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Zayed N, Gamal Eldeen H, Elmakhzangy H, Seif M, El-Akel W, Awad T, Esmat G, Mabrouk M. Therapeutic outcome of 6198 interferon-naïve Egyptian patients with chronic hepatitis C: a real-life experience and lessons to be learned in DAAs' era. J Viral Hepat 2016; 23:506-11. [PMID: 26936687 DOI: 10.1111/jvh.12514] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2015] [Accepted: 01/14/2016] [Indexed: 12/15/2022]
Abstract
Antiviral therapy for HCV infection has been validated in randomized controlled clinical trials, but its value in the real world is less well studied. There is relatively little data on real-world responses to interferon-based therapies for patients with genotype 4 infection. We aimed to examine experience with large-scale access to antiviral therapy in chronic HCV in a real-life clinical setting in Egypt. Detailed pretreatment data of 6198 IFN-naïve chronic HCV patients who had received PEG-IFN/RBV therapy at Cairo-Fatemic Hospital, Egypt, between 2009 and 2012 were obtained from the HCV database. At week 12, 95.7% of patients had undetectable HCV RNA, and by week 24 and 48, breakthrough was 6% and 4%, respectively. However, 43.7% of patients discontinued treatment prematurely, and intent to treat end of treatment response was 44.6% (79.3% per protocol). Sustai-ned response data were available from only 1281 patients and was 84.9%. Haematological abnormalities were comparable in patients who did or did not comply with therapy. This is the first real-world, large-scale experience of antiviral therapy in chronic HCV in Egypt. Suboptimal response in HCV predominantly genotype 4 was mainly driven by noncompliance as well as gaps in the healthcare system leading to treatment discontinuation. These results need to be considered in the era of all oral antiviral regimes.
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Affiliation(s)
- N Zayed
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - H Gamal Eldeen
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - H Elmakhzangy
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - M Seif
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - W El-Akel
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - T Awad
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt.,Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Rigshospitalet, Copenhagen, Denmark
| | - G Esmat
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - M Mabrouk
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
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Du NN, Peng ZG, Bi CW, Tang S, Li YH, Li JR, Zhu YP, Zhang JP, Wang YX, Jiang JD, Song DQ. N-substituted benzyl matrinic acid derivatives inhibit hepatitis C virus (HCV) replication through down-regulating host heat-stress cognate 70 (Hsc70) expression. PLoS One 2013; 8:e58675. [PMID: 23516533 PMCID: PMC3597726 DOI: 10.1371/journal.pone.0058675] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2012] [Accepted: 02/05/2013] [Indexed: 01/25/2023] Open
Abstract
Heat-stress cognate 70 (Hsc70) is a host factor that helps hepatitis C virus (HCV) to complete its life cycle in infected hepatocytes. Using Hsc70 as a target for HCV inhibition, a series of novel N-substituted benzyl matrinic/sophoridinic acid derivatives was synthesized and evaluated for their anti-HCV activity in vitro. Among these analogues, compound 7c possessing N-p-methylbenzyl afforded an appealing ability to inhibit HCV replication with SI value over 53. Furthermore, it showed a good oral pharmacokinetic profile with area-under-curve (AUC) of 13.4 µM·h, and a considerably good safety in oral administration in mice (LD50>1000 mg/kg). As 7c suppresses HCV replication via an action mode distinctly different from that of the marketed anti-HCV drugs, it has been selected as a new mechanism anti-HCV candidate for further investigation, with an advantage of no or decreased chance to induce drug-resistant mutations.
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Affiliation(s)
- Na-Na Du
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Zong-Gen Peng
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Chong-Wen Bi
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Sheng Tang
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Ying-Hong Li
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Jian-Rui Li
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Yan-Ping Zhu
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Jing-Pu Zhang
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Yan-Xiang Wang
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Jian-Dong Jiang
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
- State Key Laboratory of Bioactive Substance and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- * E-mail: (J-DJ); (D-QS)
| | - Dan-Qing Song
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
- * E-mail: (J-DJ); (D-QS)
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Innes HA, Hutchinson SJ, Allen S, Bhattacharyya D, Bramley P, Carman B, Delahooke TES, Dillon JF, Goldberg DJ, Kennedy N, Mills PR, Morris J, Morris J, Robertson C, Stanley AJ, Hayes P. Ranking predictors of a sustained viral response for patients with chronic hepatitis C treated with pegylated interferon and ribavirin in Scotland. Eur J Gastroenterol Hepatol 2012; 24:646-655. [PMID: 22433796 DOI: 10.1097/meg.0b013e32835201a4] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES From the literature on the hepatitis C virus, the existence of a gap between a sustained virologic response (SVR) attainable in randomized clinical trials (RCTs) versus routine practice is not clear. Further, in terms of the pretreatment prediction of SVR, to date, studies have focused only on reporting the magnitude of association (MOA) between each predictor and an SVR. They fail to acknowledge that a predictor with a large MOA is of little value to clinicians if it has low variability in the treatment population. METHODS Hepatitis C virus clinical databases were used to derive a large, representative cohort of Scottish pegylated interferon and ribavirin initiates. RESULTS Overall, 39% [123/315, 95% confidence interval (CI) 34-45%] of genotype 1 and 70% (414/594, 95% CI 66-73%) of genotype 2/3 patients achieved an SVR; this compares with the pooled estimates of 47% for genotype 1 (95% CI 41-52%) and 80% for genotype 2/3 (95% CI 75-85%) RCT participants. Significant predictors of SVR identified from logistic regression were ranked on the basis of the akaike information criteria (reflecting an approach that will account for each predictor's MOA and variability) as follows: (i) genotype, % increase in akaike information criteria of the final model when variables are excluded, 58.49%; (ii) γ-glutamyl transferase, 18.64%; (iii) platelet count, 6.48%; (iv) alanine aminotransferase quotient, 4.63%; (v) ever infected with hepatitis B virus, 4.31% and (vi) sex, 3.10%. CONCLUSION (i) The proportion of patients attaining an SVR in Scottish routine practice is marginally lower than in RCTs and (ii) other than genotype, γ-glutamyl transferase emerges as a valuable predictor of an SVR in routine practice. Further, we demonstrate an approach to more clearly discern the predictive value of response predictors.
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Affiliation(s)
- Hamish A Innes
- Department of Mathematics and Statistics, University of Strathclyde, Scotland, UK.
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Kramer JR, Kanwal F, Richardson P, Mei M, El-Serag HB. Gaps in the achievement of effectiveness of HCV treatment in national VA practice. J Hepatol 2012; 56:320-5. [PMID: 21756855 DOI: 10.1016/j.jhep.2011.05.032] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2011] [Revised: 05/02/2011] [Accepted: 05/20/2011] [Indexed: 12/19/2022]
Abstract
BACKGROUND & AIMS Antiviral treatment for hepatitis C virus (HCV) has high efficacy rates for achieving sustained viral response (SVR) in randomized controlled trials (RCTs) (40-80%); however, it can be lower in community-based practice settings. We wanted to determine the effectiveness of HCV treatment in Veterans Administration (VA) hospitals nationwide. METHODS Using the nationwide VA HCV Clinical Case Registry (CCR), we examined a cohort of veterans who had HCV viremia between 2000 and 2005 and identified patients who received pegylated-interferon (PEG-INF) and ribavirin. The duration of treatment and proportion of patients completing treatment was calculated. The effectiveness of treatment was measured as the proportion of patients who achieved SVR (negative viremia at least 12 weeks after the end of treatment) in the entire cohort, and among patients who initiated and completed treatment. RESULTS We identified 99,166 patients with HCV viremia. Of those, 11.6% received PEG-INF with ribavirin and 6.4% completed treatment. Contraindications were present in 57.2% of the patients that did not receive treatment. SVR was documented in 39.9% and 58.3% of patients who completed treatment; 23.6% and 50.6% of patients who initiated treatment; and 3.9% and 11.2% of the entire HCV cohort for genotype 1 or 4 and 2 or 3, respectively. Overall, only 3.5% of the entire HCV viremic cohort had a documented SVR. CONCLUSIONS Treatment effectiveness for HCV is low. In addition to fixed factors, such as race and virus genotype, the drop in effectiveness is due to low rates of antiviral treatment initiation and treatment completion.
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Delgado JS, Baumfeld Y, Novack V, Monitin S, Jotkowitz A, Etzion O, Fich A. Efficacy of combined pegylated interferon and ribavirin therapy in Jewish patients of Israel suffering from chronic hepatitis C. Hepatol Int 2011; 5:985-990. [PMID: 21553307 DOI: 10.1007/s12072-011-9278-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2010] [Accepted: 04/20/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND PURPOSE The efficacy and safety of pegylated interferon and ribavirin treatment for chronic hepatitis C (CHC) in the Jewish population has not been previously ascertained. The aims of our study were to determine the efficacy of pegylated interferon and ribavirin therapy in an Israeli outpatient practice. METHODS The medical records of 331 consecutive naïve patients with CHC infection treated with pegylated interferon and ribavirin between 2003 and 2010 were reviewed in order to document the virological response to the combination therapy. We used logistic regression to identify predictors for the sustained virological response (SVR). Variable selection in multivariable modeling was based on clinical and statistical significance and performed in a hierarchical fashion. First demographic characteristics, then patient clinical characteristics, viral characteristics, and finally adherence to the therapy were introduced into the model. RESULTS The overall SVR was 57.1% (42.5% in genotype 1, 87.5% in genotype 2, 81.6% in genotype 3, and 100% in genotype 4). SVR was significantly associated with genotype 2 (OR 3.77, 95% CI 1.04-13.60, P = 0.04), genotype 3 (OR 9.72, 95% CI 4.07-23.20, P < 0.001), baseline viral load lower than 400,000 IU/mL (OR 23.1, 95% CI 8.23-64.98, P < 0.001), and adherence to the 80/80/80 rule (OR 36.22, 95% CI 11.14-117.72, P < 0.001). CONCLUSIONS Combined pegylated interferon and ribavirin therapy was of similar or even higher efficacy in the Israeli population as compared to that reported by international trials in Caucasian, Hispanic, and African American populations.
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Affiliation(s)
- Jorge-Shmuel Delgado
- Department of Gastroenterology and Hepatology, Faculty of Health Sciences, The Barzilai Medical Centre, Ben-Gurion University of the Negev, Beersheba, Israel.
| | - Yael Baumfeld
- Faculty of Health Sciences, Clinical Research Centre, Soroka University Medical Centre, Ben-Gurion University of the Negev, Beersheba, Israel
| | - Victor Novack
- Faculty of Health Sciences, Clinical Research Centre, Soroka University Medical Centre, Ben-Gurion University of the Negev, Beersheba, Israel
| | - Shulamit Monitin
- Department of Gastroenterology and Hepatology, Faculty of Health Sciences, Soroka University Medical Centre, Ben-Gurion University of the Negev, Beersheba, Israel
| | - Alan Jotkowitz
- Department of Gastroenterology and Hepatology, Faculty of Health Sciences, Soroka University Medical Centre, Ben-Gurion University of the Negev, Beersheba, Israel
- Department of Internal Medicine, Faculty of Health Sciences, Soroka University Medical Centre, Ben-Gurion University of the Negev, Beersheba, Israel
| | - Ohad Etzion
- Faculty of Health Sciences, Clinical Research Centre, Soroka University Medical Centre, Ben-Gurion University of the Negev, Beersheba, Israel
| | - Alexander Fich
- Faculty of Health Sciences, Clinical Research Centre, Soroka University Medical Centre, Ben-Gurion University of the Negev, Beersheba, Israel
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Innes HA, Hutchinson SJ, Allen S, Bhattacharyya D, Bramley P, Delahooke TES, Dillon JF, Forrest E, Fraser A, Gillespie R, Goldberg DJ, Kennedy N, McDonald S, McLeod A, Mills PR, Morris J, Hayes P. Excess liver-related morbidity of chronic hepatitis C patients, who achieve a sustained viral response, and are discharged from care. Hepatology 2011; 54:1547-58. [PMID: 22045672 DOI: 10.1002/hep.24561] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
UNLABELLED Our objective was to address two shortfalls in the hepatitis C virus (HCV) literature: (1) Few data exist comparing post-treatment liver-related mortality/morbidity in HCV-sustained virologic response (SVR) patients to non-SVR patients and (2) no data exist examining liver-related morbidity among treatment response subgroups,particularly among noncirrhotic SVR patients, a group who in the main are discharged from care without further follow-up. A retrospective cohort of 1,215 previously naïve HCV interferon patients (treated 1996-2007)was derived using HCV clinical databases from nine Scottish clinics. Patients were followed up post-treatment for a mean of 5.3 years. (1) By Cox-regression, liver-related hospital episodes (adjusted hazard ratio [AHR]:0.22; 95% confidence interval [CI]: 0.15-0.34) and liver-related mortality [corrected] (AHR: 0.22; 95% CI: 0.09-0.58)were significantly lower in SVR patients, compared to non-SVR patients. (2) Rates of liver-related hospitalization were elevated among all treatment subgroups compared to the general population: Among noncirrhotic SVR patients, adjusted standardized morbidity ratio (SMBR) up to 5.9 (95% CI: 4.5-8.0); among all SVR patients,SMBR up to 10.5 (95% CI: 8.7-12.9); and among non-SVR patients, SMBR up to 53.2 (95% CI: 49.4-57.2).Considerable elevation was also noted among patients who have spontaneously resolved their HCV infection(a control group used to gauge the extent to which lifestyle factors, and not chronic HCV, can contribute toliver-related morbidity), SMBR up to 26.8 (95% CI: 25.3-28.3). CONCLUSIONS (1) Patients achieving an SVR were more than four times less likely to be hospitalized, or die for a liver-related reason, than non-SVR patients and (2) although discharged, noncirrhotic SVR patients harbor a disproportionate burden of liver-related morbidity; up to six times that of the general population. Further, alarming levels of liver-related morbidity in spontaneous resolvers is an important finding warranting further study..
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Affiliation(s)
- Hamish A Innes
- Department of Mathematics and Statistics, University of Strathclyde, Glasgow, Scotland, United Kingdom.
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Ding CB, Zhang JP, Zhao Y, Peng ZG, Song DQ, Jiang JD. Zebrafish as a potential model organism for drug test against hepatitis C virus. PLoS One 2011; 6:e22921. [PMID: 21857967 PMCID: PMC3152561 DOI: 10.1371/journal.pone.0022921] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2011] [Accepted: 07/01/2011] [Indexed: 01/04/2023] Open
Abstract
Screening and evaluating anti- hepatitis C virus (HCV) drugs in vivo is difficult worldwide, mainly because of the lack of suitable small animal models. We investigate whether zebrafish could be a model organism for HCV replication. To achieve NS5B-dependent replication an HCV sub-replicon was designed and created with two vectors, one with HCV ns5b and fluorescent rfp genes, and the other containing HCV's 5′UTR, core, 3′UTR and fluorescent gfp genes. The vectors containing sub-replicons were co-injected into zebrafish zygotes. The sub-replicon amplified in liver showing a significant expression of HCV core RNA and protein. The sub-replicon amplification caused no abnormality in development and growth of zebrafish larvae, but induced gene expression change similar to that in human hepatocytes. As the amplified core fluorescence in live zebrafish was detectable microscopically, it rendered us an advantage to select those with replicating sub-replicon for drug experiments. Ribavirin and oxymatrine, two known anti-HCV drugs, inhibited sub-replicon amplification in this model showing reduced levels of HCV core RNA and protein. Technically, this method had a good reproducibility and is easy to operate. Thus, zebrafish might be a model organism to host HCV, and this zebrafish/HCV (sub-replicon) system could be an animal model for anti-HCV drug screening and evaluation.
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Affiliation(s)
- Cun-Bao Ding
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- College of Chemical Engineering and Biotechnology, Hebei Polytechnic University, Tangshan, Hebei, People's Republic of China
| | - Jing-Pu Zhang
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- * E-mail: (JDJ); (JPZ)
| | - Ye Zhao
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zong-Gen Peng
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dan-Qing Song
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jian-Dong Jiang
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- * E-mail: (JDJ); (JPZ)
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Impact of depressive symptoms and their treatment on completing antiviral treatment in patients with chronic hepatitis C. J Clin Gastroenterol 2010; 44:e178-85. [PMID: 20495464 DOI: 10.1097/mcg.0b013e3181dc250f] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND/GOALS Interferon-induced depression affects 20% to 40% of patients treated for chronic hepatitis C virus (HCV). The aim of our study was to examine the influence of antidepressant treatment and whether this improves the likelihood of completing therapy. METHODS One hundred randomly selected patients with chronic HCV undergoing antiviral therapy at a single center were identified. Patients were categorized as Group 1 (no depressive symptoms during treatment), Group 2 (depressive symptoms without antidepressant therapy), Group 3 (preexisting or prophylactic antidepressants before therapy), and Group 4 (on-demand antidepressant therapy for depressive symptoms). RESULTS Mean age was 49 years with 72% men. Genotype 1 infection was noted in 65% of patients, and the mean pretreatment HCV RNA level was 1,419,919 IU. Patients without earlier depression receiving on-demand therapy (Group 4) had a significantly higher rate of antiviral treatment completion compared with Group 3 (92% vs. 52%; P=0.01). Patients in groups 1 and 4 with no baseline history of depression had similar treatment completion rates. No significant relationship between the use of antidepressant therapy, SVR or premature cessation of therapy was observed. CONCLUSIONS Preexisting depression was associated with lower antiviral treatment completion rates despite the use of prophylactic antidepressant therapy. In patients without preexisting depression, however, on-demand antidepressant therapy for depressive symptoms was strongly associated with the highest treatment completion rates in the cohort. Antidepressant therapy for new or worsening depressive symptoms independent of baseline depression status did not affect the probability of achieving SVR or stopping treatment prematurely.
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Feuerstadt P, Bunim AL, Garcia H, Karlitz JJ, Massoumi H, Thosani AJ, Pellecchia A, Wolkoff AW, Gaglio PJ, Reinus JF. Effectiveness of hepatitis C treatment with pegylated interferon and ribavirin in urban minority patients. Hepatology 2010; 51:1137-43. [PMID: 20049907 DOI: 10.1002/hep.23429] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Randomized controlled trials of hepatitis C virus (HCV) therapy with pegylated interferon and ribavirin have demonstrated sustained viral response rates (SVRs) of 54%-63% (efficacy). Treatment results in clinical practice (effectiveness) may not be equivalent. The goal of this study was to assess the effectiveness of HCV treatment with pegylated interferon and ribavirin in a treatment-naïve, human immunodeficiency virus (HIV)-negative, United States urban population with many ethnic minority patients. We evaluated 2,370 outpatients for HCV therapy from 2001 to 2006 in the Faculty Practice of the Albert Einstein College of Medicine or the attending-supervised Montefiore Medical Center Liver Clinic. Care was supervised by one experienced physician under conditions of everyday clinical practice, and appropriate ancillary resources were made available to all patients. Two hundred fifty-five patients were treated with a mean age of 50 years (60% male, 40% female; 58% Hispanic, 20% African American, 9% Caucasian, 13% other; 68% genotype 1, the remainder genotypes 2 or 3). Patients had at least one liver biopsy. Intention-to-treat analysis (ITT) showed SVR in 14% of genotype 1 patients and 37% in genotype 2/3 patients (P < 0.001). SVR was significantly higher in faculty practice (27%) than in clinic patients (15%) by intention-to-treat (P = 0.01) but not per-protocol analysis (46% faculty practice, 34% clinic). 3.3% of 1,656 treatment-naïve, HIV antibody-negative individuals ultimately achieved SVR. Current hepatitis C therapies may sometimes be unavailable to, inappropriate for, and ineffective in United States urban patients. Treatment with pegylated interferon and ribavirin was less effective in this population than is implied by multinational phase III controlled trials. New strategies are needed to care for such patients.
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Affiliation(s)
- Paul Feuerstadt
- Division of Gastroenterology, Department of Medicine, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx, NY, USA
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Chen TM, Huang PT, Lin CH, Tsai MH, Lin LF, Liu CC, Ho KS, Tung JN. Feasibility of individualized treatment for hepatitis C patients in the real world. J Gastroenterol Hepatol 2010; 25:61-9. [PMID: 19780879 DOI: 10.1111/j.1440-1746.2009.05946.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND AND AIM Individualized treatment with a combination of peg-interferon and ribavirin for patients with hepatitis C virus (HCV) infection has been validated in randomized controlled clinical trials, but its usefulness in the real world is unknown. The aim of the present study was to assess the feasibility of individualized treatment for HCV patients compared with standard therapy in a real-life clinical setting. METHODS A total of 253 naïve patients with HCV infection who received peg-interferon and ribavirin combination treatment were analyzed and grouped into one of three clinical settings: (i) infection with genotype non-1 (HCV non-1) and treatment for standard 24 weeks (n = 105; none received an abbreviated therapy); (ii) genotype 1 (HCV-1) and standard therapy for either 24 weeks (n = 71) or 48 weeks (n = 21); and (iii) HCV-1 and individualized treatment (n = 56). The individualized therapy used was an abbreviated 24-week treatment for HCV-1 patients who achieved a rapid virological response, otherwise patients received a 48-week course of treatment. Early termination of treatment at week 16 was recommended for non-responders. RESULTS A sustained virological response (SVR) was achieved in 83.8% of patients with HCV non-1 infection. Among the HCV-1-infected patients, 53.5% of patients who underwent standard 24-week treatment, 66.7% of patients who underwent standard 48-week treatment, and 64.3% of patients treated by individualized therapy achieved SVR. Patients infected with HCV-1 and treated by individualized therapy had a similar efficacy response compared with the standard 48-week therapy (adjusted odds ratio [OR] 0.765, 95% confidence interval [CI], 0.220-2.659, P = 0.673). Both individualized therapy (adjusted OR 2.855, 95% CI 1.189-6.855, P = 0.019) or standard 48-week treatment (adjusted OR 3.733, 95% CI 1.073-12.986, P = 0.038) had significantly higher odds of SVR compared with HCV-1 patients treated by standard 24-week course. CONCLUSION Individualized therapy is feasible in the real world, especially for patients with HCV-1 infection.
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Affiliation(s)
- Tsung-Ming Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan.
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Ridruejo E, Adrover R, Cocozzella D, Fernández N, Reggiardo MV. Efficacy, tolerability and safety in the treatment of chronic hepatitis C with combination of PEG-Interferon - Ribavirin in daily practice. Ann Hepatol 2010; 9:46-51. [PMID: 20308722 DOI: 10.1016/s1665-2681(19)31678-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/08/2023]
Abstract
BACKGROUND Efficacy and safety of Pegylated Interferon alfa (PegIFN)-Ribavirin (RBV) for the treatment of chronic hepatitis C (CHC) in routine clinical practice seems to be comparable with results of randomized-controlled trials. AIMS To evaluate the efficacy, tolerability and safety of CHC treatment with PegIFN + RBV in .real world. patients in Argentina and to analyze factors associated with SVR. METHODS Medical records of patients treated according to current guidelines from 2001 to 2008 were reviewed. RESULTS 235 patients were included and 80.8% completed treatment. Discontinuation occurred in 7.6% due to adverse events (AE), and 1.2% dropped-out treatment. Overall SVR was 60.8%. Multivariate analysis demonstrated that being naive (p 0.031) and low basal viral load (p 0.006) were associated with SVR, whereas F3-F4 (p 0.001) and elevated ALT (p 0.023) were associated with non-response. 80% of planned doses completed was associated with 74% SVR (p <0.001). At least one AE was reported in 93.6% of the patients: neutropenia in 27.6%, thrombocytopenia in 15.3%, anemia in 38.7%, psychiatric symptoms in 63.4%, thyroid dysfunction in 10.2%. CONCLUSION Efficacy, tolerability and safety of treatment of CHC in daily practice in Argentina are similar to those reported in randomized controlled trials.
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Affiliation(s)
- Ezequiel Ridruejo
- Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno, CEMIC, Ciudad Autónoma de Buenos Aires, Argentina.
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Borroni G, Andreoletti M, Casiraghi MA, Ceriani R, Guerzoni P, Omazzi B, Terreni N, Salerno F. Effectiveness of pegylated interferon/ribavirin combination in 'real world' patients with chronic hepatitis C virus infection. Aliment Pharmacol Ther 2008; 27:790-7. [PMID: 18298638 DOI: 10.1111/j.1365-2036.2008.03657.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
BACKGROUND Clinical trials have shown that the combination of pegylated interferon/ribavirin induces a sustained virological response in 54-63% of patients with chronic hepatitis C virus infection, but its effectiveness in day-to-day clinical practice is less clear. AIM To verify if the efficacy of pegylated interferon/ribavirin combination in 'real world' patients is comparable to that observed in trials. Methods The medical records of 397 consecutive naïve patients with chronic hepatitis C virus infection treated with pegylated interferon/ribavirin combination in nontertiary hospital settings were reviewed in order to assess the response to anti-viral treatment. RESULTS The sustained virological response rate achieved in this population was similar to that recorded in registration trials (total population: 64%; genotype 1: 46%; genotypes 2-3: 84%). Also, the premature discontinuation rate (15%) was similar to that observed in registration trials, but there were fewer dose reductions in one or both medications (26%). We confirmed the association between adherence and sustained virological response among the patients infected with hepatitis C virus genotype 1 who were treated for > or =80% of the planned duration of treatment. CONCLUSION The effectiveness of pegylated interferon/ribavirin therapy and factors predicting an sustained virological response in everyday clinical practice mirror those reported in randomized-controlled studies.
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Affiliation(s)
- G Borroni
- Unità Organizzativa Alcoldipendenze, ASL Provincia di Milano 1, Abbiategrasso, Milan, Italy.
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Batey RG. Controversies in and challenges to our understanding of hepatitis C. World J Gastroenterol 2007; 13:4168-76. [PMID: 17696244 PMCID: PMC4250614 DOI: 10.3748/wjg.v13.i31.4168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Discovered in 1989, the hepatitis C virus (HCV) continues to cause significant morbidity and mortality world-wide despite a huge research commitment to defining and understanding the virus and the disease it causes. This paper discusses a number of areas where progress in the management of the HCV have not kept pace with the scientific understanding of the HCV. It is suggested that in the fields of HCV prevention and providing access to treatment, practice falls short of what could be achieved. The role of alcohol in the pathogenesis of HCV liver injury is discussed. Discrimination against those with HCV infection and particularly those in prison settings fails to match good clinical practice. The complicated processes of sharing information between specialty groups is also discussed in an attempt to optimise knowledge dissemination in this field.
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Affiliation(s)
- Robert G Batey
- Drug and Alcohol Clinical Services, Hunter New England Area Health Services, Newcastle, New South Wales, Australia.
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