treating hepatitis C virus (HCV) infections. Nevertheless, elderly patients have often been excluded from clinical trials, so the results of real-world studies are particularly important in the context of the geriatric population. The study aimed to analyze the effectiveness and safety of antiviral DAA treatment in HCV-infected patients over the age of 65, with notable inclusion of those over the age of 85. METHODS The analyzed patients were divided by age into three groups: group A (65-74 years), group B (75-84 years) and group C (85 years or older). Patients started DAA based therapy at 22 hepatology centers between July 2015 and December 2022. RESULTS A total of 3505 elderly patients were included in the analysis, and this group consisted of 2501 patients in group A, 893 in group B, and 111 in group C. The study population, regardless of age, was dominated by women. Patients had a high prevalence of comorbidities (84.9%, 92.2%, and 93.7%, respectively) as well as a high rate of concomitant medications. The sustained virological response was 97.9% in groups A and B and 100% in group C. The therapy was well-tolerated, with a comparable safety profile observed in all analyzed groups. CONCLUSIONS DAA-based therapies are highly effective and well tolerated by the elderly patients, including those over 85. Age should not be a barrier to treatment, but careful management is necessary.
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Affiliation(s)
- Michał Brzdęk
- Department of Infectious Diseases and Allergology, Jan Kochanowski University, Kielce, Poland -
| | | | | | | | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Medical University Gdansk, Gdansk, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Clinical University of Silesia in Katowice, Chorzów, Poland
| | - Hanna Berak
- Daily Department, Hospital for Infectious Diseases, Warsaw, Poland
| | - Justyna Janocha-Litwin
- Department of Infectious Diseases and Hepatology, Wroclaw Medical University, Wroclaw, Poland
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, The National Institute of Medicine of the Ministry of Interior and Administration, Warsaw, Poland
| | - Marek Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University, Krakow, Poland
| | - Ewa Janczewska
- Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia in Katowice, Bytom, Poland
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Nicolaus Copernicus University, Bydgoszcz, Poland
| | - Anna Parfieniuk-Kowerda
- Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Lodz, Lodz, Poland
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia in Katowice, Bytom, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland
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Benito JM, García-Samaniego J, García M, Madejón A, Martín-Carbonero L, Cabello A, Álvarez B, Górgolas M, Rallón N. Both Hepatitis C Virus-Specific T Cell Responses and IL28B rs12979860 Single-Nucleotide Polymorphism Genotype Influence Antihepatitis C Virus Treatment Outcome in Patients with Chronic Hepatitis C. J Interferon Cytokine Res 2017; 37:278-286. [PMID: 28440692 DOI: 10.1089/jir.2016.0078] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Despite new treatments for hepatitis C virus (HCV) infection, IFNα-based regimens still have clinical relevance in special populations of patients and remain the only therapeutic option for many patients. We sought to elucidate the interplay between two relevant factors (IL28B polymorphism and T cell immune responses) involved in the outcome of this therapy in HCV-infected patients. We evaluated 38 patients infected with HCV genotype 1-17 coinfected with HIV-who were undergoing a full course of pegIFNα/RBV therapy. The interdependence and roles of T cell-mediated immune responses and IL28B rs12979860 single-nucleotide polymorphism genotype as predictors of virological response to anti-HCV treatment in patients with chronic hepatitis C were evaluated using nonparametric tests. Factors associated with rapid virological response (RVR) in univariate analysis were presence of CD4 T cell response against NS3 HCV protein, low baseline HCV-RNA, and IL28B CC genotype. Factors associated with sustained virological response (SVR) in univariate analysis were IL28B CC genotype, low baseline HCV-RNA, and presence of CD4 response against NS2. In the multivariate analysis, low baseline HCV-RNA and NS3-specific CD4 response showed a clear trend toward association with RVR (P = 0.09 and P = 0.07, respectively). Regarding SVR, IL28B CC genotype was the strongest predictor (P = 0.02), with presence of NS2-specific CD4 response showing a clear trend (P = 0.09). HCV-specific T cell response influences the outcome of pegIFNα/RBV therapy regardless of IL28B genotype. HCV-specific T cell responses (adaptive immunity) seem to influence viral clearance both in the short and long term during therapy (RVR and SVR), whereas the influence of the IL28B genotype (innate immunity) may be more relevant to the long-lasting therapeutic effect (SVR).
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Affiliation(s)
- José M Benito
- 1 IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid , Madrid, Spain
- 2 Hospital Universitario Rey Juan Carlos , Móstoles, Spain
| | | | - Marcial García
- 1 IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid , Madrid, Spain
- 2 Hospital Universitario Rey Juan Carlos , Móstoles, Spain
| | - Antonio Madejón
- 3 Hepatology Unit, Hospital Universitario La Paz , Madrid, Spain
- 4 CIBERehd , Madrid, Spain
| | | | - Alfonso Cabello
- 5 Infectious Diseases Unit, Hospital Universitario Fundación Jiménez Díaz , Madrid, Spain
| | - Beatriz Álvarez
- 5 Infectious Diseases Unit, Hospital Universitario Fundación Jiménez Díaz , Madrid, Spain
| | - Miguel Górgolas
- 5 Infectious Diseases Unit, Hospital Universitario Fundación Jiménez Díaz , Madrid, Spain
| | - Norma Rallón
- 1 IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid , Madrid, Spain
- 2 Hospital Universitario Rey Juan Carlos , Móstoles, Spain
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Anuja K, Roy S, Ghosh C, Gupta P, Bhattacharjee S, Banerjee B. Prolonged inflammatory microenvironment is crucial for pro-neoplastic growth and genome instability: a detailed review. Inflamm Res 2016; 66:119-128. [PMID: 27653961 DOI: 10.1007/s00011-016-0985-3] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Revised: 08/25/2016] [Accepted: 08/31/2016] [Indexed: 02/08/2023] Open
Abstract
INTRODUCTION Chronic inflammation can affect the normal cell homeostasis and metabolism by rendering the cells susceptible to genomic instability that may lead to uncontrolled cellular growth and proliferation ensuing tumorigenesis. The causal agents for inflammation may be pathogenic infections like microbial agents ranging from viruses to bacteria. These infections lead to DNA damage or disruption of normal cell metabolism and alter the genome integrity. FINDINGS In this review, we have highlighted the role of recurrent infections in tumor microenvironment can lead to recruitment of pro-inflammatory cells, cytokines and growth factors to the site of inflammation. This makes the environment rich in cytokines, chemokines, DNA-damaging agents (ROS, RNS) and growth factors which activate DNA damage response pathway and help in sustained proliferation of the tumor cells. In any inflammatory response, the production of cytokines and related signaling molecules is self-regulating and limiting. But in case of neoplastic risk, deregulation of these factors may lead to abnormalities and related pathogenesis. CONCLUSION The scope of the present review is to explore the probable mechanistic link and factors responsible for chronic inflammation. The relation between chronic inflammation and DNA damage response was further elucidated to understand the mechanism by which it makes the cells susceptible to carcinogenesis.
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Affiliation(s)
- Kumari Anuja
- Molecular Stress and Stem Cell Biology Group, School of Biotechnology, KIIT University, Bhubaneshwar, Odisha, 751024, India
| | - Souvick Roy
- Molecular Stress and Stem Cell Biology Group, School of Biotechnology, KIIT University, Bhubaneshwar, Odisha, 751024, India
| | - Chinmoy Ghosh
- Molecular Stress and Stem Cell Biology Group, School of Biotechnology, KIIT University, Bhubaneshwar, Odisha, 751024, India
| | - Priya Gupta
- Department of Molecular Biology and Bioinformatics, Tripura University (A Central University), Suryamaninagar, Agartala, Tripura, 799022, India
| | - Surajit Bhattacharjee
- Department of Molecular Biology and Bioinformatics, Tripura University (A Central University), Suryamaninagar, Agartala, Tripura, 799022, India.
| | - Birendranath Banerjee
- Molecular Stress and Stem Cell Biology Group, School of Biotechnology, KIIT University, Bhubaneshwar, Odisha, 751024, India.
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Molecular docking, 2D and 3D-QSAR studies of new indole-based derivatives as HCV-NS5B polymerase inhibitors. JOURNAL OF THE IRANIAN CHEMICAL SOCIETY 2015. [DOI: 10.1007/s13738-015-0654-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Roeder C, Jordan S, Schulze zur Wiesch J, Pfeiffer-Vornkahl H, Hueppe D, Mauss S, Zehnter E, Stoll S, Alshuth U, Lohse AW, Lueth S. Age-related differences in response to peginterferon alfa-2a/ribavirin in patients with chronic hepatitis C infection. World J Gastroenterol 2014; 20:10984-10993. [PMID: 25152602 PMCID: PMC4138479 DOI: 10.3748/wjg.v20.i31.10984] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2014] [Revised: 02/20/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the safety and efficacy of pegylated interferon alfa-2a and ribavirin therapy in elderly patients with chronic hepatitis C infection.
METHODS: Patients characteristics, treatment results and safety profiles of 4859 patients with hepatitis c virus (HCV) infection receiving treatment with pegylated interferon alfa-2a and ribavirin were retrieved from a large ongoing German multicentre non-interventional study. Recommended treatment duration was 24 wk for GT 2 and GT 3 infection and 48 wk for GT 1 and GT 4 infection. Patients were stratified according to age (< 60 years vs≥ 60 years). Because of limited numbers of liver biopsies for further assessment of liver fibrosis APRI (aspartate aminotransferase - platelet ratio index) was performed using pre-treatment laboratory data.
RESULTS: Out of 4859 treated HCV patients 301 (6.2%) were ≥ 60 years. There were more women (55.8% vs 34.2%, P < 0.001) and predominantly GT 1 (81.4% vs 57.3%, P < 0.001) infected patients in the group of patients aged ≥ 60 years and they presented more frequently with metabolic (17.6% vs 4.5%, P < 0.001) and cardiovascular comorbidities (32.6% vs 6.7%, P < 0.001) and significant fibrosis and cirrhosis (F3/4 31.1% vs 14.0%, P = 0.0003). Frequency of dose reduction and treatment discontinuation were significantly higher in elderly patients (30.9% vs 13.7%, P < 0.001 and 47.8% vs 30.8%, P < 0.001). Main reason for treatment discontinuation was “virological non-response” (26.6% vs 13.6%). Sustained virological response (SVR) rates showed an age related difference in patients with genotype 1 (23.7% vs 43.7%, P < 0.001) but not in genotype 2/3 infections (57.7% vs 64.6%, P = 0.341). By multivariate analysis, age and stage of liver disease were independent factors of SVR.
CONCLUSION: Elderly HCV patients differ in clinical characteristics and treatment outcome from younger patients and demand special attention from their practitioner.
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Abstract
Hepatitis B virus (HBV), hepatitis C virus (HCV), human papillomavirus (HPV), and Epstein-Barr virus (EBV) contribute to about 10-15 % global burden of human cancers. Conventional chemotherapy or molecular target therapies have been used to treat virus-associated cancers. However, a more proactive approach would be the use of antiviral treatment to suppress or eliminate viral infections to prevent the occurrence of cancer in the first place. Antiviral treatments against chronic HBV and HCV infections have achieved this goal, with significant reduction in the incidence of hepatocellular carcinoma in treated patients. Antiviral treatments for EBV, Kaposi's sarcoma-associated herpesvirus (KSHV), and human T-cell lymphotropic virus type 1 (HTLV-1) had limited success in treating refractory EBV-associated lymphoma and post-transplant lymphoproliferative disorder, KSHV-associated Kaposi's sarcoma in AIDS patients, and HTLV-1-associated acute, chronic, and smoldering subtypes of adult T-cell lymphoma, respectively. Therapeutic HPV vaccine and RNA-interference-based therapies for treating HPV-associated cervical cancers also showed some encouraging results. Taken together, antiviral therapies have yielded promising results in cancer prevention and treatment. More large-scale studies are necessary to confirm the efficacy of antiviral therapy. Further investigation for more effective and convenient antiviral regimens warrants more attention.
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Affiliation(s)
- Wei-Liang Shih
- Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan
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Brennan BJ, Xu ZX, Grippo JF. Effect of peginterferon alfa-2a (40KD) on cytochrome P450 isoenzyme activity. Br J Clin Pharmacol 2013; 75:497-506. [PMID: 22765278 DOI: 10.1111/j.1365-2125.2012.04373.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2012] [Accepted: 06/25/2012] [Indexed: 12/29/2022] Open
Abstract
AIM Pegylated interferon-based therapy is recommended for treatment of hepatitis C virus (HCV) infection. Because interferons are known to down-regulate hepatic cytochrome P450 (CYP) enzymes, which are involved in drug metabolism and clearance, there is a need to investigate the effect of peginterferon (PEG-IFN) alfa-2a (40KD) on the activity of these enzymes in vivo. METHODS Fourteen healthy, male volunteers aged 18 to 45 years were recruited into an open label, two period, single centre study in which CYP enzyme activity was measured by administration of the selectively metabolized probe drugs theophylline (CYP1A2), tolbutamide (CYP2C9), mephenytoin (CYP2C19), debrisoquine (CYP2D6) and dapsone (CYP3A4) on day 1 of the study. PEG-IFN alfa-2a (40KD) 180 μg was given subcutaneously each week from day 15 to 36, and probe drugs were re-administered on day 37. Probe drugs and metabolites were quantified in plasma or urine samples and used to derive pharmacokinetic parameters. RESULTS PEG-IFN alfa-2a (40KD) significantly increased the area under the serum drug concentration vs. time curve (AUC(0,∞)) for theophylline by 24%, with a reduction in the mean oral clearance of theophylline of 20%. There were no effects on the pharmacokinetics of any of the other probe drugs. The incidence of adverse events was as expected in subjects receiving pegylated interferon. CONCLUSION These results suggest there may be an inhibitory effect of PEG-IFN alfa-2a (40KD) on CYP1A2. PEG-IFN alfa-2a (40KD) had no effect on CYP2C9, CYP2C19, CYP2D6 or CYP3A4 in healthy subjects.
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Affiliation(s)
- Barbara J Brennan
- Department of Clinical Pharmacology, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA.
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Zhang L, Han F, Zhang D, Dou XG. Mutations in different regions of the genome of hepatitis C virus genotype 1b and association with response to interferon therapy. Int J Mol Med 2012; 30:1438-42. [PMID: 23064792 DOI: 10.3892/ijmm.2012.1155] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2012] [Accepted: 06/18/2012] [Indexed: 01/30/2023] Open
Abstract
The aim of this study was to investigate the association of mutations in the E2/NS1 [hypervariable regions 1 and 2 (HVR1 and HVR2)] and NS5A regions of the hepatitis C virus (HCV) genome and the effectiveness of interferon (IFN) therapy, and assess whether the degree of heterogeneity of HCV quasispecies predicts response to IFN treatment. Fourteen patients infected with HCV genotype 1b (HCV-1b) who were treated with pegylated IFN-α-2a and ribavirin for 24 weeks, were studied. E2/NS1 and NS5A gene segments were amplified by reverse-transcription polymerase chain reaction. HCV quasispecies heterogeneity in the E2/NS1 region was determined by cloning and sequencing. Mutations in the NS5A region were detected by direct sequencing. The heterogeneity of HCV quasispecies in the HVR1 was significantly greater in the non-responder group than in the responder group, but was not significant for HVR2 or NS5A. The correlation between mutations in IFN sensitivity-determining region (ISDR, NS5A2209-2248) and IFN sensitivity could not be supported. The degree of quasispecies heterogeneity in HVR1, but not in HVR2 and NS5A, may be predictive of response to IFN therapy. An ISDR may not apply to patients infected with HCV-1b.
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Affiliation(s)
- Lin Zhang
- Department of Infectious Disease, Sheng Jing Hospital of China Medical University, Shenyang 110004, P.R. China
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Antiviral activity against the hepatitis C virus (HCV) of 1-indanone thiosemicarbazones and their inclusion complexes with hydroxypropyl-β-cyclodextrin. Eur J Pharm Sci 2012; 47:596-603. [DOI: 10.1016/j.ejps.2012.07.018] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2012] [Revised: 06/14/2012] [Accepted: 07/18/2012] [Indexed: 12/21/2022]
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Aituov B, Duisembekova A, Bulenova A, Alibek K. Pathogen-driven gastrointestinal cancers: Time for a change in treatment paradigm? Infect Agent Cancer 2012; 7:18. [PMID: 22873119 PMCID: PMC3508868 DOI: 10.1186/1750-9378-7-18] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2012] [Accepted: 07/27/2012] [Indexed: 02/06/2023] Open
Abstract
The regulation of cancerous tumor development is converged upon by multiple pathways and factors. Besides environmental factors, gastrointestinal (GI) tract cancer can be caused by chronic inflammation, which is generally induced by bacteria, viruses, and parasites. The role of these inducers in cancer development, cell differentiation and transformation, cell cycle deregulation, and in the expression of tumor-associated genes cannot be ignored. Although Helicobacter pylori activates many oncogenic pathways, particularly those in gastric and colorectal cancers, the role of viruses in tumor development is also significant. Viruses possess significant oncogenic potential to interfere with normal cell cycle control and genome stability, stimulating the growth of deregulated cells. An increasing amount of recent data also implies the association of GI cancers with bacterial colonization and viruses. This review focuses on host-cell interactions that facilitate primary mechanisms of tumorigenesis and provides new insights into novel GI cancer treatments.
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Affiliation(s)
- Bauyrzhan Aituov
- Nazarbayev University, 53 Kabanbay Batyr Avenue, Astana 010000, Kazakhstan
| | - Assem Duisembekova
- Nazarbayev University, 53 Kabanbay Batyr Avenue, Astana 010000, Kazakhstan
| | - Assel Bulenova
- Nazarbayev University, 53 Kabanbay Batyr Avenue, Astana 010000, Kazakhstan
| | - Kenneth Alibek
- Nazarbayev University, 53 Kabanbay Batyr Avenue, Astana 010000, Kazakhstan
- Republican Scientific Center for Emergency Care, 3 Kerey and Zhanibek Khan Street, Astana 010000, Kazakhstan
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Li L, Huang L, Lemos HP, Mautino M, Mellor AL. Altered tryptophan metabolism as a paradigm for good and bad aspects of immune privilege in chronic inflammatory diseases. Front Immunol 2012; 3:109. [PMID: 22593757 PMCID: PMC3350084 DOI: 10.3389/fimmu.2012.00109] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2012] [Accepted: 04/17/2012] [Indexed: 01/01/2023] Open
Abstract
The term "immune privilege" was coined to describe weak immunogenicity (hypo-immunity) that manifests in some transplant settings. We extended this concept to encompass hypo-immunity that manifests at local sites of inflammation relevant to clinical diseases. Here, we focus on emerging evidence that enhanced tryptophan catabolism is a key metabolic process that promotes and sustains induced immune privilege, and discuss the implications for exploiting this knowledge to improve treatments for hypo-immune and hyper-immune syndromes using strategies to manipulate tryptophan metabolism.
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Affiliation(s)
- Lingqian Li
- Immunotherapy Center, Georgia Health Sciences University Augusta, GA, USA
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Brennan BJ, Morcos PN, Wang K, Blotner SD, Morrison R, Hagedorn CH, Marbury TC, Sulkowski M, Grippo JF. The pharmacokinetics of peginterferon alfa-2a and ribavirin in African American, Hispanic and Caucasian patients with chronic hepatitis C. Aliment Pharmacol Ther 2012; 35:1209-20. [PMID: 22469033 DOI: 10.1111/j.1365-2036.2012.05079.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2011] [Revised: 01/23/2012] [Accepted: 03/07/2012] [Indexed: 12/18/2022]
Abstract
BACKGROUND Amongst Caucasian, Hispanic and African Americans with genotype 1 hepatitis C virus (HCV), there is a wide variation in response to treatment with peginterferon alfa-2a (PEG-IFN alfa-2a) and ribavirin. AIM To evaluate the pharmacokinetics (PK) of PEG-IFN alfa-2a and ribavirin among these three groups. METHODS Forty-seven patients with genotype 1 CHC (17 African Americans, 14 Hispanics and 16 Caucasians) received 8 weeks of PEG-IFN alfa-2a (180 μg/week) and ribavirin (1000 or 1200 mg/day). PEG-IFN alfa-2a serum concentrations and ribavirin plasma concentrations were measured following the first dose and at week 8. Pharmacokinetic parameters (C(max), T(max), AUC, CL/F) were estimated using noncompartmental methods. RESULTS There was no difference in the pharmacokinetic parameters for PEG-IFN alfa-2a following single-dose or steady-state administration between African American or Hispanic patients compared with Caucasian patients. Ribavirin pharmacokinetic parameters were similar between Hispanic and Caucasian patients for single-dose and steady-state administration. The single-dose C(max) was 33% lower (P < 0.05) in African American compared with Caucasian patients. Other ribavirin single-dose and steady-state pharmacokinetic parameters were slightly decreased (approximately 20% lower) in African American patients, but were not considered clinically meaningful. CONCLUSIONS No differences were observed in PEG-IFN alfa-2a pharmacokinetic parameters between African American or Hispanic patients compared with Caucasian patients. For ribavirin, no differences were observed in pharmacokinetic parameters between Hispanic and Caucasian patients. While a trend towards increased ribavirin clearance and decreased exposure was observed in African American patients vs. Caucasian patients, the differences were small and not considered clinically meaningful (Clinical Trial Number: NP17354).
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