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Zhu SS, Zeng QL, Dong Y, Xu ZQ, Wang LM, Chen DW, Gan Y, Wang FC, Yan JG, Cao LL, Wang P, Han J, Zhang XX, Zhang Z, Zhang HF, Wang FS. Interferon-α plus ribavirin yields 98 % sustained virologic response in children aged 1-5 years with iatrogenic chronic hepatitis C. Hepatol Int 2015; 9:578-585. [PMID: 26449425 DOI: 10.1007/s12072-015-9671-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Accepted: 07/19/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND OBJECTIVES The clinical features and efficacies of antivirals for children with hepatitis C virus (HCV) infections that are acquired through different transmission routines are poorly understood worldwide. This study investigated the clinical characteristics of children who were infected via iatrogenic means and analyzed the efficacy of antiviral therapy in children with chronic hepatitis C (CHC). METHODS In total, 256 children with HCV infections aged 1 to 5 years were enrolled and surveyed. Interferon-α plus ribavirin was administered to 162 children with CHC for 24 or 48 weeks. The sustained virologic response (SVR) at 24 weeks post-treatment was determined. RESULTS The median duration of infection was 11.5 (range 6-24) months. The median age was 2.7 years, and 64.5 % of the subjects were male. Ninety-three children (36.3 %, 93/256) exhibited spontaneous resolution of the HCV infection. The remaining 163 (63.7 %) were HCV RNA-positive and had HCV genotypes 1b and 2a, which were identified in 42 and 58 %, respectively, of the 133 tested children. Liver biopsies were performed in all HCV RNA-detectable children. A total of 23.9 % cases exhibited grade 2 activity, and 30.1 % exhibited stage 2/3 liver fibrosis. The serum HCV RNA levels were positively correlated with the aminotransferases. Of the 162 treated CHC children, 158 (97.5 %) achieved SVR. The side effects were mild, and 158 (97.5 %) of the treated patients tolerated the treatment well. CONCLUSIONS This study revealed that histological liver disease can be present within 6-24 months of acquiring an HCV infection in children aged 1-5 years. Interferon-α plus ribavirin therapy is a highly effective and cost-effective means of managing children with early-stage chronic HCV infection.
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Affiliation(s)
- Shi-Shu Zhu
- Treatment and Research Center for Children's Liver Disease, Beijing 302 Hospital, Beijing, 100039, China
| | - Qing-Lei Zeng
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, 100039, China
| | - Yi Dong
- Treatment and Research Center for Children's Liver Disease, Beijing 302 Hospital, Beijing, 100039, China
| | - Zhi-Qiang Xu
- Treatment and Research Center for Children's Liver Disease, Beijing 302 Hospital, Beijing, 100039, China
| | - Li-Min Wang
- Treatment and Research Center for Children's Liver Disease, Beijing 302 Hospital, Beijing, 100039, China
| | - Da-Wei Chen
- Treatment and Research Center for Children's Liver Disease, Beijing 302 Hospital, Beijing, 100039, China
| | - Yu Gan
- Treatment and Research Center for Children's Liver Disease, Beijing 302 Hospital, Beijing, 100039, China
| | - Fu-Chuan Wang
- Treatment and Research Center for Children's Liver Disease, Beijing 302 Hospital, Beijing, 100039, China
| | - Jian-Guo Yan
- Treatment and Research Center for Children's Liver Disease, Beijing 302 Hospital, Beijing, 100039, China
| | - Li-Li Cao
- Treatment and Research Center for Children's Liver Disease, Beijing 302 Hospital, Beijing, 100039, China
| | - Pu Wang
- Treatment and Research Center for Children's Liver Disease, Beijing 302 Hospital, Beijing, 100039, China
| | - Jin Han
- Genetic Testing Center, Beijing 302 Hospital, Beijing, 100039, China
| | - Xue-Xiu Zhang
- The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, 100039, China
| | - Zheng Zhang
- The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, 100039, China
| | - Hong-Fei Zhang
- Treatment and Research Center for Children's Liver Disease, Beijing 302 Hospital, Beijing, 100039, China.
| | - Fu-Sheng Wang
- The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, 100039, China.
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Hunyady B, Gerlei Z, Gervain J, Horváth G, Lengyel G, Pár A, Rókusz L, Szalay F, Telegdy L, Tornai I, Werling K, Makara M. [In Process Citation]. Orv Hetil 2015; 156 Suppl 1:3-23. [PMID: 26039413 DOI: 10.1556/oh.2015.30107] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Approximately 70,000 people are infected with hepatitis C virus in Hungary, and more than half of them are not aware of their infection. From the point of infected individuals early recognition and effective treatment of related liver injury may prevent consequent advanced liver diseases and complications (liver cirrhosis, liver failure and liver cancer) and can increase work productivity and life expectancy. From a socioeconomic aspect, this could also prevent further spread of the virus as well as reduce substantially long term financial burden of related morbidity. Pegylated interferon + ribavirin dual therapy, which is available in Hungary since 2003, can clear the virus in 40-45% of previously not treated (naïve), and in 5-21% of previous treatment-failure patients. Addition of a direct acting first generation protease inhibitor drug (boceprevir or telaprevir) to the dual therapy increases the chance of sustained viral response to 63-75% and 59-66%, respectively. These two protease inhibitors are available and financed for a segment of Hungarian patients since May 2013. Between 2013 and February 2015, other direct acting antiviral interferon-free combination therapies have been registered for the treatment of chronic hepatitis C, with a potential efficacy over 90% and typical short duration of 8-12 weeks. Indication of therapy includes exclusion of contraindications to the drugs and demonstration of viral replication with consequent liver injury, i.e., inflammation and / or fibrosis in the liver. Non-invasive methods (elastography and biochemical methods) are accepted and preferred for staging liver damage (fibrosis). For initiation of treatment as well as for on-treatment decisions, accurate and timely molecular biology tests are mandatory. Eligibility for treatment is a subject of individual central medical review. Due to budget limitations therapy is covered only for a proportion of patients by the National Health Insurance Fund. Priority is given to those with urgent need based on a Hungarian Priority Index system reflecting primarily the stage of liver disease, and considering also additional factors, i.e., activity and progression of liver disease, predictive factors of treatment and other special issues. Approved treatments are restricted to the most cost-effective combinations based on the cost per sustained viral response value in different patient categories with consensus between professional organizations, National Health Insurance Fund and patient organizations. More expensive therapies might be available upon co-financing by the patient or a third party. Interferon-free treatments and shorter therapy durations preferred as much as financially feasible. A separate budget is allocated to cover interferon-free treatments for the most-in-need interferon ineligible/intolerant patients, and for those who have no more interferon-based therapy option. Orv. Hetil., 2015, 156(Suppl. 1), 3-23.
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Affiliation(s)
- Béla Hunyady
- 1 Somogy Megyei Kaposi Mór Oktató Kórház Belgyógyászati Osztály Kaposvár Tallián Gy. u. 20-32. 7400
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3
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Gupta M, Bahirwani R, Levine MH, Malik S, Goldberg D, Reddy KR, Shaked A. Outcomes in pediatric hepatitis C transplant recipients: analysis of the UNOS database. Pediatr Transplant 2015; 19:153-63. [PMID: 25495572 DOI: 10.1111/petr.12408] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/07/2014] [Indexed: 12/20/2022]
Abstract
HCV may lead to the development of ESLD in late childhood and, consequently, contributes to the need for liver transplantation. The aim of this study was to examine post-transplant outcomes in HCV-positive pediatric patients with ESLD from any cause and to determine the impact of the PELD scoring system, introduced in February 2002, on post-transplant patient and graft survival. A retrospective analysis of the UNOS database from 1994 to 2010 was performed to assess graft and patient survival in pediatric HCV-seropositive liver transplant recipients. Graft survival and patient survival comparing subjects in the pre-PELD era and post-PELD era were analyzed using Kaplan-Meier statistics. Factors associated with survival were identified using Cox regression analysis. Of 120 pediatric HCV transplant recipients, 80 were transplanted in the pre-PELD era and 40 were transplanted post-PELD. Median serum total bilirubin, INR, and creatinine were 4.8 mg/dL, 1.6, and 0.7 mg/dL in the pre-PELD era vs. 5.5 mg/dL, 1.7, and 0.6 mg/mL, respectively, in the post-PELD era (p NS). One-yr graft survival in the pre-PELD vs. post-PELD era was 65.0% and 89.7%, respectively (p < 0.01); corresponding three-yr graft survival was 57.3% vs. 76.2% (p = 0.04). One-yr patient survival in the pre-PELD vs. post-PELD era was 79.0% and 97.5%, respectively (p < 0.01); corresponding three-yr survival was 79.0% vs. 89.4% (p = 0.17). Twenty-eight patients (23.3%) were retransplanted: 24 (30%) in the pre-PELD era (median time to retransplant 272 days) and four (10%) in the post-PELD era (median time to retransplant 586 days). Early follow-up demonstrates a trend toward improved pediatric HCV liver transplant graft and patient survival in the post-PELD era. Superior outcomes may be attributed to pretransplant factors, improved surgical technique and better treatment options for HCV infection.
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Affiliation(s)
- Meera Gupta
- Division of Transplantation, Department of Surgery, University of Pennsylvania, Philadelphia, PA, USA
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Pawlowska M. Pegylated IFN-α-2a and ribavirin in the treatment of hepatitis C infection in children. Expert Opin Drug Saf 2015; 14:343-8. [PMID: 25599750 DOI: 10.1517/14740338.2015.1005599] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
The epidemiology, natural history and efficacy of treatment for chronic hepatitis C in children are presented. An increase in the number of vertical infections of this etiology is suggested. In children, especially in those vertically infected, spontaneous elimination of hepatitis C virus (HCV) is observed more often than it is in adults. The most common HCV genotype detected in children is genotype 1, but Italian researchers have described an increase of infection with genotypes 3 and 4 HCV in children in recent years. In the context of recent opinions suggesting a more rapid progression of HCV 3 genotype infection, treatment of these children should begin immediately. The high efficacy (sustained viral response > 50%), safety (few adverse events with less intensity as compared to adults) and good tolerance of therapy with pegylated IFN α-2a and ribavirin have been revealed in children. The differences in the efficacy and tolerability of HCV treatment between children and adults are described. A recommendation for inclusion and monitoring parameters of children's physical and mental development during HCV treatment is presented. Regarding new anti-HCV therapies with very high efficacy, including IFN-free treatment, the introduction of these therapies to children is recommended.
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Affiliation(s)
- Malgorzata Pawlowska
- Collegium Medicum Nicolaus Copernicus University, Department of Children Infectious Diseases and Hepatology , Floriana 12, 85-830 Bydgoszcz , Poland +48 52 3255605 ;
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Sánchez-Ávila JF, Dehesa-Violante M, Méndez-Sánchez N, Bosques-Padilla F, Castillo-Barradas M, Castro-Narro G, Cisneros-Garza L, Chirino-Sprung RA, García-Juarez I, Gonzalez-Huezo MS, Malé-Velazquez R, Moreno-Alcántar R, Muñoz-Espinoza L, Ramos-Gómez M, Rizo-Robles MT, Sandoval-Salas R, Sierra-Madero J, Torres-Ibarra MDR, Vazquez-Frias R, Wolpert-Barraza E. Mexican consensus on the diagnosis and management of hepatitis C infection. Ann Hepatol 2015; 14 Suppl 1:5-48. [PMID: 25983318 DOI: 10.1016/s1665-2681(19)30815-4] [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: 02/06/2025]
Affiliation(s)
| | | | | | | | | | | | - Laura Cisneros-Garza
- Liver Disease Clinic, Hospital San José TEC de Monterrey Monterrey, Nuevo Leon, Mexico
| | | | | | | | - René Malé-Velazquez
- Instituto de Salud Digestiva y Hepáticas. Department of Gastroenterology, Hospital del Carmen Guadalajara, Jalisco, Mexico
| | - Rosalba Moreno-Alcántar
- Department of Gastroenterology, Hospital de Especialidades CMN SXXI, IMSS, Mexico City, Mexico
| | - Linda Muñoz-Espinoza
- Liver Unit, Hospital Universitario J.E. González. UANL Monterrey, Nuevo Leon, Mexico
| | - Mayra Ramos-Gómez
- Department of Gastroenterology, CMN 20 de Noviembre, ISSSTE,, Mexico City, Mexico
| | - Ma Teresa Rizo-Robles
- Department of Gastroenterology, CMN La Raza, IMSS. Mexican Association of Hepatology, Mexico City, Mexico
| | - Ricardo Sandoval-Salas
- Department of Gastroenterology, Hospital de Especialidades, CMN Siglo XXI, IMSS, Mexico City, Mexico
| | | | | | - Rodrigo Vazquez-Frias
- Department of Gastroenterology, Hospital Infantil de México "Federico Gómez", SSA, Mexico City, Mexico
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Low prevalence of hepatitis B and C virus markers among children and adolescents. BIOMED RESEARCH INTERNATIONAL 2014; 2014:324638. [PMID: 25093164 PMCID: PMC4100382 DOI: 10.1155/2014/324638] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/19/2014] [Revised: 05/22/2014] [Accepted: 05/27/2014] [Indexed: 12/11/2022]
Abstract
This study aimed to determine the prevalence of HBV and HCV among children and adolescents attending schools and daycare centres in Rio de Janeiro State, located in southern Brazil. Serum samples from 1,217 individuals aged 0 to 18 years were collected from 1999 to 2012 and tested for HBsAg, total anti-HBc, anti-HBs, and anti-HCV by ELISA. Reactive HBsAg and anti-HBc samples were tested for HBV DNA. Reactive anti-HCV samples were tested for HCV RNA and genotyped by RFLP. HBsAg was detected in 1.8% of individuals, and total anti-HBc was detected among 3.6% of individuals. Anti-HBs reactivity was found among 25.3% (322/1,217) of the individuals and increased from 6.28% in the years 1999-2000 to 76.2% in the years 2001–2012 (P < 0.0001). HBV DNA was detected in 18 of 51 individuals who presented with HBsAg or isolated anti-HBc, and nine were considered occult hepatitis B cases. Three individuals were anti-HCV- and HCV RNA-positive: two of them were infected with genotype 1, and the other was infected with genotype 3. Low levels of HBV and HCV markers were observed in children and adolescents. HBV immunity increased during the period of study, indicating that childhood universal HBV vaccination has been effective for controlling HBV infection in Brazil.
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Hunyady B, Gervain J, Horváth G, Makara M, Pár A, Szalay F, Telegdy L, Tornai I. [Diagnosis, treatment, and follow-up of hepatitis C-virus related liver disease. Hungarian national consensus guideline]. Orv Hetil 2014; 155 Suppl:3-24. [PMID: 24631886 DOI: 10.1556/oh.2013.29893] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Approximately 70 000 people are infected with hepatitis C virus in Hungary, more than half of whom are not aware of their infection. Early recognition and effective treatment of related liver injury may prevent consequent advanced liver diseases (liver cirrhosis and liver cancer) and its complications. In addition, it may increase work productivity and life expectancy of infected individual, and can prevent further viral transmission. Early recognition can substantially reduce the long term financial burden of related morbidity from socioeconomic point of view. Pegylated interferon + ribavirin dual therapy, which is available in Hungary since 2003, can kill the virus in 40-45% of previously not treated (naïve), and in 5-21% of previous treatment-failure patients. Addition of two direct acting first generation protease inhibitor drugs (boceprevir and telaprevir) to the dual therapy increased the chance of sustained clearance of virus to 63-75% and 59-66%, respectively. These two protease inhibitor drugs are available and financed for a segment of Hungarian patients since May 2013. Indication of therapy includes exclusion of contraindications to the drugs and demonstration of viral replication with consequent liver injury, i.e., inflammation and/or fibrosis in the liver. For initiation of treatment as well as for on-treatment decisions accurate and timely molecular biology tests are mandatory. Staging of liver damage (fibrosis) non-invasive methods (transient elastography and biochemical methods) are acceptable to avoid concerns of patients related to liver biopsy. Professional decision for treatment is balanced against budget limitations in Hungary, and priority is given to those with urgent need using a national Priority Index system reflecting stage of liver disease as well as additional factors (activity and progression of liver disease, predictive factors and other special circumstances). All naïve patients are given a first chance with dual therapy. Those with genotype 1 infection and with on-treatment or historic failure to dual therapy are eligible to receive protease inhibitor based triple therapy provided, they reach financial cutoff eligibility based on Priority Index. Duration of therapy is usually 48 weeks in genotype 1 with a response-guided potential to reduce duration for non-cirrhotic patients. Patients with non-1 genotypes are treated with dual therapy (without protease inhibitors) for a genotype and response driven duration of 16, 24, 48, or 72 week. Careful monitoring for early recognition and management of side-effects as well as viral response and potential breakthrough during protease-inhibitor therapy are recommended.
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Affiliation(s)
- Béla Hunyady
- Somogy Megyei Kaposi Mór Oktató Kórház Belgyógyászati Osztály Kaposvár Tallián Gyula u. 20-32. 7400 Pécsi Tudományegyetem, Általános Orvostudományi Kar I. Belgyógyászati Klinika Pécs
| | - Judit Gervain
- Szent György Egyetemi Oktató Kórház I. Belgyógyászat és Molekuláris Diagnosztikai Laboratórium Székesfehérvár
| | - Gábor Horváth
- Szent János Kórház és Észak-budai Egyesített Kórházak Hepatológiai Szakrendelés Budapest
| | - Mihály Makara
- Egyesített Szent István és Szent László Kórház Budapest
| | - Alajos Pár
- Pécsi Tudományegyetem, Általános Orvostudományi Kar I. Belgyógyászati Klinika Pécs
| | - Ferenc Szalay
- Semmelweis Egyetem, Általános Orvostudományi Kar I. Belgyógyászati Klinika Budapest
| | | | - István Tornai
- Debreceni Egyetem, Általános Orvostudományi Kar, Orvos- és Egészségtudományi Centrum Belgyógyászati Intézet Debrecen
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Naghi SE, Abdel-Ghaffar TY, El-Karaksy H, Abdel-Aty EF, El-Raziky MS, Allam AA, Helmy H, El-Araby HA, Behairy BE, El-Guindi MA, El-Sebaie H, Abdel-Ghaffar AY, Ehsan NA, El-Hennawy AM, Sira MM. Safety and efficacy of Hansenula-derived PEGylated-interferon alpha-2a and ribavirin combination in chronic hepatitis C Egyptian children. World J Gastroenterol 2014; 20:4681-4691. [PMID: 24782620 PMCID: PMC4000504 DOI: 10.3748/wjg.v20.i16.4681] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2013] [Revised: 01/07/2014] [Accepted: 03/04/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the safety and efficacy of a Hansenula-derived PEGylated (polyethylene glycol) interferon (IFN)-alpha-2a (Reiferon Retard) plus ribavirin customized regimen in treatment-naïve and previously treated (non-responders and relapsers) Egyptian children with chronic hepatitis C infection. METHODS Forty-six children with chronic hepatitis C virus (HCV) infection were selected from three tertiary pediatric hepatology centers. Clinical and laboratory evaluations were undertaken. Quantitative polymerase chain reaction (PCR) for HCV-RNA was performed before starting treatment, and again at 4, 12, 24, 48, 72 wk during treatment and 6 mo after treatment cessation. All patients were assigned to receive a weekly subcutaneous injection of PEG-IFN-alpha-2a plus daily oral ribavirin for 12 wk. Thirty-four patients were treatment-naïve and 12 had a previous treatment trial. Patients were then divided according to PCR results into two groups. Group I included patients who continued treatment on a weekly basis (7-d schedule), while group II included patients who continued treatment on a 5-d schedule. Patients from either group who were PCR-negative at week 48, but had at least one PCR-positive test during therapy, were assigned to have an extended treatment course up to 72 wk. The occurrence of adverse effects was assessed during treatment and follow up. The study was registered at www.ClinicalTrials.gov (NCT02027493). RESULTS Only 11 out of 46 (23.9%) patients showed a sustained virological response (SVR), two patients were responders at the end of treatment; however, they were lost to follow up at 6 mo post treatment. Breakthrough was seen in 18 (39.1%) patients, one patient (2.17%) showed relapse and 14 (30.4%) were non-responders. Male gender, short duration of infection, low viral load, mild activity, and mild fibrosis were the factors related to a better response. On the other hand, patients with high viral load and absence of fibrosis failed to respond to treatment. Before treatment, liver transaminases were elevated. After commencing treatment, they were normalized in all patients at week 4 and were maintained normal in responders till the end of treatment, while they increased again significantly in non-responders (P = 0.007 and 0.003 at week 24 and 72 respectively). The 5-d schedule did not affect the response rate (1/17 had SVR). Treatment duration (whether 48 wk or extended course to 72 wk) gave similar response rates (9/36 vs 2/8 respectively; P = 0.49). Type of previous treatment (short acting IFN vs PEG-IFN) did not affect the response to retreatment. On the other hand, SVR was significantly higher in previous relapsers than in previous non-responders (P = 0.039). Only mild reversible adverse effects were observed and children tolerated the treatment well. CONCLUSION Reiferon Retard plus ribavirin combined therapy was safe. Our customized regimen did not influence SVR rates. Further trials on larger numbers of patients are warranted.
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