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1
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Liu CH, Kao JH. Pan-genotypic direct-acting antivirals for patients with hepatitis C virus infection and chronic kidney disease stage 4 or 5. Hepatol Int 2022; 16:1001-1019. [PMID: 35876967 PMCID: PMC9309604 DOI: 10.1007/s12072-022-10390-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 07/03/2022] [Indexed: 12/17/2022]
Abstract
Hepatitis C virus (HCV) infection is a major health problem with significant clinical and economic burdens in patients with chronic kidney disease (CKD) stage 4 or 5. Current guidelines recommend pan-genotypic direct-acting antivirals (DAAs) to be the first-line treatment of choice for HCV. This review summarizes the updated knowledge regarding the epidemiology, natural history, public health perspectives of HCV in patients with CKD stage 4 or 5, including those on maintenance dialysis, and the performance of pan-genotypic DAAs in these patients. The prevalence and incidence of HCV are much higher in patients with CKD stage 4 or 5 than in the general population. The prognosis is compromised if HCV patients are left untreated regardless of kidney transplantation (KT). Following treatment-induced HCV eradication, patient can improve the health-related outcomes by maintaining a long-term aviremic state. The sustained virologic response (SVR12) rates and safety profiles of pan-genotypic DAAs against HCV are excellent irrespective of KT. No dose adjustment of pan-genotypic DAAs is required across CKD stages. Assessing drug-drug interactions (DDIs) before HCV treatment is vital to secure on-treatment safety. The use of prophylactic or preemptive pan-genotypic DAAs in HCV-negative recipients who receive HCV-positive kidneys has shown promise in shortening KT waiting time, achieving excellent on-treatment efficacy and safety, and maintaining post-KT patient and graft survival. HCV elimination is highly feasible through multifaceted interventions, including mass screening, treatment scale-up, universal precautions, and post-SVR12 reinfection surveillance.
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Affiliation(s)
- Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and Hospital, 7 Chung-Shan South Road, Taipei, 10002 Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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2
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Oleic Acid-Based Self Micro-Emulsifying Delivery System for Enhancing Antifungal Activities of Clotrimazole. Pharmaceutics 2022; 14:pharmaceutics14030478. [PMID: 35335854 PMCID: PMC8951188 DOI: 10.3390/pharmaceutics14030478] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 02/17/2022] [Accepted: 02/18/2022] [Indexed: 02/04/2023] Open
Abstract
Due to the increasing rate of drug resistance in Candida spp., higher doses of antifungal agents are being used resulting in toxicity. Drug delivery systems have been shown to provide an effective approach to enhance the efficacy and reduce the toxicity of antifungal agents. Oleic acid was revealed to effectively inhibit biofilm formation, hence reducing the virulence of Candida albicans. In this study, oleic acid-based self micro-emulsifying delivery systems (OA-SMEDDS) were developed for delivering clotrimazole (CLT). Based on the pseudo-ternary phase diagram and loading capacity test, the optimal ratio of OA-SMEDDS with CLT was selected. CLT-loaded OA-SMEDDS not only bears a higher drug loading capacity but also maintains good storage stability. The minimum inhibitory concentration (MIC50) of CLT-loaded OA-SMEDDS (0.01 μg/mL) in Candida albicans was significantly lower than that of CLT dissolved in DMSO (0.04 μg/mL). Moreover, we showed CLT-loaded OA-SMEDDS could effectively prevent biofilm formation and destroy the intact biofilm structure of Candida albicans. Furthermore, a CLT-loaded OA-SMEDDS gel was developed and evaluated for its antifungal properties. Disk diffusion assay indicated that both CLT-loaded OA-SMEDDS and CLT-loaded OA-SMEDDS gels were more effective than commercially available products in inhibiting the wild-type and drug-resistant species of Candida.
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Ding Y, Xu J, Cheng LB, Huang YQ, Wang YQ, Li H, Li Y, Ji JY, Zhang JH, Zhao L. Effect of Emodin on Coxsackievirus B3m-Mediated Encephalitis in Hand, Foot, and Mouth Disease by Inhibiting Toll-Like Receptor 3 Pathway In Vitro and In Vivo. J Infect Dis 2021; 222:443-455. [PMID: 32115640 DOI: 10.1093/infdis/jiaa093] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Accepted: 02/28/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Encephalitis in hand, foot, and mouth disease (HFMD) is a serious threat to children's health and life. Toll-like receptor 3 (TLR3) is an innate immune-recognition receptor that can recognize virus and initiate innate immune responses. Emodin has the effects of anti-inflammatory and regulating immune function, but the mechanism is not very clear. METHODS Cells and mice were pretreated with coxsackievirus B3m (CVB3) and treated with emodin. The messenger ribonucleic acid (mRNA) and protein levels of TLR3 and downstream molecules were detected by quantitative real-time polymearse chain reaction and western blotting analysis, respectively. TLR3 expression was also downregulated by anti-TLR3 antibody (TLR3Ab) or small interfering RNA (siRNA). Pathological changes were assessed with hematoxylin and eosin staining. Immunohistochemistry was used to examine the expression of TLR3 in brain tissues. The expression of interleukin (IL)-6, nuclear factor (NF)-κB, and interferon (IFN)-β in serum were tested with enzyme-linked immunosorbent assay. RESULTS Emodin decreased the mRNA and protein levels of TLR3 and downstream molecules in vitro and in vivo. After downregulating TLR3 using anti-TLR3Ab or siRNA, emodin could still decrease the mRNA and protein levels of TLR3 and downstream molecules. Emodin also displayed notable effects on pathology, TLR3 protein in brain tissues, and expression of IL-6, NF-κB, IFN-β, in serum. CONCLUSIONS Emodin exerts a protective effect in CVB3-mediated encephalitis in HFMD by inhibiting the TLR3 pathway.
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Affiliation(s)
- Yan Ding
- Department of Infectious Diseases and Immunology, Medical and Health Center for Women and Children, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People's Republic of China
| | - Jie Xu
- Clinical College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei Province, People's Republic of China.,Department of Hepatology, Yichang Hospital of Traditional Chinese Medicine, Yichang, Hubei Province, People's Republic of China
| | - Liang-Bin Cheng
- Department of Liver Diseases, Hubei Hospital of Traditional Chinese Medicine, Wuhan, Hubei Province, People's Republic of China
| | - Yong-Qian Huang
- Department of Neurology, Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei Province, People's Republic of China
| | - You-Qin Wang
- Department of Pediatrics, Central Hospital, Hubei University of Medicine, Suizhou, Hubei Province, People's Republic of China
| | - Hui Li
- Department of Integrated Traditional Chinese Medicine and Western Medicine, Tianyou Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei Province, People's Republic of China
| | - Yu Li
- Department of Vascular Surgery, Yichang Central People's Hospital, Yichang, Hubei Province, People's Republic of China
| | - Jing-Yu Ji
- Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People's Republic of China
| | - Ji-Hong Zhang
- Department of Hepatology, Yichang Hospital of Traditional Chinese Medicine, Yichang, Hubei Province, People's Republic of China
| | - Lei Zhao
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People's Republic of China
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4
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Yen HH, Su PY, Zeng YH, Liu IL, Huang SP, Hsu YC, Chen YY, Yang CW, Wu SS, Chou KC. Glecaprevir-pibrentasvir for chronic hepatitis C: Comparing treatment effect in patients with and without end-stage renal disease in a real-world setting. PLoS One 2020; 15:e0237582. [PMID: 32790715 PMCID: PMC7425913 DOI: 10.1371/journal.pone.0237582] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 07/29/2020] [Indexed: 12/12/2022] Open
Abstract
Introduction Chronic hepatitis C virus (HCV) infection is increasingly observed in patients with renal disease. With the introduction of glecaprevir/pibrentasvir (GLE/PIB) as a pan-genotype therapy for HCV, treatment efficacy is expected to rise. Materials and methods This retrospective study evaluated the efficacy and safety of GLE/PIB treatment in adults with HCV infection and end-stage renal disease (ESRD). The primary end point was sustained virological response (SVR) observed 12 weeks after completed treatment. Results We enrolled 235 patients, including 44 patients with ESRD. Median age was 60 years, and 48% were males. Twenty-two percent had cirrhosis. HCV genotypes 1 (43%) and 2 (41%) were the most common. The overall SVR rate was 96.6%. Patients with ESRD were older than those without (67.6 years vs 58.3 years, p < 0.001) and trended toward having a higher prevalence of cirrhosis (32% vs 19%, p = 0.071). A significant proportion of patients with ESRD complained of skin itching during treatment (61% vs 26%, p < 0.001), and the SVR rate were similar between these two groups (95.45% vs 96.86%, p = 0.644). Conclusions Despite a higher rate of pruritus among patients with ESRD, GLE/PIB-based therapy achieved similarly high SVR rates among patients with and without ESRD.
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Affiliation(s)
- Hsu-Heng Yen
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- General Education Center, Chienkuo Technology University, Changhua, Taiwan
- * E-mail: , (HHY); (KCC)
| | - Pei-Yuan Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Ya-Huei Zeng
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - I-Ling Liu
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Siou-Ping Huang
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Yu-Chun Hsu
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Yang-Yuan Chen
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Chia-Wei Yang
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Shun-Sheng Wu
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Kun-Ching Chou
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
- * E-mail: , (HHY); (KCC)
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5
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Salvadori M, Tsalouchos A. Hepatitis C and renal transplantation in era of new antiviral agents. World J Transplant 2018; 8:84-96. [PMID: 30148074 PMCID: PMC6107518 DOI: 10.5500/wjt.v8.i4.84] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Revised: 04/17/2018] [Accepted: 05/30/2018] [Indexed: 02/05/2023] Open
Abstract
Data from World Health Organization estimates that the hepatitis C virus (HCV) prevalence is 3% and approximately 71 million persons are infected worldwide. HCV infection is particularly frequent among patients affected by renal diseases and among those in dialysis treatment. In addition to produce a higher rate of any cause of death, HCV in renal patients and in renal transplanted patients produce a deterioration of liver disease and is a recognized cause of transplant glomerulopathy, new onset diabetes mellitus and lymphoproliferative disorders. Treatment of HCV infection with interferon alpha and/or ribavirin had a poor efficacy. The treatment was toxic, expensive and with limited efficacy. In the post-transplant period was also cause of severe humoral rejection. In this review we have highlighted the new direct antiviral agents that have revolutionized the treatment of HCV both in the general population and in the renal patients. Patients on dialysis or with low glomerular filtration rate were particularly resistant to the old therapies, while the direct antiviral agents allowed achieving a sustained viral response in 90%-100% of patients with a short period of treatment. This fact to date allows HCV patients to enter the waiting list for transplantation easier than before. These new agents may be also used in renal transplant patients HCV-positive without relevant clinical risks and achieving a sustained viral response in almost all patients. New drug appears in the pipeline with increased profile of efficacy and safety. These drugs are now the object of several phases II, III clinical trials.
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Affiliation(s)
- Maurizio Salvadori
- Department of Transplantation Renal Unit, Careggi University Hospital, Florence 50139, Italy
| | - Aris Tsalouchos
- Nephrology and Dialysis Unit, Saints Cosmas and Damian Hospital, Pescia 51017, Italy
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6
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He YL, Yang SJ, Hu CH, Dong J, Gao H, Yan TT, Liu JF, Yang Y, Ren DF, Zhu L, Zhao YR, Chen TY. Safety and efficacy of sofosbuvir-based treatment of acute hepatitis C in end-stage renal disease patients undergoing haemodialysis. Aliment Pharmacol Ther 2018; 47:526-532. [PMID: 29250808 DOI: 10.1111/apt.14429] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2017] [Revised: 07/24/2017] [Accepted: 10/31/2017] [Indexed: 12/27/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection in patients undergoing haemodialysis is prevalent and aggressive. The treatment of chronic hepatitis C has been revolutionised by the advent of direct-acting antivirals (DAAs). However, the safety, efficacy, and tolerance of DAAs in the treatment of acute HCV infection in patients with end-stage renal disease who are on haemodialysis are unknown. AIM To evaluate the safety and efficacy of sofosbuvir plus daclatasvir in this specific, difficult-to-treat population. METHODS We conducted a prospective and observational study of end-stage renal disease patients who were undergoing haemodialysis and were acutely infected with HCV. Patients received a half dose of sofosbuvir (200 mg) and a full dose of daclatasvir (60 mg) daily. The primary endpoint was the proportion of patients with sustained virological responses (SVRs); the other primary outcomes were safety and tolerability. RESULTS Thirty-three patients were enrolled in the study. The median HCV RNA viral load at baseline was 6.8 log10 IU/mL. Twenty-four patients were infected with HCV genotype 2a, seven patients with 1b, and two patients with 2a+1b. All patients achieved a SVR at 12 weeks after the end of treatment. The treatment was well tolerated, and there were no drug-related serious adverse events. CONCLUSION A half dose of sofosbuvir (200 mg once daily) plus a full dose of daclatasvir (60 mg once daily) were suitable for the treatment of acute HCV-infected patients who were undergoing end-stage renal disease and were on haemodialysis.
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Affiliation(s)
- Y L He
- Institution of Hepatology, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China.,Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - S J Yang
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China.,Department of Infectious Diseases, The Eight Hospital of Xi'an, Xi'an, China
| | - C H Hu
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - J Dong
- Department of Haemodialysis, Zhen'An County Hospital, Zhen'An, China
| | - H Gao
- Xi'an Health School, Xi'an City, China
| | - T T Yan
- Institution of Hepatology, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China.,Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - J F Liu
- Institution of Hepatology, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China.,Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Y Yang
- Institution of Hepatology, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - D F Ren
- Institution of Hepatology, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - L Zhu
- Institution of Hepatology, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Y R Zhao
- Institution of Hepatology, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China.,Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - T Y Chen
- Institution of Hepatology, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China.,Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
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7
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Abad S, Vega A, Rincón D, Hernández E, Mérida E, Macías N, Muñoz R, Milla M, Luño J, López-Gómez JM. Effectiveness of direct-acting antivirals in Hepatitis C virus infection in haemodialysis patients. Nefrologia 2017; 37:158-163. [PMID: 27914803 DOI: 10.1016/j.nefroe.2017.04.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Revised: 09/29/2016] [Accepted: 10/02/2016] [Indexed: 01/03/2025] Open
Abstract
Hepatitis C virus (HCV) infection is highly prevalent among patients on haemodialysis and leads to a poorer prognosis compared to patients who do not have said infection. Treatment with interferon and ribavirin is poorly tolerated and there are limited data on the experience with new direct-acting antivirals (DAAs). The aim of this study is to retrospectively analyse the current prevalence of HCV infection and efficacy and safety results with different DAA regimens in the haemodialysis population of 2hospital areas. This is a multicentre, retrospective and observational study in which HCV antibodies were analysed in 465 patients, with positive antibody findings in 54 of them (11.6%). Among these, 29 cases (53.7%) with genotypes 1 and 4 were treated with different DAA regimens, including combinations of paritaprevir/ritonavir, ombitasvir, dasabuvir, sofosbuvir, simeprevir, daclatasvir and ledipasvir, with/without ribavirin. Mean age was 53.3±7.9 years, 72.4% of patients were male and the most important aetiology of chronic kidney disease involved glomerular abnormalities. In 100% of cases, a sustained viral response was achieved after 24 weeks, regardless of DAA regimen received. Adverse effects were not relevant and no case required stopping treatment. In 15 cases, ribavirin was combined with the DAA. In these cases, the most significant adverse effect was anaemic tendency, which was reflected in the increase of the dose of erythropoietin stimulating agents, although none required transfusions. In summary, we conclude that new DAAs for the treatment of HCV in haemodialysis patients are highly effective with minimal adverse effects; it is a very important advance in HCV management. These patients are therefore expected to have a much better prognosis than they have had until very recently.
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Affiliation(s)
- Soraya Abad
- Servicio de Nefrología, Hospital Universitario Gregorio Marañón, Madrid, España
| | - Almudena Vega
- Servicio de Nefrología, Hospital Universitario Gregorio Marañón, Madrid, España
| | - Diego Rincón
- Servicio de Aparato Digestivo, Hospital Universitario Gregorio Marañón, Madrid, España
| | | | | | - Nicolás Macías
- Servicio de Nefrología, Hospital Universitario Gregorio Marañón, Madrid, España
| | - Raquel Muñoz
- Servicio de Medicina del Aparato Digestivo, Hospital 12 de Octubre, Madrid, España
| | - Mónica Milla
- Servicio de Nefrología. Hospital 12 de Octubre, Madrid, España
| | - Jose Luño
- Servicio de Nefrología, Hospital Universitario Gregorio Marañón, Madrid, España
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Abad S, Vega A, Hernández E, Mérida E, de Sequera P, Albalate M, Macías N, Milla M, López-Gómez JM. Universal Sustained Viral Response to the Combination of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with/without Ribavirin in Patients on Hemodialysis Infected with Hepatitis C Virus Genotypes 1 and 4. Am J Nephrol 2017; 45:267-272. [PMID: 28166520 DOI: 10.1159/000454819] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2016] [Accepted: 11/12/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is highly prevalent among patients on hemodialysis (HD) and is associated with poor prognosis. Treatment with interferon and ribavirin is poorly tolerated, and few data are available on the impact of new direct-acting antivirals (DAAs). This study was intended to analyze the efficacy and safety of treatment with a combination of ombitasvir/paritaprevir/ritonavir and dasabuvir with/without ribavirin in HCV-infected patients on HD from 3 hospitals. METHODS This is a multicentric study. We analyze the clinical course of all patients on HD with HCV infection who had been treated with the combination of ombitasvir/paritaprevir/ritonavir and dasabuvir in 3 hospitals in Madrid, Spain. All patients under treatment had undergone Transient elastography (FibroScan®) and HCV RNA (PCR) and HCV genotype were determined simultaneously. RESULTS Thirty-five patients aged 53.3 ± 8.9 years (68.6% males) and with genotypes 1 and 4 were treated with the DAA regimen, and 17 were also given ribavirin. The most common etiology was glomerular disease. Sustained viral response was achieved in 100% of patients. Adverse effects were negligible, and no patient had to discontinue treatment. The most significant side effect was anemia, which led to a significant increase in the dose of erythropoiesis-stimulating agents. Anemia was more marked in patients receiving ribavirin. No patients required transfusions. CONCLUSION A combination of ombitasvir/paritaprevir/ritonavir and dasabuvir with/without ribavirin for the treatment of HCV in patients on HD is highly effective and causes minimal side effects. This regimen represents a major advance in disease management. A considerable improvement in prognosis seems likely.
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Affiliation(s)
- Soraya Abad
- Service of Nephrology, Hospital Universitario Gregorio Marañón, Madrid, Spain
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Patel YA, Muir AJ. Treatment of HCV in Renal Disease: Subtle Management Considerations in the Era of Direct-acting Antivirals. CURRENT HEPATOLOGY REPORTS 2016; 15:285-290. [PMID: 28584732 DOI: 10.1007/s11901-016-0319-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Chronic hepatitis C virus (HCV) infection is burdensome in patients with chronic kidney disease and contributes to substantial liver-related and all-cause morbidity and mortality. HCV infection itself may cause kidney dysfunction, as exemplified through mixed cryoglobulinemic vasculitis. HCV is more prevalent in patients with significant kidney disease compared to the general population, and recent reports have shown inadvertent HCV transmission in U.S. hemodialysis centers. Further, HCV has been demonstrated to accelerate kidney dysfunction and is associated with worse clinical outcomes in patients with kidney disease. As such, the HCV-infected population with concurrent kidney disease is an important patient subgroup that warrants focused medical care and attention. With the advent of direct-acting antivirals (DAAs), the successful treatment of HCV is now a medical reality for many patients. Nuances in regimen selection and timing need to be considered when treating those with kidney dysfunction, particularly for those considering kidney transplantation.
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Affiliation(s)
- Yuval A Patel
- Division of Gastroenterology, Duke University Medical Center, P.O. Box 3913, Durham, NC, 27710
| | - Andrew J Muir
- Division of Gastroenterology, Duke University Medical Center, P.O. Box 3913, Durham, NC, 27710
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10
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Abad S, Vega A, Rincón D, Hernández E, Mérida E, Macías N, Muñoz R, Milla M, Luño J, López-Gómez JM. Effectiveness of direct-acting antivirals in Hepatitis C virus infection in haemodialysis patients. Nefrologia 2016; 37:158-163. [PMID: 27914803 DOI: 10.1016/j.nefro.2016.10.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Revised: 09/29/2016] [Accepted: 10/02/2016] [Indexed: 02/07/2023] Open
Abstract
Hepatitis C virus (HCV) infection is highly prevalent among patients on haemodialysis and leads to a poorer prognosis compared to patients who do not have said infection. Treatment with interferon and ribavirin is poorly tolerated and there are limited data on the experience with new direct-acting antivirals (DAAs). The aim of this study is to retrospectively analyse the current prevalence of HCV infection and efficacy and safety results with different DAA regimens in the haemodialysis population of 2hospital areas. This is a multicentre, retrospective and observational study in which HCV antibodies were analysed in 465 patients, with positive antibody findings in 54 of them (11.6%). Among these, 29 cases (53.7%) with genotypes 1 and 4 were treated with different DAA regimens, including combinations of paritaprevir/ritonavir, ombitasvir, dasabuvir, sofosbuvir, simeprevir, daclatasvir and ledipasvir, with/without ribavirin. Mean age was 53.3±7.9 years, 72.4% of patients were male and the most important aetiology of chronic kidney disease involved glomerular abnormalities. In 100% of cases, a sustained viral response was achieved after 24 weeks, regardless of DAA regimen received. Adverse effects were not relevant and no case required stopping treatment. In 15 cases, ribavirin was combined with the DAA. In these cases, the most significant adverse effect was anaemic tendency, which was reflected in the increase of the dose of erythropoietin stimulating agents, although none required transfusions. In summary, we conclude that new DAAs for the treatment of HCV in haemodialysis patients are highly effective with minimal adverse effects; it is a very important advance in HCV management. These patients are therefore expected to have a much better prognosis than they have had until very recently.
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Affiliation(s)
- Soraya Abad
- Servicio de Nefrología, Hospital Universitario Gregorio Marañón, Madrid, España
| | - Almudena Vega
- Servicio de Nefrología, Hospital Universitario Gregorio Marañón, Madrid, España
| | - Diego Rincón
- Servicio de Aparato Digestivo, Hospital Universitario Gregorio Marañón, Madrid, España
| | | | | | - Nicolás Macías
- Servicio de Nefrología, Hospital Universitario Gregorio Marañón, Madrid, España
| | - Raquel Muñoz
- Servicio de Medicina del Aparato Digestivo, Hospital 12 de Octubre, Madrid, España
| | - Mónica Milla
- Servicio de Nefrología. Hospital 12 de Octubre, Madrid, España
| | - Jose Luño
- Servicio de Nefrología, Hospital Universitario Gregorio Marañón, Madrid, España
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11
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Cacoub P, Desbois AC, Isnard-Bagnis C, Rocatello D, Ferri C. Hepatitis C virus infection and chronic kidney disease: Time for reappraisal. J Hepatol 2016; 65:S82-S94. [PMID: 27641990 DOI: 10.1016/j.jhep.2016.06.011] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2016] [Revised: 06/06/2016] [Accepted: 06/07/2016] [Indexed: 12/18/2022]
Abstract
Hepatitis C virus (HCV) infection is associated with tremendous morbidity and mortality due to liver complications. HCV infection is also associated with many extrahepatic manifestations including cardiovascular diseases, glucose metabolism impairment, cryoglobulinemia vasculitis, B cell non-Hodgkin lymphoma and chronic kidney disease (CKD). Many studies have shown a strong association between HCV and CKD, by reporting (i) an increased prevalence of HCV infection in patients on haemodialysis, (ii) an increased incidence of CKD and proteinuria in HCV-infected patients, and (iii) the development of membranoproliferative glomerulonephritis secondary to HCV-induced cryoglobulinemia vasculitis. HCV seropositivity is found to be associated with an increased relative risk for all-cause and cardiovascular mortality in the dialysis population. HCV seropositivity is linked to lower patient and graft survival after kidney transplantation. Such poor HCV-associated prognosis should have encouraged clinicians to treat HCV in CKD patients. However, due to frequent side effects and the poor efficacy of interferon-based treatments, very few HCV dialysis patients have received HCV medications until now. The emergence of new direct acting, interferon-free antiviral treatment, leading to HCV cure in most cases with a satisfactory safety profile, will shortly modify the management of HCV infection in CKD patients. In patients with a glomerular filtration rate (GFR) >30ml/min, the choice of DAA is not restricted. In those with a GFR <30 and >15ml/min, only paritaprevir/ritonavir/ombitasvir/dasabuvir or a grazoprevir plus elbasvir regimen are approved. In patients with end stage renal disease (GFR <15ml/min or dialysis), current data only allows for the use of a grazoprevir plus elbasvir combination. No doubt these data will be modified in the future with the advent of new studies including larger cohorts of HCV patients with renal impairment.
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Affiliation(s)
- Patrice Cacoub
- Sorbonne Universités, UPMC Université Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), F-75005 Paris, France; INSERM, UMR_S 959, F-75013 Paris, France; CNRS, FRE3632, F-75005 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, F-75013 Paris, France.
| | - Anne Claire Desbois
- Sorbonne Universités, UPMC Université Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), F-75005 Paris, France; INSERM, UMR_S 959, F-75013 Paris, France; CNRS, FRE3632, F-75005 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, F-75013 Paris, France
| | - Corinne Isnard-Bagnis
- Sorbonne Universités, UPMC Université Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), F-75005 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Nephrology, F-75013 Paris, France
| | - Dario Rocatello
- Center of Research of Immunopathology and Rare Diseases, and Nephrology and Dialysis Unit. San G. Bosco Hospital and University of Turin, Italy
| | - Clodoveo Ferri
- Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, 41124 Modena, Italy
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Agarwal SK, Bhowmik D, Mahajan S, Bagchi S. Pegylated interferon monotherapy for hepatitis C virus infection in patients on hemodialysis: A single center study. Indian J Nephrol 2016; 26:244-51. [PMID: 27512295 PMCID: PMC4964683 DOI: 10.4103/0971-4065.172228] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
There is no published study from India on hepatitis C virus (HCV) treatment in dialysis patients. Patients on dialysis with HCV infection treated with pegylated interferon (Peg-INF) monotherapy were studied. All patients were subjected to HCV-polymerase chain reaction, viral load, genotype, and liver biopsy. Quantitative HCV-RNA was performed monthly. Patients with genotype 1 and 4 were given 12 month therapy while those with genotypes 2 and 3 were given 6 months therapy. Response was classified as per standard criteria of rapid virological response (RVR), early virological response (EVR), end of treatment response (ETR), and sustained virological response (SVR). A total of 85 patients were treated. Mean age was 35.2 ± 10.5 (range 15-67) years, and 77.6% were males. HCV genotypes were 1 in 40.9%, 2 in 12%, 3 in 36.1%, 4 in 3.6%, and others in 7.2%. Mean viral load was 10(6) copies/mL. Mean liver biopsy grade was 4 ± 1.7 and stage 0.8 ± 0.8. Mean time from diagnosis of HCV infection and the treatment start was 10.7 ± 14.3 months. One patient died of unrelated illness, one was lost to follow-up, and three could not sustain treatment due to cost. Forty-three of the 80 (54%) patients had RVR while 49 (61%) patients had EVR and ETR. There was no difference in term of RVR related to genotype. Fifty -four percentage had SVR. Mild flu-like symptoms were seen in all patients. Sixty-four (80%) patients required increase in erythropoietin doses. Twenty-eight (35%) patients developed leukopenia (three treatment-limiting) and 16 (20%) developed thrombocytopenia (one treatment-limiting). Five patients developed tuberculosis, five bacterial pneumonia, and one bacterial knee monoarthritis. None of the patients developed depression. Our study concludes that Peg-INF monotherapy resulted in 54% RVR and SVR in dialysis patients with HCV infection. Therapy was well-tolerated with minimal side effects. There was no effect of viral genotype on response to therapy.
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Affiliation(s)
- S K Agarwal
- Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
| | - D Bhowmik
- Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
| | - S Mahajan
- Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
| | - S Bagchi
- Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
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Hepatitis C virus infection in nonliver solid organ transplant candidates and recipients. Curr Opin Organ Transplant 2015; 20:259-66. [PMID: 25944237 DOI: 10.1097/mot.0000000000000195] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
PURPOSE OF REVIEW Transplantation is the best treatment for many patients with end-stage organ failure. Hepatitis C infection is prevalent among solid organ candidates and recipients and continues to represent a major source of morbidity and mortality. Prior interferon (IFN)-based therapies have been associated with limited efficacy and high rates of adverse events. Furthermore, prior IFN-based regimens are associated with high rates of allograft rejection limiting their use post-transplant. This review will outline the limited experience with current treatment regimens and how to incorporate the new hepatitis C virus (HCV) treatment regimens. RECENT FINDINGS The introduction of new direct-acting antiviral (DAA) agents against HCV has dramatically altered the landscape of treatment for HCV. Different all-oral regimens are currently available and are rapidly becoming the standard for treating patients with chronic hepatitis C. Excluding patients with liver disease or those who received liver transplant, those regimens have not been studied in patients awaiting solid organ transplant, or those transplanted. SUMMARY The safety and efficacy of DAAs in patients awaiting liver transplant and liver transplant recipients provide us with some insight and guidance on how to use those all-oral IFN-free regimens to allow effective treatment for patients who received or are awaiting nonliver solid organ transplants.
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Hundemer GL, Sise ME, Wisocky J, Ufere N, Friedman LS, Corey KE, Chung RT. Use of sofosbuvir-based direct-acting antiviral therapy for hepatitis C viral infection in patients with severe renal insufficiency. Infect Dis (Lond) 2015; 47:924-9. [PMID: 26365684 PMCID: PMC4732277 DOI: 10.3109/23744235.2015.1078908] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Sofosbuvir-based direct-acting antiviral therapy revolutionized the treatment of hepatitis C virus (HCV) infection. However, sofosbuvir use is not approved for patients with severe renal insufficiency (estimated glomerular filtration (eGFR) rate below 30 ml/min) or end-stage renal disease (ESRD) based on concerns raised during premarket animal testing over hepatobiliary and cardiovascular toxicity in this population. We report the first published data on use of sofosbuvir-based regimens in patients with severe renal insufficiency and ESRD, focusing on clinical efficacy and safety. Six patients were treated with full dose sofosbuvir; three received sofosbuvir and simeprevir, two received sofosbuvir and ribavirin, and one received sofosbuvir, ribavirin, and interferon. Three of the patients had cirrhosis. On-treatment viral suppression was 100% and sustained virological response (SVR) rate at 12 weeks was 67%. One patient had to discontinue antiviral therapy early due to side effects. No hepatobiliary or cardiovascular toxicity was reported.
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Affiliation(s)
- Gregory L. Hundemer
- Department of Medicine, Massachusetts General Hospital
- Department of Medicine, Harvard Medical School
| | - Meghan E. Sise
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital
- Department of Medicine, Harvard Medical School
| | - Jessica Wisocky
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital
- Department of Medicine, Harvard Medical School
| | - Nneka Ufere
- Department of Medicine, Massachusetts General Hospital
- Department of Medicine, Harvard Medical School
| | - Lawrence S. Friedman
- Department of Medicine, Newton-Wellesley Hospital
- Department of Medicine, Harvard Medical School
- Department of Medicine, Tufts University School of Medicine
| | - Kathleen E. Corey
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital
- Department of Medicine, Harvard Medical School
| | - Raymond T. Chung
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital
- Department of Medicine, Harvard Medical School
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15
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Fabrizi F, Dixit V, Messa P, Martin P. Pegylated Interferon Mono-Therapy of Chronic Hepatitis C in the Dialysis Population: Systematic Review and Meta-Analysis. Ther Apher Dial 2015. [PMID: 26197927 DOI: 10.1111/1744-9987.12318] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
The medical literature on mono-therapy with pegylated interferon for chronic hepatitis C in dialysis patients is mostly based on small clinical studies and the efficacy and safety of such approach is still unclear. A systematic review of the literature with a meta-analysis of clinical studies was performed in order to evaluate the efficacy and safety of mono-therapy with pegylated interferon of chronic hepatitis C in patients on regular dialysis. The primary outcome was sustained viral response (as a measure of efficacy); the secondary outcome was drop-out rate (as a measure of tolerability). The random-effects model of Der Simonian and Laird was used, with heterogeneity and sensitivity analyses. Twenty-four clinical studies (N = 744 unique patients) were retrieved; five (21%) being randomized controlled trials. The summary estimate for sustained viral response and drop-out rate was 0.40 (95% confidence interval [CI], 0.35; 0.46) and 0.14 (95% CI, 0.09; 0.20), respectively. The most frequent side-effects requiring discontinuation of treatment were hematological (31/83 = 37%) and gastrointestinal (9/31 = 10.8%). Meta-regression analysis showed a detrimental role of ageing on the frequency of sustained virological response (P = 0.01); drop-out rate was greater in diabetics (P < 0.005). Important heterogeneity was seen with regard to drop-out rate only. In summary, pegylated interferon monotherapy of hepatitis C in dialysis patients resulted unsatisfactory in terms of efficacy and safety. Studies with novel direct-acting antiviral agents in combination with pegylated interferon and ribavirin for the treatment of hepatitis C virus in dialysis population are under way.
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Affiliation(s)
- Fabrizio Fabrizi
- Division of Nephrology and Dialysis, Maggiore Hospital and IRCCS Foundation, Milano, Italy
| | - Vivek Dixit
- Division of Hepatology, University School of Medicine, Miami, FL, USA
| | - Piergiorgio Messa
- Division of Nephrology and Dialysis, Maggiore Hospital and IRCCS Foundation, Milano, Italy
| | - Paul Martin
- Division of Hepatology, University School of Medicine, Miami, FL, USA
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Rostaing L, Alric L, Izopet J, Kamar N. What are the management issues for hepatitis C in dialysis patients?: hepatitis C virus infection and its treatment in patients with end-stage renal disease. Semin Dial 2015; 27:451-5. [PMID: 25204878 DOI: 10.1111/sdi.12290] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Affiliation(s)
- Lionel Rostaing
- Department of Nephrology, and Organ Transplantation, CHU Rangueil, Toulouse, France; INSERM U563, /IFR-BMT, Toulouse, France, IFR-BMT, CHU Purpan, Toulouse, France; Université Paul Sabatier, Toulouse, France
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Zimner-Rapuch S, Janus N, Deray G, Launay-Vacher V. New therapies for hepatitis C: considerations in patients with renal impairment. Drugs 2015; 74:1307-13. [PMID: 25060981 DOI: 10.1007/s40265-014-0268-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Hepatitis C virus (HCV) is a major public health issue because infection may lead to liver failure, cirrhosis and hepatocellular carcinoma. In patients with renal dysfunction, hepatitis C can also worsen the underlying renal disease. Treating HCV infection is thus mandatory in this population. New therapies for hepatitis C have recently been developed, and some have been launched. Most of them are used in combination with the current standard of care, ribavirin and pegylated interferon alfa. Some of them can be used in regimens without ribavirin and/or pegylated interferon. However, few data are available on dosage adjustment for renal function in patients receiving these very new drugs. We reviewed the literature on this subject and gathered information, although scarce, to propose guidelines for using these drugs in patients with chronic kidney disease.
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Affiliation(s)
- Sarah Zimner-Rapuch
- Service ICAR, Service de Néphrologie, Groupe Hospitalier Pitié-Salpêtrière, 47-83 Boulevard de l'Hôpital, 75013, Paris, France,
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18
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Sperl J, Frankova S, Senkerikova R, Neroldova M, Hejda V, Volfova M, Merta D, Viklicky O, Spicak J, Jirsa M. Relevance of low viral load in haemodialysed patients with chronic hepatitis C virus infection. World J Gastroenterol 2015; 21:5496-504. [PMID: 25987772 PMCID: PMC4427671 DOI: 10.3748/wjg.v21.i18.5496] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2014] [Revised: 01/19/2015] [Accepted: 02/11/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To identify predictors of sustained virological response in hemodialysed patients treated by PEGinterferon α for chronic hepatitis C, genotype 1. METHODS The sustained virological response (SVR) rate, IL28B genotype, IFNL4 genotype, initial viral load (IVL) and other pretreatment variables in 39 end-stage renal disease patients (ESRD) on maintenance haemodialysis (HD) infected with hepatitis C virus (HCV), genotype 1b, were compared with a control group of 109 patients with normal kidney function treated within the same period. All the patients were treatment naïve and had well compensated liver disease. The ESRD patients received 135 μg of PEGylated interferon α-2a (PegIFN-α) weekly and a reduced dose of ribavirin (RBV) was administered to 23/39 patients with an initial haemoglobin level > 10 g/dL. Control group patients were given standard doses of PegIFN-α and RBV. SVR was assessed as HCV RNA negativity 24 wk post-treatment. A t-test or ANOVA were used for comparisons of the means and a χ(2) test compared the frequencies. Logistic regression was used to determine significant predictors of SVR. Cutoff values for continuous variables were obtained from Receiver Operating Characteristic analysis. RESULTS The distribution of IL28B rs12979860 CC, CT and TT genotypes in the ESRD group was 28.2%, 64.1% and 7.7%, respectively, and 19.3%, 62.4% and 18.3% in the controls. The IFNL4 genotype was in almost absolute linkage disequlibrium with IL28B. The proportion of patients with a low IVL (< 600000 IU/mL) was significantly higher in the ESRD group than in the controls (28/39, 71.8% vs 51/109, 46.8%, P = 0.009), as was the proportion of patients with low IVL in IL28B CC carriers compared with non-CC carriers in the ESRD group (10/11, 90.9% vs 18/28, 64.3%, P = 0.0035). This difference was not found in the controls (7/22, 31.8% vs 44/87, 50.6%, P = 0.9). The overall SVR rate was 64.1% (25/39) in the ESRD group and 50.5% (55/109) in the control group (P = 0.19). 11/11 (100%) and 19/22 (86.4%) IL28B CC patients achieved SVR in the ESRD and control groups, respectively. A statistically significant association between SVR and IL28B and IFNL4 variants was found in both groups. The ESRD patients who achieved SVR showed the lowest IVL [median 21000, interquartile range (IQR): 6000-23000 IU/mL], compared with ESRD individuals without SVR (1680000, IQR: 481000-6880000, P = 0.001), controls with SVR (387000, IQR: 111000-1253000) and controls without SVR (905000, IQR: 451000-3020000). In ESRD, an IVL < 600000 IU/mL was strongly associated with SVR: 24/28 (85.7%) patients who achieved SVR had viraemia below this threshold. CONCLUSION Haemodialysis decreases the viral load, especially in IL28B CC genotype carriers. A low IVL was the strongest predictor of SVR in ESRD patients identified in multivariate analysis.
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20
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Viral hepatitis C therapy: pharmacokinetic and pharmacodynamic considerations. Clin Pharmacokinet 2014; 53:409-27. [PMID: 24723109 DOI: 10.1007/s40262-014-0142-5] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Chronic hepatitis C is a global health problem. To prevent or reduce complications, the hepatitis C virus (HCV) infection needs to be eradicated. There have been several developments in treating these patients since the discovery of the virus. As of 1 January 2014, the drugs that are approved for treatment of chronic HCV infection are peginterferon-α, ribavirin, boceprevir, telaprevir, simeprevir and sofosbuvir. In this review we provide an overview of the clinical pharmacokinetic characteristics of these agents by describing their absorption, distribution, metabolism and excretion. In the pharmacodynamic part we summarize what is known about the relationships between the pharmacokinetics of each drug and efficacy or toxicity. We briefly discuss the pharmacokinetics and pharmacodynamics of chronic hepatitis C treatment in special patient populations, such as patients with liver cirrhosis, renal insufficiency or HCV/HIV coinfection, and children. With this knowledge, physicians, pharmacists, nurse practitioners, etc. should be educated to safely and effectively treat HCV-infected patients.
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21
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Fabrizi F, Dixit V, Messa P, Martin P. Antiviral therapy (pegylated interferon and ribavirin) of hepatitis C in dialysis patients: meta-analysis of clinical studies. J Viral Hepat 2014; 21:681-9. [PMID: 25040244 DOI: 10.1111/jvh.12276] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2014] [Accepted: 03/04/2014] [Indexed: 12/13/2022]
Abstract
Information on the antiviral treatment (pegylated interferon plus ribavirin) of chronic infection by hepatitis C virus (HCV) in patients on long-term dialysis is extremely limited. We evaluated the efficacy and safety of combination antiviral therapy (pegylated interferon plus ribavirin) in patients on long-term dialysis with chronic hepatitis C by performing a systematic review of the literature with a meta-analysis of clinical studies. The primary outcome was sustained virological response (SVR) (as a measure of efficacy); the secondary outcome was dropout rate (as a measure of tolerability). We used the random-effects model of DerSimonian and Laird, with heterogeneity and sensitivity analyses. We identified eleven clinical studies (287 unique patients), two of them being controlled clinical trials. The summary estimate for SVR and dropout rate was 0.60 (95% Confidence Intervals, 0.47; 0.71) and 0.18 (95% CI, 0.08; 0.35), respectively; studies being heterogeneous with regard to both the outcomes. Stratified analysis reported a higher SVR rate in controlled trials, 0.86 (95% CI, 0.27; 0.99). The most common sources of dropout were anaemia (11/46 = 23%) and infections (6/46 = 13%). Meta-regression analysis showed a detrimental impact of HCV genotype 1 (P = 0.036) and dropout (P = 0.0001) rate upon the frequency of SVR. Antiviral therapy based on pegylated interferon plus ribavirin for HCV gives encouraging results in terms of efficacy and safety among patients on long-term dialysis; such approach should be considered the current standard of care for HCV-infected individuals on regular dialysis.
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Affiliation(s)
- F Fabrizi
- Division of Nephrology, Maggiore Hospital, IRCCS Foundation, Milano, Italy; Division of Hepatology, School of Medicine, University of Miami, Miami, FL, USA
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Burra P, Rodríguez-Castro KI, Marchini F, Bonfante L, Furian L, Ferrarese A, Zanetto A, Germani G, Russo FP, Senzolo M. Hepatitis C virus infection in end-stage renal disease and kidney transplantation. Transpl Int 2014; 27:877-91. [PMID: 24853721 DOI: 10.1111/tri.12360] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Revised: 04/02/2014] [Accepted: 05/12/2014] [Indexed: 12/18/2022]
Abstract
Liver disease secondary to chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in patients with end-stage renal disease (ESRD) on renal replacement therapy and after kidney transplantation (KT). Hemodialytic treatment (HD) for ESRD constitutes a risk factor for bloodborne infections because of prolonged vascular access and the potential for exposure to infected patients and contaminated equipment. Evaluation of HCV-positive/ESRD and HCV-positive/KT patients is warranted to determine the stage of disease and the appropriateness of antiviral therapy, despite such treatment is challenging especially due to tolerability issues. Antiviral treatment with interferon (IFN) is contraindicated after transplantation due to the risk of rejection, and therefore, treatment is recommended before KT. Newer treatment strategies of direct-acting antiviral agents in combination are revolutionizing HCV therapy, as a result of encouraging outcomes streaming from recent studies which report increased sustained viral response, low or no resistance, and good safety profiles, including preservation of renal function. KT has been demonstrated to yield better outcomes with respect to remaining on HD although survival after KT is penalized by the presence of HCV infection with respect to HCV-negative transplant recipients. Therefore, an appropriate, comprehensive, easily applicable set of clinical practice management guidelines is necessary in both ESRD and KT patients with HCV infection and HCV-related liver disease.
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Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
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Pipili C, Cholongitas E. Μanagement of patients with hepatitis B and C before and after liver and kidney transplantation. World J Hepatol 2014; 6:315-25. [PMID: 24868325 PMCID: PMC4033289 DOI: 10.4254/wjh.v6.i5.315] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Revised: 03/10/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
New nucleos(t)ide analogues (NAs) with high genetic barrier to hepatitis B virus (HBV) resistance (such as entecavir, tenofovir) have improved the prognosis of patients with HBV decompensated cirrhosis and have prevented HBV recurrence after liver transplantation (LT). NAs are considered the most proper approach for HBV infection in patients under renal replacement therapy but their doses should be adjusted according to the patient's creatinine clearance. In addition, physicians should be aware of the potential nephrotoxicity. However, patients with chronic hepatitis C and decompensated cirrhosis can receive only one therapeutic option before LT, as well as for Hepatitis C virus (HCV) recurrence after LT, which is the combination of subcutaneous Peg-IFN and ribavirin. Generally, therapy for HCV after renal transplantation should be avoided. Although the optimal antiviral therapy for HCV infection has not been established, attention has turned to a new, oral direct acting antiviral treatment which marks a promising strategy in prognosis and in amelioration of these diseases.
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Affiliation(s)
- Chrysoula Pipili
- Chrysoula Pipili, Department of Nephrology, Laiki Merimna, 17343 Athens, Greece
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Liu CH, Kao JH. Nanomedicines in the treatment of hepatitis C virus infection in Asian patients: optimizing use of peginterferon alfa. Int J Nanomedicine 2014; 9:2051-67. [PMID: 24812506 PMCID: PMC4008289 DOI: 10.2147/ijn.s41822] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Asia is endemic for hepatitis C virus (HCV) infection, which is the leading cause of cirrhosis, hepatic decompensation, hepatocellular carcinoma, and liver transplantation worldwide. HCV has six major genotypes and each HCV genotype has its specific geographic distribution. HCV genotypes 1, 2, 3, and 6 are common in Asia. The aim of HCV treatment is to eradicate the virus by effective therapeutic agents; viral clearance is durable after long-term post-treatment follow-up. In most Asian countries, peginterferon alfa (PEG-IFN α) in combination with ribavirin remains the standard of care, and the overall sustained viral response (SVR) rate in Asian HCV patients is higher than that in Western patients. The differences are most significant in patients with HCV genotype 1 (HCV-1) infection, which is attributed to the higher frequency of IFN-responsive or favorable interleukin-28B (IL-28B) genotype in Asian populations than in other ethnic populations. In addition, the introduction of response-guided therapy, where the optimized treatment duration is based on the early viral kinetics during the first 12 weeks of treatment, increases the SVR rate. Recently, telaprevir or boceprevir-based triple therapy was found to further improve the SVR rate in treated and untreated HCV-1 patients and has become the new standard of care in Western and some Asian countries. Many novel direct-acting antiviral agents, either in combination with PEG-IFN α plus ribavirin or used as IFN-free regimens are under active investigation. At the time of this writing, simeprevir and sofosbuvir have been approved in the US. Because the SVR rates in Asian HCV patients receiving PEG-IFN α plus ribavirin therapy are high, health care providers should judiciously determine the clinical usefulness of these novel agents on the basis of treatment duration, anticipated viral responses, patient tolerance, financial burdens, and drug accessibility.
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Affiliation(s)
- Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan ; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan ; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan ; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan ; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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25
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Sherman RA. Briefly Noted. Semin Dial 2014. [DOI: 10.1111/sdi.12176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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