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Driedger M, Galanakis C, Cooper C. Direct acting antiviral HCV treatment does not influence renal function. Medicine (Baltimore) 2020; 99:e20436. [PMID: 32481445 DOI: 10.1097/md.0000000000020436] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
HCV infection is associated with chronic kidney disease due to several mechanisms. Patients treated with interferon-based regimens demonstrate improved renal function and reduced incidence of chronic kidney disease. There is scarce evidence on the effect of direct acting antiviral regimens (DAAs) on renal function.We evaluated serial measures of renal function in a cohort of HCV-infected participants following completion of DAA-based treatment regimens.Measures of glomerular filtration rate (GFR) were estimated by the CKD-EPI equation. Data was recorded at end of treatment, and at 6-12 months, 12-24 months, and greater than 24 months following treatment completion. Group-based trajectory modeling was used to determine distinct GFR trajectories. Predictors of group membership were determined by multinomial regression analysis.Six trajectories were identified. One trajectory comprising 27% of the cohort demonstrated declining renal function and the others demonstrated no change in renal function over time. Baseline GFR did not predict SVR. Diabetes was associated with lower post-treatment GFR but patients with diabetes did not demonstrate a decrease in GFR over the period of evaluation. Cirrhosis and SVR were not significant predictors of GFR or GFR trajectory.There is no clinically relevant change in renal function among the majority of HCV-infected patients following completion of DAA-based treatments. Renal function does not influence the efficacy of DAA-based regimens. No consistent effect of DAA treatment and/or SVR on renal function was observed over a 2-year period following treatment completion.
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Constancio NS, Ferraz MLG, Martins CTB, Kraychete AC, Bitencourt PL, Nascimento MMD. Hepatitis C in Hemodialysis Units: diagnosis and therapeutic approach. ACTA ACUST UNITED AC 2020; 41:539-549. [PMID: 30806444 PMCID: PMC6979573 DOI: 10.1590/2175-8239-jbn-2018-0177] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Accepted: 11/28/2018] [Indexed: 12/13/2022]
Abstract
According to data from the last census of the Brazilian Society of Nephrology (SBN), the prevalence of hepatitis C virus (HCV) in Brazilian hemodialysis units (HU) is 3.3%, about three times higher than what is reported for the Brazilian general population. Often, professionals working in HU are faced with clinical situations that require rapid HCV diagnosis in order to avoid horizontal transmission within the units. On the other hand, thanks to the development of new antiviral drugs, the cure of patients with HCV, both in the general population and in patients with chronic kidney disease and the disease eradication, appear to be very feasible objectives to be achieved in the near future . In this scenario, SBN and the Brazilian Society of Hepatology present in this review article a proposal to approach HCV within HUs.
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Affiliation(s)
- Natasha Silva Constancio
- Associação Renal Vida Rio do Sul, Rio do Sul, SC, Brasil.,Sociedade Brasileira de Nefrologia, São Paulo, SP, Brasil
| | - Maria Lucia Gomes Ferraz
- Universidade Federal de São Paulo, São Paulo, SP, Brasil.,Sociedade Brasileira de Hepatologia, São Paulo, SP, Brasil
| | | | | | | | - Marcelo Mazza do Nascimento
- Universidade Federal do Paraná, Curitiba, PR, Brasil.,Sociedade Brasileira de Nefrologia, São Paulo, SP, Brasil
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Torun D, Soydas B, Tekkarismaz N, Ozelsancak R, Micozkadioglu H, Haberal M. Experience with antiviral agents for treatment of hepatitis C virus infection in hemodialysis patients on the kidney wait list. Hemodial Int 2019; 23:E78-E82. [PMID: 30762283 DOI: 10.1111/hdi.12719] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 10/18/2018] [Accepted: 10/18/2018] [Indexed: 01/26/2023]
Abstract
INTRODUCTION Hepatitis C virus (HCV) infection is associated with increased mortality and morbidity in kidney transplant patients. The ability to establish a sustained viral response before renal transplant is important for these patients. Direct-acting antiviral agents can increase the sustained viral response in most patients with HCV infection. In this case series, we aimed to determine the efficacy and safety of a combined therapy of ombitasvir, paritaprevir, ritonavir, and dasabuvir with or without ribavirin in patients with HCV genotype 1 infection without cirrhosis and on hemodialysis who were awaiting deceased-donor kidney transplant. METHODS Our study included eight male and two female HCV ribonucleic acid (RNA)-positive hemodialysis patients (mean age 50.7 ± 15 years, mean hemodialysis duration 14 ± 5.5 years, mean HCV duration 18 ± 3.7 years). FINDINGS Three patients with genotype 1a received oral therapy with 12.5 mg ombitasvir, 150 mg paritaprevir, 7 5 mg ritonavir, and 250 mg dasabuvir plus 200 mg ribavirin for 12 weeks. Seven patients with genotype 1b received 12.5 mg ombitasvir, 150 mg paritaprevir, 75 mg ritonavir, and 250 mg dasabuvir without ribavirin treatment for 12 weeks. The sustained virologic response rate was 100% at 12 weeks after completion of antiviral treatment in both treatment groups. No serious adverse effects were observed in either treatment group. Five patients had constitutional symptoms such as nausea, anorexia, and fatigue. During the treatment period, hemoglobin, white cell blood count, thrombocyte, and ferritin levels were similar to pretreatment levels. Treatment did not affect weekly erythropoietin and monthly intravenous iron treatment doses. DISCUSSION Direct-acting antiviral agents are safe and effective for generating a sustained viral response in HCV genotype 1-infected hemodialysis patients on kidney wait lists.
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Affiliation(s)
- Dilek Torun
- Department of Nephrology, Adana Dr Turgut Noyan Research and Medical Center, Baskent University Faculty of Medicine, Adana, Turkey
| | - Baris Soydas
- Department of Gastroenterology, Adana Dr Turgut Noyan Research and Medical Center, Baskent University Faculty of Medicine, Adana, Turkey
| | - Nihan Tekkarismaz
- Department of Nephrology, Adana Dr Turgut Noyan Research and Medical Center, Baskent University Faculty of Medicine, Adana, Turkey
| | - Ruya Ozelsancak
- Department of Nephrology, Adana Dr Turgut Noyan Research and Medical Center, Baskent University Faculty of Medicine, Adana, Turkey
| | - Hasan Micozkadioglu
- Department of Nephrology, Adana Dr Turgut Noyan Research and Medical Center, Baskent University Faculty of Medicine, Adana, Turkey
| | - Mehmet Haberal
- Department of Transplantation and General Surgery, Baskent University Faculty of Medicine, Adana, Turkey
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Lawitz E, Gane E, Cohen E, Vierling J, Agarwal K, Hassanein T, Mantry PS, Pockros PJ, Bennett M, Kemmer N, Morelli G, Zha J, Wang D, Shulman NS, Cohen DE, Reddy KR. Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir in Patients With Hepatitis C Virus Genotype 1 or 4 Infection and Advanced Kidney Disease. Kidney Int Rep 2019; 4:257-266. [PMID: 30775622 PMCID: PMC6365406 DOI: 10.1016/j.ekir.2018.10.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Accepted: 10/01/2018] [Indexed: 02/08/2023] Open
Abstract
INTRODUCTION Hepatitis C virus (HCV) infection is common in patients with end-stage renal disease. We investigated the safety and efficacy of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) ± dasabuvir (DSV) ± ribavirin (RBV) in 2 phase 3, open-label, multicenter studies in patients with stage 4 or 5 chronic kidney disease (CKD). METHODS RUBY-I, Cohort 2 enrolled treatment-naïve or -experienced patients with HCV genotype (GT) 1a or 1b infection, with or without cirrhosis. Patients received 12 weeks (24 weeks for GT1a patients with cirrhosis) of OBV/PTV/r + DSV; all GT1a patients received RBV. RUBY-II enrolled treatment-naïve patients with GT1a or GT4 infection without cirrhosis. All patients received 12 weeks of RBV-free treatment: OBV/PTV/r + DSV for GT1a-infected patients; OBV/PTV/r for GT4-infected patients. The primary endpoint was sustained virologic response at posttreatment week 12 (SVR12). RESULTS RUBY-I, Cohort 2 and RUBY-II enrolled 66 patients, including 50 (76%) on dialysis; 15 (23%) had compensated cirrhosis. Overall, the SVR12 rate was 95% (63/66); 1 patient had virologic failure. There were 3 discontinuations due to adverse events. Seventy-three percent (27/37) of patients receiving RBV had adverse events leading to RBV dose modification. The RBV-free RUBY-II study had no hemoglobin-associated adverse events. CONCLUSION Treatment with OBV/PTV/r ± DSV ± RBV was well tolerated and patients with HCV GT1 or 4 infection and stage 4 or 5 CKD had high SVR12 rates, including patients with compensated cirrhosis and/or prior treatment experience.
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Affiliation(s)
- Eric Lawitz
- The Texas Liver Institute, University of Texas Health, San Antonio, Texas, USA
| | - Edward Gane
- Auckland City Hospital, Auckland, New Zealand
| | - Eric Cohen
- AbbVie Inc., North Chicago, Illinois, USA
| | | | - Kosh Agarwal
- Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London, UK
| | - Tarek Hassanein
- Southern California GI and Liver Centers and Southern California Research Center, Coronado, California, USA
| | | | | | - Michael Bennett
- Medical Associates Research Group, San Diego, California, USA
| | | | - Giuseppe Morelli
- University of Florida Health Science Center, Gainesville, Florida, USA
| | | | - Deli Wang
- AbbVie Inc., North Chicago, Illinois, USA
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Shuster DL, Menon RM, Ding B, Khatri A, Li H, Cohen E, Jewett M, Cohen DE, Zha J. Effects of chronic kidney disease stage 4, end-stage renal disease, or dialysis on the plasma concentrations of ombitasvir, paritaprevir, ritonavir, and dasabuvir in patients with chronic HCV infection: pharmacokinetic analysis of the phase 3 RUBY-I and RUBY-II trials. Eur J Clin Pharmacol 2018; 75:207-216. [PMID: 30291369 DOI: 10.1007/s00228-018-2566-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Accepted: 09/25/2018] [Indexed: 01/20/2023]
Abstract
PURPOSE To characterize the pharmacokinetics of ombitasvir, paritaprevir, ritonavir, dasabuvir, and ribavirin in hepatitis C virus (HCV)-infected patients with chronic kidney disease stage 4 (CKD4) or end-stage renal disease (ESRD), including those on dialysis, in the open-label phase 3 RUBY-I and RUBY-II studies. METHODS Patients (n = 18 CKD4, n = 68 ESRD) received ombitasvir/paritaprevir/ritonavir 25/150/100 mg once daily ± dasabuvir 250 mg twice daily ± ribavirin 200 mg once daily for 12 or 24 weeks. Intensive pharmacokinetic samples were collected from ten patients; sparse samples were collected from all patients. Arterial and venous samples were collected from three patients during hemodialysis. Area under the plasma concentration-time curve (AUC) was estimated using noncompartmental analyses for intensive data, and steady-state trough concentrations (Ctrough) were obtained from the sparse data. Pharmacokinetic results from RUBY-I and RUBY-II were compared empirically to historical data. RESULTS The AUC values of ombitasvir, paritaprevir, ritonavir, and dasabuvir were comparable between CKD4 and ESRD patients and were within the range of values observed in historical studies; dialysis had no effect on drug exposures. Ribavirin was extracted during hemodialysis but had similar exposures on dialysis and non-dialysis days. Individual steady-state Ctrough values for each drug overlapped between CKD4 and ESRD patients, and values in both groups were similar to historical values. CONCLUSION Plasma concentrations of ombitasvir, paritaprevir, ritonavir, and dasabuvir were not altered by renal impairment or dialysis, suggesting these agents can be administered to HCV-infected CKD4 or ESRD patients, including those on dialysis, without dose adjustment. TRIAL REGISTRATION Clinicaltrials.gov identifiers: NCT02207088 (RUBY-I) and NCT02487199 (RUBY-II).
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Affiliation(s)
- Diana L Shuster
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA
| | - Rajeev M Menon
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA
| | - Bifeng Ding
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA
| | - Amit Khatri
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA
| | - Hong Li
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA
| | - Eric Cohen
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA
| | - Melissa Jewett
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA
| | - Daniel E Cohen
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA
| | - Jiuhong Zha
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA.
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Menon RM, Polepally AR, Khatri A, Awni WM, Dutta S. Clinical Pharmacokinetics of Paritaprevir. Clin Pharmacokinet 2018; 56:1125-1137. [PMID: 28236252 DOI: 10.1007/s40262-017-0520-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Paritaprevir is a potent hepatitis C virus (HCV) nonstructural (NS) protein 3/4A protease inhibitor that is used in combination with other direct-acting antivirals (DAAs) for the treatment of chronic HCV infection. Paritaprevir is primarily metabolized by cytochrome P450 (CYP) 3A4 and is administered with a low dose of ritonavir to achieve drug concentrations suitable for once-daily dosing. Coadministration of paritaprevir with ritonavir increases the half-life of single-dose paritaprevir from approximately 3 h to 5-8 h, doubles the time to maximum plasma concentration (T max) from 2.3 to 4.7 h, and increases exposures 30-fold for maximum observed plasma concentration (C max), 50-fold for area under the plasma concentration-time curve (AUC), and >300-fold for trough concentration (C 24). Paritaprevir displays highly variable, nonlinear pharmacokinetics, with C max and AUC increasing in a greater than dose proportional manner when administered with or without ritonavir. In the presence of ritonavir, paritaprevir is excreted mostly unchanged in feces via biliary excretion. Paritaprevir exposures are higher in Japanese subjects compared with Caucasian subjects; however, no dose adjustment is needed for Japanese patients as the higher exposures are safe and well tolerated. The pharmacokinetic characteristics of paritaprevir are similar between healthy subjects and HCV-infected patients, and are not appreciably altered by mild or moderate hepatic impairment or mild, moderate, or severe renal impairment, including those on dialysis. Paritaprevir exposures are increased in patients with severe hepatic impairment. Although the presence of a low dose of ritonavir in paritaprevir-containing regimens increases the likelihood of drug-drug interactions, results from several drug interaction studies demonstrated that paritaprevir-containing regimens can be coadministered with many comedications that are commonly prescribed in HCV-infected patients.
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Affiliation(s)
- Rajeev M Menon
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Dept. R4PK, Bldg. AP31-3, 1 North Waukegan Road, North Chicago, IL, 60064, USA.
| | - Akshanth R Polepally
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Dept. R4PK, Bldg. AP31-3, 1 North Waukegan Road, North Chicago, IL, 60064, USA
| | - Amit Khatri
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Dept. R4PK, Bldg. AP31-3, 1 North Waukegan Road, North Chicago, IL, 60064, USA
| | - Walid M Awni
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Dept. R4PK, Bldg. AP31-3, 1 North Waukegan Road, North Chicago, IL, 60064, USA
| | - Sandeep Dutta
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Dept. R4PK, Bldg. AP31-3, 1 North Waukegan Road, North Chicago, IL, 60064, USA
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Abstract
Dasabuvir is a nonstructural (NS) 5B non-nucleoside inhibitor of the hepatitis C virus (HCV) used in combination with ombitasvir/paritaprevir/ritonavir for the treatment of chronic HCV infection. It is primarily metabolized by cytochrome P450 (CYP) 2C8, with a minor contribution from CYP3A. Biotransformation of dasabuvir forms the M1 metabolite, which retains antiviral activity. Dasabuvir exhibits linear pharmacokinetics with a terminal half-life of approximately 5-8 h, allowing for twice-daily dosing. The M1 metabolite of dasabuvir is the major metabolite in plasma and has a half-life similar to that of dasabuvir. Dasabuvir exposures in Asian subjects are comparable with Caucasian subjects. The pharmacokinetic characteristics of dasabuvir are similar between healthy subjects and HCV-infected patients, and are not appreciably altered by mild, moderate, or severe renal impairment or dialysis. Dasabuvir pharmacokinetic parameters were not significantly altered in subjects with mild or moderate hepatic impairment; however, exposures were significantly increased in subjects with severe hepatic impairment. Dasabuvir should be administered with food to maximize absorption. Coadministration of dasabuvir with a strong CYP2C8 inhibitor increased dasabuvir exposures by greater than tenfold, whereas coadministration with strong CYP3A inhibitors increased dasabuvir exposures by less than 50%. Furthermore, coadministration of dasabuvir with a CYP3A inducer decreased dasabuvir exposures by 55-70%. Coadministration of dasabuvir with strong CYP2C8 inhibitors or strong CYP3A/CYP2C8 inducers is contraindicated. Results from several drug interaction studies demonstrated that dasabuvir in combination with ombitasvir/paritaprevir/ritonavir can be coadministered with most comedications that are commonly prescribed in HCV-infected patients.
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Abstract
Ombitasvir is a potent, nonstructural protein 5A inhibitor of the hepatitis C virus (HCV) that is used in combination with other direct-acting antivirals for the treatment of chronic HCV infection. Ombitasvir is predominantly metabolized by amide hydrolysis followed by oxidative metabolism and is a substrate of P-glycoprotein. Ombitasvir displays linear pharmacokinetics with minimal accumulation and is eliminated via metabolism and biliary excretion. A negligible amount of unchanged drug is excreted in urine. Exposures are comparable across Chinese, Japanese, and non-Asian subjects. The pharmacokinetic characteristics of ombitasvir are similar in healthy subjects and HCV-infected patients, and are not appreciably altered by hepatic or renal impairment. Results from several drug interaction studies demonstrated that ombitasvir has a low potential for drug interactions.
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Affiliation(s)
- Prajakta S Badri
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Dept. R4PK, Bldg. AP31-3, 1 North Waukegan Road, North Chicago, IL, 60064, USA
| | - Diana L Shuster
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Dept. R4PK, Bldg. AP31-3, 1 North Waukegan Road, North Chicago, IL, 60064, USA
| | - Sandeep Dutta
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Dept. R4PK, Bldg. AP31-3, 1 North Waukegan Road, North Chicago, IL, 60064, USA
| | - Rajeev M Menon
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Dept. R4PK, Bldg. AP31-3, 1 North Waukegan Road, North Chicago, IL, 60064, USA.
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9
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Muñoz-Gómez R, Rincón D, Ahumada A, Hernández E, Devesa MJ, Izquierdo S, Ortiz M, Hernández-Albujar A, Fernández-Rodríguez C, Calvo M, González R, Lozano M, Castellano G, Fernández-Vázquez I. Therapy with ombitasvir/paritaprevir/ritonavir plus dasabuvir is effective and safe for the treatment of genotypes 1 and 4 hepatitis C virus (HCV) infection in patients with severe renal impairment: A multicentre experience. J Viral Hepat 2017; 24:464-471. [PMID: 27976490 DOI: 10.1111/jvh.12664] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2016] [Accepted: 11/28/2016] [Indexed: 12/16/2022]
Abstract
Limited data are available on direct-acting antivirals for treating hepatitis C virus (HCV) infection in patients with severe renal impairment. The aim of this study was to evaluate the effectiveness and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) ± dasabuvir (DSV) ± ribavirin (RBV) in patients with stage 4 or 5 chronic kidney disease (CKD) and HCV genotype 1 or 4 infection in real clinical practice, and to investigate pharmacological interactions. This retrospective study included patients treated with OBV/PTV/r+DSV±RBV or OBV/PTV/r+RBV with CKD stage 4 (eGFR: 15-29 mL/min/1.73m2 ) or 5 (eGFR<15 mL/min/1.73m2 or requiring dialysis) and HCV infection by genotypes 1 and 4 between April 2015 and October 2015 in nine Spanish centres. Sustained virological response at 12 weeks (SVR12) was assessed, and clinical and laboratory data, fibrosis stage, adverse events and pharmacological interactions were reported. Forty-six patients were included: 10 (21.7%) had CKD stage 4 and 36 (78.2%) CKD stage 5. Seventeen (36.9%) had cirrhosis. SVR12 rate in the intention-to-treat population was 95.7%. Twenty-one (45.6%) received RBV, which was discontinued in two (9.5%) patients. Anaemia (haemoglobin <10 g/dl) occurred in 12 patients (57.1%) with RBV vs 10 (40.0%) without RBV (P=.246). Renal function remained stable during antiviral therapy. Nine patients (19.5%) experienced serious adverse events unrelated to antiviral therapy. Concomitant medication was discontinued or modified in 41.3% of patients. In conclusion, the effectiveness of OBV/PTV/r±DSV±RBV in patients with CKD 4-5 was similar to that observed in those with normal renal function and was not associated with severe adverse events.
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Affiliation(s)
- R Muñoz-Gómez
- Department of Gastroenterology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - D Rincón
- Unit of Hepatology, Hospital Universitario Gregorio Marañón, CIBERehd , Madrid, Spain
| | - A Ahumada
- Unit of Hepatology, Hospital Universitario Gregorio Marañón, CIBERehd , Madrid, Spain
| | - E Hernández
- Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - M J Devesa
- Department of Gastroenterology, Hospital Universitario Clínico San Carlos, Madrid, Spain
| | - S Izquierdo
- Department of Gastroenterology, Hospital Universitario Clínico San Carlos, Madrid, Spain
| | - M Ortiz
- Department of Gastroenterology, Hospital Universitario Infanta Cristina, Madrid, Spain
| | - A Hernández-Albujar
- Department of Gastroenterology, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain
| | - C Fernández-Rodríguez
- Department of Gastroenterology, Hospital Universitario Fundación Alcorcón, Madrid, Spain
| | - M Calvo
- Department of Gastroenterology, Complejo Asistencial de Segovia, Segovia, Spain
| | - R González
- Department of Gastroenterology, Hospital Universitario del Sureste, Madrid, Spain
| | - M Lozano
- Department of Gastroenterology, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - G Castellano
- Department of Gastroenterology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - I Fernández-Vázquez
- Department of Gastroenterology, Hospital Universitario 12 de Octubre, Madrid, Spain
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Sato K, Hosonuma K, Yamazaki Y, Kobayashi T, Takakusagi S, Horiguchi N, Kakizaki S, Kusano M, Ohnishi H, Okamoto H, Yamada M. Combination Therapy with Ombitasvir/Paritaprevir/Ritonavir for Dialysis Patients Infected with Hepatitis C Virus: A Prospective Multi-Institutional Study. TOHOKU J EXP MED 2017; 241:45-53. [PMID: 28090038 DOI: 10.1620/tjem.241.45] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Hepatitis C virus (HCV) infection is common in dialysis patients worldwide and nosocomial HCV spread within dialysis facilities continues to develop. Combination therapy with daclatasvir and asunaprevir (DCV/ASV) that has proven efficacy for dialysis patients infected with genotype 1b HCV (HCV/1b) has several concerns in Japan. The recently available combination therapy with ombitasvir, paritaprevir, and ritonavir (OBV/PTV/r) is not contraindicated in patients with chronic renal failure and has more safety profile and shorter treatment period than that with DCV/ASV. We evaluated the effects of combination therapy with OBV/PTV/r in four dialysis patients infected with HCV/1b, who were eligible for our study. On-treatment assessments included standard laboratory testing, serum HCV RNA and symptom-directed physical examinations. Three patients had a sustained virological response at 12 weeks after treatment, but one remaining patient had viral breakthrough. Notably, the patient with viral breakthrough had been coinfected with HCV/1b and HCV/2b; namely, HCV/2b with resistance-associated variations was not eradicated by the combination therapy. Among the three patients responsive to the combination therapy, one patient complained of appetite loss and itching, while in another patient the therapy was discontinued due to itching, exacerbation of wamble, and a falling tendency probably due to interaction with valsartan. These AEs were ameliorated or disappeared after the completion of the therapy. The significance of our study is persuasive virological evaluation associated to the combination therapy and reasonable interpretation of AEs. In conclusion, combination therapy with OBV/PTV/r may have promise as an efficacious therapy, but caution regarding AEs should be practiced.
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Affiliation(s)
- Ken Sato
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine
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Mücke MM, Mücke VT, Lange CM, Zeuzem S. Special populations: treating hepatitis C in patients with decompensated cirrhosis and/or advanced renal impairment. Liver Int 2017; 37 Suppl 1:19-25. [PMID: 28052635 DOI: 10.1111/liv.13279] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Accepted: 10/14/2016] [Indexed: 12/21/2022]
Abstract
Direct-acting antivirals have revolutionized the treatment of hepatitis C. Sustained virological response rates of at least 95% have become common in the general population. However, along with the ageing of the HCV population, physicians face a growing group of HCV-infected patients with advanced liver and/or renal impairment. The safety and efficacy of treatment remains a clinical challenge in these patients. This review focuses on the current state of knowledge and treatment regimens in patients with decompensated cirrhosis and severe renal impairment. It shows that distinct interferon-free treatments can achieve favourable sustained virological response rates in these difficult-to-treat patients. Moreover, pitfalls and special considerations as well as new emerging challenges in an era of interferon-free regimens will be presented in this article.
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Affiliation(s)
- Marcus M Mücke
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt a.M., Germany
| | - Victoria T Mücke
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt a.M., Germany
| | - Christian M Lange
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt a.M., Germany
| | - Stefan Zeuzem
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt a.M., Germany
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Carrier P, Essig M, Debette-Gratien M, Sautereau D, Rousseau A, Marquet P, Jacques J, Loustaud-Ratti V. Anti-hepatitis C virus drugs and kidney. World J Hepatol 2016; 8:1343-1353. [PMID: 27917261 PMCID: PMC5114471 DOI: 10.4254/wjh.v8.i32.1343] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2016] [Revised: 07/08/2016] [Accepted: 09/18/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) mainly targets the liver but can also induce extrahepatic manifestations. The kidney may be impacted via an immune mediated mechanism or a cytopathic effect. HCV patients are clearly at a greater risk of chronic kidney disease (CKD) than uninfected patients are, and the presence of CKD increases mortality. Interferon-based therapies and ribavirin are difficult to manage and are poorly effective in end-stage renal disease and hemodialysis. These patients should be given priority treatment with new direct anti-viral agents (DAAs) while avoiding peginterferon and ribavirin. The first results were convincing. To aid in the correct use of these drugs in patients with renal insufficiency, their pharmacokinetic properties and potential renal toxicity must be known. The renal toxicity of these new drugs was not a safety signal in clinical trials, and the drugs are generally efficient in these frail populations. These drugs are usually well tolerated, but recent cohort studies have demonstrated that these new regimens may be associated with renal side effects, especially when using sofosbuvir combinations. HCV, renal diseases and comorbidities are intimately linked. The close monitoring of renal function is required, particularly for at-risk patients (transplanted, HIV-coinfected, CKD, hypertensive or diabetic patients). New DAA regimens, which will soon be approved, will probably change the landscape.
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