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Van Nuys K, Brookmeyer R, Chou JW, Dreyfus D, Dieterich D, Goldman DP. Broad Hepatitis C Treatment Scenarios Return Substantial Health Gains, But Capacity Is A Concern. Health Aff (Millwood) 2017; 34:1666-74. [PMID: 26438742 DOI: 10.1377/hlthaff.2014.1193] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Treatment of hepatitis C virus, the most common chronic viral infection in the United States, has historically suffered from challenges including serious side effects, low efficacy, and ongoing transmission and reinfection. Recent innovations have produced breakthrough therapies that are effective in more than 90 percent of patients. These treatments could dramatically reduce the virus's prevalence but are costly. To quantify the benefit of these treatments to society, including the value of reduced transmission, we estimated the effects of several hepatitis C treatment strategies on cost and population health. Treating patients at all disease stages could generate $610-$1,221 billion in additional quality-adjusted life-years, plus an additional $139 billion in saved medical expenditures over fifty years, and minimize the disease burden, but up-front treatment costs would exceed $150 billion. An intermediate scenario--treating 5 percent of the infected population annually, regardless of patients' disease stages--would also return substantial benefits and would be much more affordable under current financing schemes.
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Affiliation(s)
- Karen Van Nuys
- Karen Van Nuys is a senior research economist at Precision Health Economics, in Los Angeles, California
| | - Ronald Brookmeyer
- Ronald Brookmeyer is a professor of biostatistics at the University of California, Los Angeles
| | - Jacquelyn W Chou
- Jacquelyn W. Chou is an associate director and research scientist at Precision Health Economics
| | - David Dreyfus
- David Dreyfus is a data scientist at Arete Analytics, in Andover, Massachusetts
| | - Douglas Dieterich
- Douglas Dieterich is a professor of medicine in the Division of Liver Diseases at the Icahn School of Medicine at Mount Sinai, in New York City
| | - Dana P Goldman
- Dana P. Goldman is the Leonard D. Schaeffer Chair and director of the Schaeffer Center for Health Policy and Economics at the University of Southern California, in Los Angeles
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Cheng EY, Saab S, Holt CD, Busuttil RW. Paritaprevir/ritonavir/ombitasvir and dasabuvir for the treatment of chronic hepatitis C virus infection. Expert Opin Pharmacother 2015; 16:2835-48. [DOI: 10.1517/14656566.2015.1114099] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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Lens S, Bonacci M. Coste y efectividad de los nuevos antivirales para la hepatitis C. Aten Primaria 2015; 47:479-81. [PMID: 26433699 PMCID: PMC6983822 DOI: 10.1016/j.aprim.2015.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2015] [Accepted: 06/30/2015] [Indexed: 11/09/2022] Open
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McPhee F, Suzuki Y, Toyota J, Karino Y, Chayama K, Kawakami Y, Yu ML, Ahn SH, Ishikawa H, Bhore R, Zhou N, Hernandez D, Mendez P, Kumada H. High Sustained Virologic Response to Daclatasvir Plus Asunaprevir in Elderly and Cirrhotic Patients with Hepatitis C Virus Genotype 1b Without Baseline NS5A Polymorphisms. Adv Ther 2015; 32:637-649. [PMID: 26155891 PMCID: PMC4522028 DOI: 10.1007/s12325-015-0221-5] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Oral daclatasvir (DCV; pangenotypic NS5A inhibitor) plus asunaprevir (ASV; NS3 protease inhibitor) is approved in Japan and Korea for treatment of chronic hepatitis C virus (HCV) genotype 1. Response to DCV + ASV is affected by DCV resistance-associated polymorphisms (RAPs) in HCV NS5A. The prevalence and influence of these RAPs on 12-week sustained virologic response (SVR12) to DCV + ASV was evaluated in Asian and non-Asian patients. METHODS Data were pooled from 5 national and international studies of patients with HCV genotype 1b (GT-1b) receiving DCV + ASV at their recommended doses. Baseline NS5A RAPs and their effect on SVR12 were assessed overall, in older (≥65 years) patients, patients with cirrhosis, and in patients stratified by baseline HCV RNA or prior treatment experience with interferon-based therapy. RESULTS Baseline NS5A sequences were available from 988 patients (374 Japanese; 125 Korean/Taiwanese; 489 from non-Asian countries), 979 of whom were assessed for SVR12. Pretreatment NS5A-L31F/I/M/V and/or NS5A-Y93H polymorphisms were present in 18% of Japanese and 12-13% of non-Japanese patients; these RAPs reduced SVR12 by 54.9% overall (93.9% [787/838] SVR12 when absent, 39.0% [55/141] SVR12 when present), with comparable reductions observed in Asians and non-Asians and across all categories of treatment experience, age, and cirrhosis. RAP-associated SVR12 rates declined with increasing baseline HCV RNA (SVR12 with RAPs: 64.7% [11/17] at 5-6 log10 IU/mL, 29.8% [14/47] at 7-8 log10). Without baseline RAPs, very high SVR12 rates (92-100%) were observed in older patients and patients with cirrhosis irrespective of national origin, with similarly high rates observed among treatment-naïve and interferon-experienced patients and those with high baseline HCV RNA. CONCLUSIONS Following DCV + ASV treatment, the SVR12 rates in GT-1b patients without baseline NS5A-L31F/I/M/V and/or NS5A-Y93H polymorphisms were very high (approximately 90-100%), irrespective of age, cirrhosis, prior interferon treatment, or baseline HCV RNA. FUNDING Bristol-Myers Squibb.
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Affiliation(s)
- Fiona McPhee
- Bristol-Myers Squibb Research and Development, Wallingford, CT, USA,
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Abstract
In France, 190,306 patients were suffering from chronic hepatitis C in 2012. These patients have a decreased life expectancy and are susceptible to complications associated with chronic hepatitis. Current treatments are poorly tolerated and their effectiveness varies depending on the genotype of the virus. Sofosbuvir, a new class of treatment, has demonstrated in five phase III trials sustained viral response (SVR) rates of over 90% across genotypes, higher than current treatments and has a tolerance profile similar to placebo. The objective was to determine the cost-effectiveness of using sofosbuvir in the treatment of chronic HCV infection. A Markov model was used to compare treatment strategies with and without sofosbuvir. The model simulated the natural history of HCV infection. SVR rates were based on data from clinical trials. Utilities associated with different stages of disease were based on data from the literature. French direct medical costs were used. Price for sofosbuvir was the price used in the early access program for severe fibrosis stages. The incremental cost-effectiveness ratio for sofosbuvir versus current reference treatments was € 16,278/QALY and varied from 40,000 €/QALY for F0 stages to 12,080 €/QALY for F4 stages. The sensitivity analyses carried out confirmed the robustness of this result. Sofosbuvir is a cost-effective treatment option for patients with hepatitis C.
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Affiliation(s)
- H Leleu
- Public health expertiseParis, France
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Hu CC, Lin CL, Chang LC, Chien CH, Chen LW, Liu CJ, Chien RN. Interleukin-28B gene non-TT allele strongly predicts treatment failure for genotype 1 infected chronic hepatitis C patients with advanced fibrosis: a case control study. BMC Infect Dis 2015; 15:156. [PMID: 25888020 PMCID: PMC4377185 DOI: 10.1186/s12879-015-0888-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2014] [Accepted: 03/12/2015] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND The role of single nucleotide polymorphisms (SNPs) of interleukin (IL)-28B in predicting therapeutic response of pegylated interferon (peg-IFN) plus ribavirin (PR) for genotype 1 infected chronic hepatitis C patients with advanced fibrosis (AF) is limited. The aim of this study is to assess its role in predicting sustained virologic responses (SVR) to treatment. METHODS Forty-two patients with biopsy proven hepatitis C virus (HCV) related AF (group A; Ishak fibrosis score, ≥4) and 126 sex- and HCV genotype-matched patients without AF (group B; Ishak fibrosis score, ≤3) were recruited into study. All patients received PR therapy for 24 weeks. Baseline and on-treatment clinical, virological and host factors were evaluated for treatment efficacy. RESULTS The SVR rate was significantly lower in group A than group B patients with genotype 1 infection (24% vs. 53.3%; p=0.011). However, it was similar in those with genotype non-1 infection (76.5% vs. 76.5%; p=1.0). IL-28B rs8099917 genotype TT is the strongest predictor for SVR in genotype 1 infection. Patients who had TT genotype and achieved RVR in group A had similar SVR rates with those in group B (44.4% vs. 53.3%; p=0.614). One third of patients in group A developed hematological adverse effects and had required modified doses during antiviral therapy. CONCLUSIONS In HCV genotype 1 infected AF receiving 24 weeks of PR treatment, patients with IL28B rs8099917 genotype TT, achieving RVR had similar SVR rate with those without AF. In contrast, patients with IL-28B rs8099917 non-TT genotype without achieving RVR are suggested to stop therapy.
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Affiliation(s)
- Ching-Chih Hu
- Liver Research Unit, Chang Gung Memorial Hospital, 222 Mai-Chin Road, Keelung, 20401, Taiwan.
| | - Chih-Lang Lin
- Liver Research Unit, Chang Gung Memorial Hospital, 222 Mai-Chin Road, Keelung, 20401, Taiwan.
| | - Liang-Che Chang
- Department of Pathology, Chang Gung Memorial Hospital, 222 Mai-Chin Road, Keelung, 20401, Taiwan.
| | - Cheng-Hung Chien
- Liver Research Unit, Chang Gung Memorial Hospital, 222 Mai-Chin Road, Keelung, 20401, Taiwan.
| | - Li-Wei Chen
- Liver Research Unit, Chang Gung Memorial Hospital, 222 Mai-Chin Road, Keelung, 20401, Taiwan.
| | - Ching-Jung Liu
- Liver Research Unit, Chang Gung Memorial Hospital, 222 Mai-Chin Road, Keelung, 20401, Taiwan.
| | - Rong-Nan Chien
- Liver Research Unit, Chang Gung Memorial Hospital, 222 Mai-Chin Road, Keelung, 20401, Taiwan.
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Chandra PK, Gunduz F, Hazari S, Kurt R, Panigrahi R, Poat B, Bruce D, Cohen AJ, Behorquez HE, Carmody I, Loss G, Balart LA, Wu T, Dash S. Impaired expression of type I and type II interferon receptors in HCV-associated chronic liver disease and liver cirrhosis. PLoS One 2014; 9:e108616. [PMID: 25265476 PMCID: PMC4180933 DOI: 10.1371/journal.pone.0108616] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2014] [Accepted: 08/22/2014] [Indexed: 12/12/2022] Open
Abstract
PURPOSE Chronic Hepatitis C Virus (HCV)-infected patients with liver cirrhosis (LC) respond poorly to interferon-alpha (IFN-α) and ribavirin (RBV) combination therapy, but the reason for this is unclear. We previously reported that HCV-infection induces endoplasmic reticulum (ER) stress and autophagy response that selectively down regulates the type I IFN-α receptor-1 (IFNAR1) and RBV transporters (CNT1 and ENT1), leading to IFN-α/RBV resistance. The goal of this study is to verify whether an increase in ER stress and autophagy response is also associated with the reduced expression of IFNAR1 and RBV transporters in chronic HCV-infected patients. METHODS Primary human hepatocytes (PHH) were infected with cell culture grown HCV particles (JFH-ΔV3-Rluc). HCV replication was confirmed by the detection of viral RNA by RT-qPCR and HCV-core protein by Western blotting. The ER stress and autophagy response and expression of IFN receptors and RBV transporters in HCV infected PHH and liver tissues derived from patients were measured by Western blotting. RESULT HCV infection of PHH showed impaired expression of IFNAR1, IFNγR1 (Type II IFN receptor) and RBV transporters but not IL10Rβ (Type III IFN-λ receptor). ER stress markers (BiP, IRE1α and peIF2α) and autophagy response (LC3II, Beclin 1 and ATG5) were induced in HCV infected chronic liver disease (CLD) and LC patients. Liver biopsies (CLD) show a 50% reduced expression of IFNAR1 and RBV transporters. Furthermore, the expression of IFNAR1 and RBV transporters was impaired in almost all LC patients. CONCLUSION HCV infection induces ER stress and autophagy response in infected PHH and chronically infected liver tissues. The expression of IFNAR1, IFNγR1 and RBV transporters were significantly impaired in CLD and cirrhotic livers. Our study provides a potential explanation for the reduced response rate of IFN-α and RBV combination therapy in HCV infected patients with liver cirrhosis.
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Affiliation(s)
- Partha K. Chandra
- Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana, United States of America
| | - Feyza Gunduz
- Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana, United States of America
| | - Sidhartha Hazari
- Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana, United States of America
| | - Ramazan Kurt
- Department of Medicine, Gastroenterology and Hepatology, Tulane University Health Sciences Center, New Orleans, Louisiana, United States of America
| | - Rajesh Panigrahi
- Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana, United States of America
| | - Bret Poat
- Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana, United States of America
| | - David Bruce
- Transplant Surgery Section, Ochsner Medical Center, New Orleans, Louisiana, United States of America
| | - Ari J. Cohen
- Transplant Surgery Section, Ochsner Medical Center, New Orleans, Louisiana, United States of America
| | - Humberto E. Behorquez
- Transplant Surgery Section, Ochsner Medical Center, New Orleans, Louisiana, United States of America
| | - Ian Carmody
- Transplant Surgery Section, Ochsner Medical Center, New Orleans, Louisiana, United States of America
| | - George Loss
- Transplant Surgery Section, Ochsner Medical Center, New Orleans, Louisiana, United States of America
| | - Luis A. Balart
- Department of Medicine, Gastroenterology and Hepatology, Tulane University Health Sciences Center, New Orleans, Louisiana, United States of America
| | - Tong Wu
- Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana, United States of America
| | - Srikanta Dash
- Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana, United States of America
- Department of Medicine, Gastroenterology and Hepatology, Tulane University Health Sciences Center, New Orleans, Louisiana, United States of America
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Shakado S, Sakisaka S, Okanoue T, Chayama K, Izumi N, Toyoda J, Tanaka E, Ido A, Takehara T, Yoshioka K, Hiasa Y, Nomura H, Seike M, Ueno Y, Kumada H. Interleukin 28B polymorphism predicts interferon plus ribavirin treatment outcome in patients with hepatitis C virus-related liver cirrhosis: A multicenter retrospective study in Japan. Hepatol Res 2014; 44:983-992. [PMID: 24400682 DOI: 10.1111/hepr.12280] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Revised: 11/15/2013] [Accepted: 11/17/2013] [Indexed: 12/22/2022]
Abstract
AIM This study evaluated the efficacy of interferon plus ribavirin and examined whether interleukin 28B (IL28B) polymorphism influenced treatment outcome in Japanese patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). METHODS Fourteen collaborating centers provided details of 261 patients with HCV-related LC undergoing treatment with interferon plus ribavirin. Univariate and multivariate analyses were used to establish which factors predicted treatment outcome. RESULTS Eighty-four patients (32.2%) achieved a sustained virological response (SVR). SVR rates were 21.6% (41/190) in patients with HCV genotype 1 with high viral load (G1H) and 60.6% (43/71) in patients with non-G1H. In patients with non-G1H, treatment outcome was effective irrespective of IL28B polymorphism. In those with G1H, SVR was achieved in 27.1% of patients with the IL28B rs8099917 TT allele compared with 8.8% of those with the TG/GG alleles (P = 0.004). In patients with G1H having TT allele, treatments longer than 48 weeks achieved significantly higher SVR rates than treatments less than 48 weeks (34.6% vs 16.4%, P = 0.042). In patients with G1H having TG/GG alleles, treatments longer than 72 weeks achieved significantly higher SVR rates than treatments less than 72 weeks (37.5% vs 4.1%, P = 0.010). CONCLUSION Interferon plus ribavirin treatment in Japanese patients with non-G1H HCV-related LC was more effective than those with G1H and not influenced by IL28B polymorphism. In those with G1H, IL28B polymorphism may predict SVR and guide treatment duration: SVR rates were higher in those with the TT allele treated for more than 48 weeks and those with the TG/GG alleles treated for more than 72 weeks.
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Affiliation(s)
- Satoshi Shakado
- Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan; Division of Advanced Clinical Research for Viral Hepatitis and Liver Cancer, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
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Zhou H, Luo H, Xiao S, Wang H, Gong G. Predictors for dose reduction of antiviral therapy in older patients infected with hepatitis C virus: a meta-regression analysis. Eur J Clin Microbiol Infect Dis 2013; 33:491-8. [PMID: 24193376 DOI: 10.1007/s10096-013-1992-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2013] [Accepted: 09/30/2013] [Indexed: 01/19/2023]
Abstract
Treatment-related adverse events (AE) were more frequent in older patients treated by pegylated interferon (PEG-IFN) plus ribavirin (RBV) for chronic hepatitis C (CHC), and most of them required dose reduction. A meta-regression analysis was conducted to explore the possible reasons for this occurrence. We searched MEDLINE, EMBASE, and Web of Science through May 2013, for clinical trials examining the safety of PEG-IFN plus RBV in elderly patients with CHC. Data were extracted for host, viral, and outcome information. Single-arm meta-analysis was performed to evaluate AE. Meta-regression analysis was conducted to explore predictors for dose reduction secondary to AE. Eighteen observational studies met the inclusion criteria. The overall incidences of AE were 61.3%. Dose reductions due to AE were 54.2%. In patients with genotype 1, the rate of sustained virological response (SVR) was 36.9%. In patients with genotypes 2 or 3, the rate of SVR was 72.8%. Patients with more dose reduction due to AE have a tendency toward a lower likelihood of obtaining SVR (coefficient:-0.529), especially for genotype 1 patients. Host factors (male gender, coefficient 4.403; higher body weight, coefficient 0.140; and advanced fibrosis stage, coefficient 1.582) and viral factors (HCV genotype 1, coefficient 2.279) have a significant impact on dose reduction due to AE. Some host and viral factors affected dose reduction due to AE. Increasing rates of fibrosis with age may play a role as a mechanism affecting dose reduction secondary to AE and SVR in different age groups.
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Affiliation(s)
- H Zhou
- Department of Infectious Diseases, the Second Xiangya Hospital, Central South University, 139 Renming Middle Road, Changsha, Hunan Province, 410011, China
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Brjalin V, Salupere R, Tallo T, Kuznetsova T, Priimägi L, Tefanova V. Efficacy of peginterferon alpha-2A and ribavirin combination therapy in treatment-naive Estonian patients with chronic hepatitis C. Cent Eur J Public Health 2012; 20:150-5. [PMID: 22966742 DOI: 10.21101/cejph.a3706] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
AIM The aim of the study was to assess the efficacy of pegylated interferon (Peg-IFN) alpha-2a and ribavirin (RBV) combination therapy in treatment-naive patients with chronic hepatitis C in Estonia. METHODS Out of 121 outpatients with chronic hepatitis C (73 males, 48 females, aged 19-63) enrolled in the study, 76 were infected with HCV genotype 1b and 45 with genotype 3a. At baseline, the viral load in 75.2% of patients was higher than 600,000 IU/mL. Histologically, 88.4% of patients had fibrosis score F0-2. Patients received 180 microg of Peg-IFN alpha-2a weekly plus daily ribavirin 1,000 or 1,200 mg, depending on body weight, in HCV genotype 1b, or 800 mg/day in genotype 3a infection. RESULTS The overall sustained virologic response (SVR) rate in our study was 60.3%, being statistically lower for patients with HCV genotype 1b as compared to patients with genotype 3a (46.1% vs. 84.4%, p < 0.05). The non-response and relapse rates were significantly higher in patients infected with HCV genotype 1b compared with patients infected with genotype 3a (19.7% vs. 2.2%, p = 0.01; and 17.1% vs. 4.4%, p = 0.04; respectively). The SVR rate was higher in patients younger than 40 years compared with older patients (76.4% vs. 47.0%, p < 0.01), regardless of the genotype. Thirteen patients infected with HCV genotype 1b required dose reduction of PegIFN and/or RBV because of adverse side effects. Nine of them achieved SVR. CONCLUSION HCV genotype and age younger than 40 years predetermined SVR rate in treatment-naive Estonian patients with chronic hepatitis C treated with Peg-IFN alpha-2a plus ribavirin.
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Affiliation(s)
- Vadim Brjalin
- Department of Intemal Medicine, West-Tallinn Central Hospital, Tallinn, Estonia.
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Harris HE, Costella A, Amirthalingam G, Alexander G, Ramsay MEB, Andrews N. Improved hepatitis C treatment response in younger patients: findings from the UK HCV National Register cohort study. Epidemiol Infect 2012; 140:1830-7. [PMID: 22124380 PMCID: PMC3443967 DOI: 10.1017/s0950268811002317] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/26/2011] [Indexed: 11/06/2022] Open
Abstract
In a cohort of 272 treatment-naive individuals with chronic hepatitis C infection acquired on a known date who were enrolled in the UK HCV National Register, a progressive improvement in response to treatment was found with the evolution of antiviral therapies from 20% (25/122) for interferon monotherapy to 63% (55/88) for pegylated interferon+ribavirin therapy. Multivariable analysis results showed increasing age to be associated with poorer response to therapy [odds ratio (OR) 0·84, 95% confidence interval (CI) 0·72-0·99, P=0·03] whereas time since infection was not associated with response (OR 0·93, 95% CI 0·44-1·98, P=0·85). Other factors significantly associated with a positive response were non-type 1 genotype (P<0·0001) and combination therapies (P<0·0001). During the first two decades of chronic HCV infection, treatment at a younger age was found to be more influential in achieving a sustained viral response than treating earlier in the course of infection.
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Affiliation(s)
- H E Harris
- Immunisation, Hepatitis and Blood Safety Department, Health Protection Services Colindale, Health Protection Agency, 61 Colindale Ave., London, UK.
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Tamai H, Shingaki N, Shiraki T, Tukuda H, Mori Y, Moribata K, Enomoto S, Deguchi H, Ueda K, Inoue I, Maekita T, Iguchi M, Yanaoka K, Oka M, Ichinose M. Prediction of sustained response to low-dose pegylated interferon alpha-2b plus ribavirin in patients with genotype 1b and high hepatitis C virus level using viral reduction within 2 weeks after therapy initiation. Hepatol Res 2011; 41:1137-44. [PMID: 21951330 DOI: 10.1111/j.1872-034x.2011.00879.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
AIM Continuation of pegylated interferon (PEG-IFN) plus ribavirin at the recommended dose is difficult in elderly patients and/or patients with cytopenia or complications. Whether the therapeutic efficacy of low-dose PEG-IFN plus ribavirin therapy could be predicted based on virological response within 2 weeks of therapy initiation was evaluated. METHODS A total of 106 patients with a high viral load of genotype-1b hepatitis C virus (HCV) underwent low-dose PEG-IFN plus ribavirin therapy. PEG-IFN alpha 2b (0.75 µg/kg per week) and ribavirin (600-800 mg/day) were administered for 48 weeks. RESULTS Sustained virological response (SVR) was achieved in 37%, and treatment was discontinued in 9%. On univariate analysis of SVR-contributing factors, significant differences were noted in the white blood cell count, platelet count, fibrosis markers, and viral reduction within 2 weeks from therapy initiation. On multivariate analysis, the platelet count and the reduction in the HCV core antigen level at week 2 were independent factors. The positive predictive value (PPV) and the negative predictive value (NPV) for SVR based on a 1-log or greater HCV-RNA level reduction at week 2 were 65% and 90%, respectively, and those based on HCV core antigen level at week 2 were 64% and 97%, respectively. PPV and NPV based on a 2-log or greater reduction of the RNA level were 86% and 67%, respectively, and those based on the core antigen level were 93% and 69%, respectively. CONCLUSION Evaluation of viral reduction at week 2 after therapy initiation is useful for predicting SVR to low-dose PEG-IFN plus ribavirin therapy.
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Affiliation(s)
- Hideyuki Tamai
- Second Department of Internal Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama city, Wakayama 641-0012, Japan
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Reiberger T, Rutter K, Ferlitsch A, Payer BA, Hofer H, Beinhardt S, Kundi M, Ferenci P, Gangl A, Trauner M, Peck-Radosavljevic M. Portal pressure predicts outcome and safety of antiviral therapy in cirrhotic patients with hepatitis C virus infection. Clin Gastroenterol Hepatol 2011; 9:602-8.e1. [PMID: 21397726 DOI: 10.1016/j.cgh.2011.03.002] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2010] [Revised: 02/19/2011] [Accepted: 03/02/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS There are limited data on the efficacy and safety of antiviral therapy in patients with hepatitis C virus (HCV)-related cirrhosis, particularly on the impact of portal hypertension. METHODS We assessed hepatovenous pressure gradient (HVPG), liver stiffness (transient elastography), and interleukin (IL)-28B polymorphisms (rs12979860) in 90 cirrhotic patients with HCV infection (82% genotype 1 or 4) before antiviral therapy with pegylated interferon and ribavirin. Efficacy and safety were evaluated. RESULTS Rates of sustained virologic response were significantly lower among patients with clinically significant portal hypertension (CSPH; HVPG ≥ 10 mm Hg; n = 50) than among patients without CSPH (HVPG <10 mm Hg; n = 40): 14% vs 51% (P = .0007). Seventy-nine percent and 83% of patients with CSPH and without CSPH, respectively, received more than 80% of planned dose (P = .647). The predictive value of HVPG (area under the curve [AUC], 0.743) was greater than that of liver stiffness (AUC, 0.647) or of baseline HCV RNA levels (AUC, 0.620). The IL-28B polymorphism was not associated significantly with a sustained virologic response. Multivariate analysis revealed that HVPG (odds ratio [OR], 14.3; P = .009), baseline HCV RNA levels (OR, 5.3; P = .019), and HCV genotype (OR, 6.5; P = .046) were independent risk factors for treatment failure. A trend toward higher incidence of anemia and neutropenia was observed for patients with CSPH. The incidence and grade of thrombocytopenia were significantly higher among patients with than without CSPH (94% vs 75%; P = .006). CONCLUSIONS HVPG is an independent predictor of response to antiviral therapy, with better predictive value than liver stiffness, baseline HCV RNA levels, HCV genotype, or IL-28B polymorphism. The incidence and grade of thrombocytopenia during antiviral therapy are higher among patients with CSPH. In evaluating cirrhotic HCV patients for antiviral treatment, measurement of HVPG should be considered.
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Affiliation(s)
- Thomas Reiberger
- Department of Internal Medicine III, Division of Gastroenterology & Hepatology, Medical University of Vienna, Vienna, Austria
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14
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Kobayashi M, Suzuki F, Akuta N, Suzuki Y, Sezaki H, Yatsuji H, Kawamura Y, Hosaka T, Kobayashi M, Arase Y, Ikeda K, Mineta R, Iwasaki S, Watahiki S, Miyakawa Y, Kumada H. Development of hepatocellular carcinoma in elderly patients with chronic hepatitis C with or without elevated aspartate and alanine aminotransferase levels. Scand J Gastroenterol 2010; 44:975-83. [PMID: 19521923 DOI: 10.1080/00365520802588125] [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: 02/06/2023]
Abstract
OBJECTIVE Hepatocellular carcinoma (HCC) in the elderly infected with hepatitis C virus (HCV) is expected to increase globally within the next two decades. The purpose of the study was to define the natural history of elderly patients with chronic hepatitis C needs in order to prevent HCC from arising in these patients. MATERIAL AND METHODS Treatment-naive patients aged >or=65 years with platelet counts >120 x 10(3)/mm(3) were classified as 120 with aspartate and alanine aminotransferase (ASAT and ALAT) levels <or=40 IU/l (group A) and 212 with either or both levels >or=41 (group B) and followed-up for 3 years or longer without antiviral treatment. RESULTS Cirrhosis and HCC developed more frequently in group B than in group A (p<0.001 for both). In particular, of the patients aged 65-69 years at entry, cirrhosis and HCC developed more frequently in group B than in group A (p<0.001 and p=0.001, respectively). Liver-related causes of death were more common in group B than in group A (20/34 (59%) versus 1/9 (11%), p=0.021). HCC developed more frequently in men than in women (p=0.033). CONCLUSIONS In elderly patients with chronic hepatitis C, cirrhosis and HCC develop more frequently in those with elevated transaminase levels than in those without elevated transaminase levels. Therefore, transaminase levels need to be suppressed below <or=40 IU/l, using antiviral treatments or other agents, in order to prevent cirrhosis and HCC arising in these patients. In view of rare liver-related deaths, aggressive antiviral treatment would not be necessary in the elderly with chronic hepatitis C who have normal transaminase levels.
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Affiliation(s)
- Mariko Kobayashi
- Research Institute for Hepatology, Toranomon Hospital, Tokyo, Japan.
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15
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Chen L, Borozan I, Sun J, Guindi M, Fischer S, Feld J, Anand N, Heathcote J, Edwards AM, McGilvray ID. Cell-type specific gene expression signature in liver underlies response to interferon therapy in chronic hepatitis C infection. Gastroenterology 2010; 138:1123-33.e1-3. [PMID: 19900446 DOI: 10.1053/j.gastro.2009.10.046] [Citation(s) in RCA: 87] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2009] [Revised: 10/01/2009] [Accepted: 10/29/2009] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Chronic hepatitis C virus (CHC) infection is treated with interferon/ribavirin, but only a subset of patients respond. Treatment nonresponders have marked pretreatment up-regulation of a subset of interferon stimulated genes (ISGs) in their livers, including ISG15. We here study how the nonresponder gene expression phenotype is influenced by clinical factors and uncover the cellular basis of the phenotype through ISG15 protein expression. METHODS Seventy-eight CHC patients undergoing treatment were classified by clinical (gender, viral genotype, viral load, treatment outcome) and histologic (inflammation, fibrosis) factors and subjected to gene expression profiling on their pretreatment liver biopsies. An analysis of variance model was used to study the influence of individual factors on gene expression. ISG15 immunohistochemistry was performed on a subset of 31 liver biopsy specimens. RESULTS One hundred twenty-three genes were differentially expressed in the 78 CHC livers when compared with 20 normal livers (P < .001; fold change, > or =1.5-fold). Of genes influenced by a single factor, genotype (1 vs 2/3) influenced more genes (17) than any other variable; when treatment outcome was included in the analysis, this became the predominant influence (24 genes), and the effect of genotype was diminished. Treatment response was linked to cell-specific activation patterns: ISG15 protein up-regulation was more pronounced in hepatocytes in treatment nonresponders but in Kuppfer cells in responders. CONCLUSIONS Genotype is a surrogate marker for the nonresponder phenotype. This phenotype manifests as differential gene expression and is driven by activation of different cell types: hepatocytes in treatment nonresponders and macrophages in treatment responders.
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Affiliation(s)
- Limin Chen
- Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada
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16
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Meier V, Ramadori G. Hepatitis C virus virology and new treatment targets. Expert Rev Anti Infect Ther 2009; 7:329-50. [PMID: 19344246 DOI: 10.1586/eri.09.12] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Hepatitis C virus (HCV) infection is the leading cause of chronic liver disease. An estimated 130 million people worldwide are persistently infected with HCV. Almost half of patients who have chronic HCV infection cannot be cured with the standard treatment consisting of pegylated IFN-alpha and ribavirin. For those patients who do not respond to this standard antiviral therapy, there is currently no approved treatment option available. Recent progress in structure determination of HCV proteins and development of a subgenomic replicon system enables the development of a specifically targeted antiviral therapy for hepatitis C. Many HCV-specific compounds are now under investigation in preclinical and clinical trials.
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Affiliation(s)
- Volker Meier
- Universitätsmedizin Göttingen, Abteilung für Gastroenterologie und Endokrinologie, Göttingen, Germany
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17
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Syed E, Rahbin N, Weiland O, Carlsson T, Oksanen A, Birk M, Davidsdottir L, Hagen K, Hultcrantz R, Aleman S. Pegylated interferon and ribavirin combination therapy for chronic hepatitis C virus infection in patients with Child-Pugh Class A liver cirrhosis. Scand J Gastroenterol 2009; 43:1378-86. [PMID: 18615358 DOI: 10.1080/00365520802245395] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Pegylated interferon (peg-IFN) and ribavirin (RBV) treatment is less effective in patients with hepatitis C virus (HCV) and liver cirrhosis than in non-cirrhotic patients. Many patients with advanced liver disease have been excluded from the pivotal randomized controlled studies. The aim of this study was to investigate the efficacy and tolerability of combination therapy in unselected patients with Child-Pugh Class A liver cirrhosis at a Swedish university clinic. MATERIAL AND METHODS The virologic response and adverse events were retrospectively analyzed in 104 patients with HCV-associated Child-Pugh Class A liver cirrhosis who had been treated with peg-IFN and RBV. RESULTS Overall sustained virologic response (SVR) was achieved in 13% genotype 1-, 60% genotype 2-, and 31% genotype 3-infected patients. In treatment-naive patients, the corresponding rates were 13%, 82%, and 38%, respectively. In 46% of patients, treatment was discontinued prematurely owing to lack of virologic response in the majority. CONCLUSIONS SVR rates found in our study, in particular for genotype 1 patients (13%), were lower than those generally found in randomized controlled studies. For cirrhotic patients, new treatment alternatives are urgently needed to improve treatment outcome.
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Affiliation(s)
- Eliya Syed
- Department of Gastroenterology and Hepatology, Karolinska University Hospital, Sweden
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18
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Cacopardo B, Nunnari G, Benanti F, Cappellani A, Onorante A, Caltabiano E, Russo R. Leukocyte interferon alpha early retreatment for Child A HCV genotype 1b-infected cirrhotics intolerant to pegylated interferons. Infection 2008; 37:210-5. [PMID: 19139808 DOI: 10.1007/s15010-008-8164-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2008] [Accepted: 08/19/2008] [Indexed: 11/26/2022]
Abstract
BACKGROUND AND AIM The pegylated interferon (PEG-IFN)/ribavirin combination has been shown to be effective for hepatitis C virus (HCV)-related compensated cirrhosis, but it frequently causes adverse events, leading to premature termination. In this open study we evaluated the safety and efficacy of early retreatment with leukocyte IFN-alpha in Child A HCV genotype 1b-infected cirrhotics intolerant to PEG-IFNs. PATIENTS AND METHODS 61 patients were treated with PEG-IFN (either alpha-2b 1.2-1.5 lg/kg weekly or alpha-2a 180 lg/weekly) plus ribavirin (1,000 mg/day) for 48 weeks. During the first 6 months, patients who discontinued treatment because of side effects were retreated with leukocyte IFN-alpha (6 MU/three times weekly) plus ribavirin (1,000 mg/day) for 48 weeks after a 1-month wash-out. The primary end points were safety and efficacy in terms of sustained virological response (SVR). RESULTS At intention-to-treat analysis of the 61 patients receiving PEG-IFNs plus ribavirin revealed that 18 (29.5%) obtained a SVR. 16 patients (26.2%) prematurely discontinued treatment and were retreated with leukocyte IFN-alpha plus ribavirin. The switch was well tolerated, and all but one patient completed the treatment period. As a result of the switch, 4 of these 16 (25%) patients also obtained a SVR. Thus, the overall SVR rate of this study was 22/61 (36.1%). CONCLUSIONS These results suggest that an early retreatment with leukocyte IFN-alpha may be a safe and valid therapeutic option among difficult-to-treat HCV cirrhotic patients who cannot tolerate PEG-IFNs.
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Affiliation(s)
- B Cacopardo
- Department of Internal Medicine and Medical Specialties, Institute of Infectious Diseases, University of Catania, Via Passo Gravina 187, 90157, Catania, Italy.
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Abstract
Chronic hepatitis C (HCV) infection remains a major health problem worldwide. The current standard of care is a combination of pegylated interferon-alpha and ribavirin. Considering the length of antiviral therapy, as well as its side effects and costs, accurate prediction of treatment response prior to initiation of treatment is critical. In addition to viral, demographic and environmental factors, host genetic diversity is believed to contribute to the spectrum of clinical outcomes of chronic HCV. The development of high-throughput technologies provides opportunities to define patterns of gene expression that are associated with certain disease outcomes and/or response to therapy. This article reviews genomics-based predictors of pre-treatment response to antiviral therapy.
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20
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Mendes LSC, Nita ME, Ono-Nita SK, Mello ES, Silva LCD, Alves VAF, Carrilho FJ. Prognostic factors for progression of liver structural lesions in chronic hepatitis C patients. World J Gastroenterol 2008; 14:2522-8. [PMID: 18442199 PMCID: PMC2708363 DOI: 10.3748/wjg.14.2522] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the epidemiological, clinical, laboratory and histological variables capable of predicting the progression of hepatic structural disturbances in chronic hepatitis C patients during the time interval between two liver biopsies.
METHODS: Clinical charts of 112 chronic hepatitis C patients were retrospectively analyzed, whereas liver biopsies were revised. Immunohistochemical detection of interferon receptor was based on the Envision-Peroxidase System.
RESULTS: In the multivariate analysis, the variables in the age at first biopsy, ALT levels, presence of lymphoid aggregates and siderosis were the determinants of the best model for predicting the severity of the disease. The direct progression rate of hepatic structural lesions was significantly higher in untreated patients, intermediate in treated non-responders and lower in treated responders to antiviral therapy (non-treated vs responders, 0.22 ± 0.50 vs -0.15 ± 0.46, P = 0.0053). Immuno-expression of interferon receptor is not a relevant factor.
CONCLUSION: The best predictors of the progression of fibrosis are age at the first liver biopsy, extent of ALT elevation, inflammation at liver histology and hepatic siderosis. Antiviral treatment is effective in preventing the progression of liver structural lesions in chronic hepatitis C patients.
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21
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Jensen GS, Trotter JF. Treatment of chronic HCV in advanced liver disease: unmet challenges, reason for optimism. J Hepatol 2007; 47:441-3. [PMID: 17692987 DOI: 10.1016/j.jhep.2007.07.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
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Di Marco V, Almasio PL, Ferraro D, Calvaruso V, Alaimo G, Peralta S, Di Stefano R, Craxì A. Peg-interferon alone or combined with ribavirin in HCV cirrhosis with portal hypertension: a randomized controlled trial. J Hepatol 2007; 47:484-91. [PMID: 17692985 DOI: 10.1016/j.jhep.2007.04.020] [Citation(s) in RCA: 81] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2006] [Revised: 04/10/2007] [Accepted: 04/26/2007] [Indexed: 12/12/2022]
Abstract
BACKGROUND/AIMS Risks and benefits of antiviral therapy in HCV cirrhosis with portal hypertension are poorly known. METHODS We performed a randomized controlled trial in 102 HCV patients with compensated cirrhosis and portal hypertension: 51 received 1 microg/kg/week of Pegylated-interferon alpha-2b and 51 Pegylated-interferon plus 800 mg/day of ribavirin up to 52 weeks. RESULTS By intention-to-treat analysis, five patients on monotherapy and eleven on combination therapy achieved a sustained virological response (9.8% vs. 21.6%, p=0.06). The response was more frequent for genotypes 2 or 3 than genotype 1 (66.6% vs. 11.3%, p=0.001). Genotype 1, who had low viral load at start of therapy, were HCV-RNA negative at 4 weeks, and were adherent to the scheduled therapy had a higher probability of sustained virological response. Patients with sustained virological response had less disease events compared to nonresponders (6.2% vs. 38.3%, p=0.03 by log rank test) during follow-up. CONCLUSIONS In HCV cirrhosis with portal hypertension Peg-interferon plus ribavirin is a feasible treatment. Although the rate of viral eradication is modest, tailoring by genotype and early viral response allows to keep patients on treatment who are more likely to have viral eradication. Patients with viral eradication have fewer disease complications during follow-up.
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Affiliation(s)
- Vito Di Marco
- Cattedra di Gastroenterologia and Unità Operativa Complessa di Gastroenterologia ed Epatologia, Di.Bi.M.I.S, Piazza delle Cliniche 2, 90127 Palermo, Italy.
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23
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Abstract
Acute and chronic hepatitis C virus (HCV) infection remains a serious health problem worldwide, however, there has been advancement in the treatment of HCV infection due to standard treatment using pegylated interferon and ribavirin. The literature indicates that therapy for HCV is becoming more individualized. In addition to considering genotype and viral RNA levels before treatment, achievement of an early virologic response (EVR) and a rapid virologic response (RVR) is now possible during therapy. Moreover, problem patients, such as non-responders, relapsers, HIV or HBV co-infected patients, patients with liver cirrhosis, and pre- or post-liver transplantation patients are an increasing fraction of the patients requiring treatment. This article reviews the literature regarding standard treatments and problem patients with acute and chronic HCV infection. It also includes discussion on contraindications and side effects of treatment with interferon and ribavirin, as well as new drug development.
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Affiliation(s)
- Kilian Weigand
- University of Heidelberg, Department of Gastroenterology, Im Neuenheimer Feld 410, Hei-delberg D-69120, Germany
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24
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Fartoux L, Degos F, Trépo C, Goria O, Calès P, Tran A, Buffet C, Poynard T, Capron D, Raabe JJ, Roulot D, Naveau S, Grange JD, Poupon RE, Poupon R, Serfaty L. Effect of prolonged interferon therapy on the outcome of hepatitis C virus-related cirrhosis: a randomized trial. Clin Gastroenterol Hepatol 2007; 5:502-7. [PMID: 17261383 DOI: 10.1016/j.cgh.2006.10.016] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The impact of interferon (IFN) treatment on the occurrence of complications related to hepatitis C virus (HCV)-related cirrhosis is debated because the majority of studies are retrospective. We designed a randomized controlled trial comparing the efficacy of prolonged IFN alfa-2a treatment vs nontreatment on complication-free survival in patients with compensated HCV cirrhosis. METHODS A total of 102 patients (mean age, 60.5 +/- 9.5 y; male/female ratio, .82) with biopsy examination-proven HCV cirrhosis, Child-Pugh score A, who were hepatocellular carcinoma (HCC) free, and had at least 1 risk factor of complications were randomized to receive IFN or no therapy for 24 months. RESULTS During the follow-up evaluation, the complication rate was 24.5%: HCC occurred in 12 and decompensation unrelated to HCC occurred in 13 patients. The number of HCC patients was similar in both groups. The probability of complication-free survival was not significantly different between treated and untreated patients (98% and 72.3% vs 90% and 70.7% at 12 and 24 mo, respectively, P = .59). The median time until complication occurrence was 17.1 months in the treated group vs 13.6 months in the untreated group (P = .2). CONCLUSIONS This randomized controlled trial showed that a 2-year course of IFN has little or no impact on complication-free survival in patients with high-risk compensated HCV cirrhosis.
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25
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Zaghla H, Selby RR, Chan LS, Kahn JA, Donovan JA, Jabbour N, Genyk Y, Mateo R, Gagandeep S, Sher LS, Ramicone E, Fong TL. A comparison of sirolimus vs. calcineurin inhibitor-based immunosuppressive therapies in liver transplantation. Aliment Pharmacol Ther 2006; 23:513-20. [PMID: 16441472 DOI: 10.1111/j.1365-2036.2006.02770.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND Sirolimus is a potent immunosuppressive agent whose role in liver transplantation has not been well-described. AIM To evaluate the efficacy and side-effects of sirolimus-based immunosuppression in liver transplant patients. METHODS Retrospective analysis of 185 patients who underwent orthotopic liver transplantation. Patients were divided into three groups: group SA, sirolimus alone (n = 28); group SC, sirolimus with calcineurin inhibitors (n =56) and group CNI, calcineurin inhibitors without sirolimus (n = 101). RESULTS One-year patient and graft survival rates were 86.5% and 82.1% in group SA, 94.6% and 92.9% in group SC, and 83.2% and 75.2% in group CNI (P = N.S.). The rates of acute cellular rejection at 12 months were comparable among the three groups. At the time of transplantation, serum creatinine levels were significantly higher in group SA, but mean creatinine among the three groups at 1 month was similar. More patients in group SA required dialysis before orthotopic liver transplantation (group SA, 25%; group SC, 9%; group CNI, 5%; P = 0.008), but at 1 year, post-orthotopic liver transplantation dialysis rates were similar. CONCLUSIONS Sirolimus given alone or in conjunction with calcineurin inhibitors appears to be an effective primary immunosuppressant regimen for orthotopic liver transplantation patients. Further studies to evaluate the efficacy and side-effect profile of sirolimus in liver transplant patients are warranted.
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Affiliation(s)
- H Zaghla
- Liver Transplant Program, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
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26
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Dienstag JL, McHutchison JG. American Gastroenterological Association technical review on the management of hepatitis C. Gastroenterology 2006; 130:231-64; quiz 214-7. [PMID: 16401486 DOI: 10.1053/j.gastro.2005.11.010] [Citation(s) in RCA: 267] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Jules L Dienstag
- Gastrointestinal Unit (Medical Services) Massachusetts General Hospital, Department of Medicine and Office of the Dean for Medical Education, Harvard Medical School, Boston, Massachusetts, USA
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27
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Abstract
This article summarizes the current therapies, with particular emphasis on antiviral therapy. Because these alternatives have substantial limitations, pretransplant or early post-transplant recognition of patients with high risk of severe post-transplantation outcome is desirable to target these patients for intervention. Alternatively, the implementation of measures aimed at reducing or avoiding factors known to be associated with an aggressive recurrence is an additional strategy that needs to be explored.
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Affiliation(s)
- Marina Berenguer
- Hospital Universitario La FE, Servicio de Medicina Digestiva, Avenida Campanar 21, Valencia, 46009 Spain.
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28
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Abstract
Hepatitis C is found in approximately a third of patients infected with HIV. Therapy of hepatitis C in HIV patients is very important from several view points. First, hepatitis C in the setting of immunosuppression may progress faster, although recent data show that mortality from liver disease was decreased in highly active antiretroviral therapy. HIV/hepatitis C coinfection is associated with more frequent elevation in liver tests (drug-induced liver injury) during highly active antiretroviral therapy, and in some studies, hepatitis C has been associated with lower CD4+ recoveries. The therapeutic standard of care is a combination of peginterferon and ribavirin at a fixed dose, 800 mg/day, although higher ribavirin doses may further improve virologic outcomes. In patients that do not respond virologically, maintenance therapy with peginterferon monotherapy is a potential avenue to stem the advance of liver fibrosis, although controlled data in coinfected patients are needed to issue formal recommendations.
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Affiliation(s)
- Tami Daugherty
- California Pacific Medical Center, 2340 Clay Street, 2nd Floor, San Francisco, CA 94115, USA.
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29
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SHARMA PRATIMA, VARGAS HUGOE, RAKELA JORGE. Monitoring and Care of the Patient Before Liver Transplantation. TRANSPLANTATION OF THE LIVER 2005:473-489. [DOI: 10.1016/b978-0-7216-0118-2.50037-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Suárez F, Otero A, Gonzalez B, Gómez-Gutiérrez M, Arnal F, Vazquez JL. Retransplantation for hepatitis c–related cirrhosis under long-term pegylated interferon therapy. Transplant Proc 2004; 36:775-7. [PMID: 15110659 DOI: 10.1016/j.transproceed.2004.03.028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
INTRODUCTION Because of an increased organ shortage, one of the most controversial questions is whether hepatic retransplantation should be offered to transplant recipients with hepatitis C virus (HCV)-related graft failure because of their worse survival and the inevitable denial of other patients to access to primary transplantation. The objective of the present study was to review our experience with HCV-infected transplant recipients undergoing re-orthotopic liver transplantation (OLT) for HCV graft cirrhosis and receiving pegylated interferon and ribavirin on a prophylactic basis. RESULTS With a median follow-up of 26 months, all 5 patients are alive with stable graft function. Four patients are still receiving pegylated interferon at a mean duration of 20 months (range, 15-32 months). Although none of the patients has cleared HCV RNA by polymerase chain reaction the mean serum levels have decreased significantly when compared with pre-retransplantation amounts. One year after re-OLT, both grade and fibrosis stage had significantly decreased; the rate of post-retransplantation fibrosis progression was significantly lower than that pre-retransplantation (3.4 +/- 0.2 vs 0.6 +/- 0.3; P <.05).
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Affiliation(s)
- F Suárez
- Liver Transplant Unit, Hospital Juan Canalejo, La Coruña, Spain.
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Zarski JP, Hilleret MN. Treatment of patients with decompensated post-hepatitis C cirrhosis before liver transplantation: strategy to prevent hepatitis C virus (HCV) recurrence? J Hepatol 2003; 39:435-6. [PMID: 12927932 DOI: 10.1016/s0168-8278(03)00285-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
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Affiliation(s)
- M Berenguer
- Servicio de Medicina Digestiva, Hospital Universitario La Fe, Avda Campanar 21, Valencia, 46009, Spain.
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