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Dashjamts G, Ganzorig AE, Tsedendorj Y, Daramjav D, Khayankhyarvaa E, Ulziitsogt B, Nergui O, Dondov G, Badamjav T, Lonjid T, Huang CF, Liang PC, Batsaikhan B, Dai CY. Change in Estimated Glomerular Filtration Rate After Direct-Acting Antiviral Treatment in Chronic Hepatitis C Patients. Diseases 2025; 13:26. [PMID: 39997033 PMCID: PMC11854603 DOI: 10.3390/diseases13020026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 01/17/2025] [Accepted: 01/17/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) infection accelerates the progression of chronic kidney disease (CKD), increasing the risk of kidney failure and end-stage renal disease. Direct-acting antiviral (DAA) therapies for HCV infection inhibit viral replication by 95-97%, leading to a sustained virologic response. Our objective was to assess renal function in patients with chronic HCV infection in Taiwan after receiving DAA therapy. GOAL Our study included 4823 patients with HCV infection who were undergoing DAA therapy. Renal function was evaluated by calculating the glomerular filtration rate (eGFR). eGFR assessed at the initiation of the treatment, during treatment, and at 3 months, 6 months, 1 year, and 3 years after completion of treatment. The baseline demographic and laboratory parameters of the study participants were evaluated, and the results were analyzed using statistical methods. RESULTS The average age of the study participants was 61.35 ± 12.50 years, and 54.5% of were male. The mean of eGFR in baseline and after treatment showed a decrease. Liver fibrosis scores (FIB4, APRI, Fibroscan) and liver function tests were significantly improved after DAA treatment (p = 0.001). However, white blood count (5.41 ± 1.7 vs. 5.73 ± 1.9), platelet count (168.04 ± 74.0 vs. 182.11 ± 69.4), and creatinine levels (1.05 ± 1.3 vs. 1.12 ± 1.3) increased after treatment (p = 0.001). The number of patients with an eGFR of 60 mL/min/1.73 m2 decreased both during and after treatment (p < 0.001). Among patients with CKD, eGFR improved after DAA treatment (n = 690, 35.93 ± 19.7 vs. 38.71 ± 23.8; 95% CI -3.56-1.98; p = 0.001). Logistic regression analysis revealed that renal function improved in patients with CKD who had an eGFR of less than 60 mL/min/1.73 m2 before DAA treatment (OR 1.62, 95% CI 1.37-1.91, p = 0.001). CONCLUSIONS In individuals with CKD and a baseline eGFR < 60 mL/min per 1.73 m2, eGFR level was increased during DAA treatment. This suggests that initiating DAA therapy in HCV-infected patients, even those without clinical manifestations, could be a crucial strategy to prevent further decline in renal function.
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Affiliation(s)
- Gantogtokh Dashjamts
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
| | - Amin-Erdene Ganzorig
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
| | - Yumchinsuren Tsedendorj
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
| | - Dolgion Daramjav
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
| | - Enkhmend Khayankhyarvaa
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
| | - Bolor Ulziitsogt
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
| | - Otgongerel Nergui
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
| | - Ganchimeg Dondov
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
| | - Tegshjargal Badamjav
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
- Department of Biological Sciences, School of Life Sciences, Inner Mongolia University, Hohhot 010031, China
| | - Tulgaa Lonjid
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
| | - Chung-Feng Huang
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; (C.-F.H.); (P.-C.L.)
- Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
| | - Po-Cheng Liang
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; (C.-F.H.); (P.-C.L.)
- Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
| | - Batbold Batsaikhan
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
- Department of Health Research, Graduate School, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia
| | - Chia-Yen Dai
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; (C.-F.H.); (P.-C.L.)
- Ph.D. Program in Environmental and Occupational Medicine, Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
- College of Professional Studies, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan
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Ratiu IA, Mihaescu A, Olariu N, Ratiu CA, Cristian BG, Ratiu A, Indries M, Fratila S, Dejeu D, Teusdea A, Ganea M, Moisa C, Marc L. Hepatitis C Virus Infection in Hemodialysis Patients in the Era of Direct-Acting Antiviral Treatment: Observational Study and Narrative Review. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:2093. [PMID: 39768975 PMCID: PMC11678887 DOI: 10.3390/medicina60122093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 12/16/2024] [Accepted: 12/18/2024] [Indexed: 01/05/2025]
Abstract
Background and Objectives: Hepatitis C virus (HCV) infection is a major global public health concern, particularly in hemodialysis (HD) patients. This study aims to evaluate the demographic, clinical, and laboratory characteristics of HCV-positive patients undergoing HD and assess the long-term impact of direct-acting antivirals (DAAs) on patient outcomes. Moreover, a narrative review aims to summarize the current knowledge regarding HCV treatment in HD patients. The search in the PubMed, Google Scholar, and Scopus databases identified 48 studies relevant to our topic, 18 regarding clinical history and 29 related to HCV treatment. Methods: A retrospective analysis was performed on 165 HD patients from Bihor County HD centers, Romania, between 2014 and 2024. The cohort was divided into two groups: 54 patients who tested positive for HCV and 111 controls who were HCV-negative. Data collected from GPs included demographic information, comorbidities, laboratory parameters, and psychological assessments. Outcomes were evaluated at over 5 years after DAA treatment. A literature review was conducted using PubMed and Google Scholar to identify relevant studies on HCV in HD patients from 1989 to 2024. Results: Laboratory results showed similar parameters across groups, except for lower serum cholesterol levels in the HCV-positive DAA-treated group vs. HCV-positive non-treated ones (155.607 mg% vs. 170.174 mg%, p = 0.040) and increased ALT levels when comparing the same groups (29.107 vs. 22.261, p = 0.027), whereas comorbidities did not differ significantly. The incidence of malignancies was significantly higher among HCV-positive compared to HCV-negative patients (20.3% vs. 8.1%, p = 0.023), mainly among those treated with DAAs, highlighted by the multivariate analysis. Cardiovascular disease remains the leading cause of mortality regardless of HCV status or the use of antiviral therapy. Psychological assessments revealed more severe depression in HCV-positive patients compared to their HCV-negative counterparts. Conclusions: HCV infection in the hemodialysis population typically follows a subclinical course. At over five years after DAA therapy, the results indicate a stabilization of the liver function and the absence of major complications. However, the incidence of malignancies remains high in HCV-positive patients.
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Affiliation(s)
- Ioana Adela Ratiu
- Faculty of Medicine and Pharmacy, University of Oradea, 1st December Square 10, 410073 Oradea, Romania; (I.A.R.); (B.G.C.); (M.I.); (S.F.); (D.D.); (M.G.)
- Nephrology Department, Emergency Clinical Hospital Bihor County, 12 Corneliu Coposu Street, 410469 Oradea, Romania
| | - Adelina Mihaescu
- Department of Internal Medicine II—Division of Nephrology, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (A.M.); (N.O.); (L.M.)
- Center for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania
| | - Nicu Olariu
- Department of Internal Medicine II—Division of Nephrology, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (A.M.); (N.O.); (L.M.)
- Center for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania
| | - Cristian Adrian Ratiu
- Dentistry Department, Faculty of Medicine and Pharmacy, University of Oradea, 1st December Square 10, 410073 Oradea, Romania;
| | - Bako Gabriel Cristian
- Faculty of Medicine and Pharmacy, University of Oradea, 1st December Square 10, 410073 Oradea, Romania; (I.A.R.); (B.G.C.); (M.I.); (S.F.); (D.D.); (M.G.)
- Nephrology Department, Emergency Clinical Hospital Bihor County, 12 Corneliu Coposu Street, 410469 Oradea, Romania
| | - Anamaria Ratiu
- Faculty of Dentistry, University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj-Napoca, Victor Babeș 8, 400347 Cluj-Napoca, Romania;
| | - Mirela Indries
- Faculty of Medicine and Pharmacy, University of Oradea, 1st December Square 10, 410073 Oradea, Romania; (I.A.R.); (B.G.C.); (M.I.); (S.F.); (D.D.); (M.G.)
- Infectious Diseases Department, Emergency Clinical Hospital, 410167 Bihor County, Romania
| | - Simona Fratila
- Faculty of Medicine and Pharmacy, University of Oradea, 1st December Square 10, 410073 Oradea, Romania; (I.A.R.); (B.G.C.); (M.I.); (S.F.); (D.D.); (M.G.)
| | - Danut Dejeu
- Faculty of Medicine and Pharmacy, University of Oradea, 1st December Square 10, 410073 Oradea, Romania; (I.A.R.); (B.G.C.); (M.I.); (S.F.); (D.D.); (M.G.)
| | - Alin Teusdea
- Faculty of Environmental Protection, University of Oradea, G-ral Magheru 27, 410087 Oradea, Romania;
| | - Mariana Ganea
- Faculty of Medicine and Pharmacy, University of Oradea, 1st December Square 10, 410073 Oradea, Romania; (I.A.R.); (B.G.C.); (M.I.); (S.F.); (D.D.); (M.G.)
| | - Corina Moisa
- Faculty of Medicine and Pharmacy, University of Oradea, 1st December Square 10, 410073 Oradea, Romania; (I.A.R.); (B.G.C.); (M.I.); (S.F.); (D.D.); (M.G.)
| | - Luciana Marc
- Department of Internal Medicine II—Division of Nephrology, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (A.M.); (N.O.); (L.M.)
- Center for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania
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Nawaz R, Ahmad M, Raza MS, Rashad M, Nawaz A, Tabassum K, Hassan JU, Ahad A, Idrees M. Coincidence of HCV and chronic kidney disease-a systematic review and meta-analysis. BMC Public Health 2024; 24:2842. [PMID: 39415151 PMCID: PMC11481586 DOI: 10.1186/s12889-024-20331-0] [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: 01/07/2024] [Accepted: 10/08/2024] [Indexed: 10/18/2024] Open
Abstract
BACKGROUND There are reported studies of Hepatitis C and chronic kidney disease association. However, how this liver virus infection affects the general population's susceptibility to the onset of the kidney disease is still unknown. METHODS To determine if a positive anti-HCV serologic status is linked to a greater incidence of chronic kidney disease in the general adult population, a systematic evaluation of the published medical literature since 2015 was conducted. A summary estimate of the relative risk of chronic kidney disease with HCV was produced using a random-effects model. Moreover, stratified analysis and meta-regression were performed. RESULTS Twelve studies (n = 605858 patients) were filtered and included. Meta-analyses were conducted according to the outcome. Pooling results of longitudinal studies (n = 06 studies, n = 347120 unique patients) demonstrated an association between positive anti-HCV serologic status and increased incidence of CKD. The summary estimate for adjusted hazard ratio was 1.21 with (95% confidence interval 1.13; 1.29, P = 0.001), and between studies heterogeneity was noted (P value by Q test < 0.001). In the subset of Asian surveys, the risk of the occurrence of chronic kidney disease linked to HCV was 1.70 (95% confidence interval 1.40; 2.00) without heterogeneity (P value by Q test = 0.6). CONCLUSIONS We found a strong correlation between HCV infection and a higher risk of chronic renal disease in general global population.
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Affiliation(s)
- Rabia Nawaz
- Department of Biological Sciences, Superior University, Lahore, 53700, Pakistan.
- Division of Molecular Virology, Center of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
| | - Muhammad Ahmad
- Department of Biological Sciences, Superior University, Lahore, 53700, Pakistan
| | - Muhammad Saad Raza
- Department of Biological Sciences, Superior University, Lahore, 53700, Pakistan
| | - Muhammad Rashad
- Department of Biological Sciences, Superior University, Lahore, 53700, Pakistan
| | - Ayesha Nawaz
- Department of Biological Sciences, Superior University, Lahore, 53700, Pakistan
| | - Khadija Tabassum
- Department of Biological Sciences, Superior University, Lahore, 53700, Pakistan
| | | | - Ammara Ahad
- Department of Biological Sciences, Superior University, Lahore, 53700, Pakistan
| | - Muhammad Idrees
- Division of Molecular Virology, Center of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan
- Vice chancellor, University of Peshawar, Peshawar, Pakistan
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Aljarallah BM. Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir in Treating HCV Genotypes 1 and 4 in Patients with Advanced Chronic Kidney Disease. JOURNAL OF PHARMACY AND BIOALLIED SCIENCES 2024; 16:S2224-S2227. [PMID: 39346174 PMCID: PMC11426834 DOI: 10.4103/jpbs.jpbs_143_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Revised: 03/03/2024] [Accepted: 03/12/2024] [Indexed: 10/01/2024] Open
Abstract
This study assessed the efficacy and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) combined with dasabuvir (DSV) for treating hepatitis C genotype 4 (GT4) and genotype 1 (GT1) in patients with stage 4 or 5 chronic kidney disease (CKD). Among 88 patients, including treatment-naïve and Peginterferon/Ribavirin (RBV)-experienced, treated with OBV/PTV/r±RBV (dosed between 200 mg per week to daily) and additional DSV for GT1, 94.3% achieved sustained virologic response at 12 weeks (SVR12), demonstrating high efficacy. RBV was used at the discretion of the treating physician. The treatment was well-tolerated, with two non-treatment-related deaths reported. The findings suggest that a 12-week regimen of OBV/PTV/r±DSV is highly effective and safe for GT1 and GT4 patients with advanced CKD, regardless of baseline characteristics.
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Affiliation(s)
- Badr M. Aljarallah
- Department of Medicine, Division of Gastroenterology and Hepatology, College of Medicine, Qassim University, Buraydah, Saudi Arabia
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Kamal S, Shahzad A, Rehman K, Tariq K, Akash MSH, Imran M, Assiri MA. Therapeutic Intervention of Serine Protease Inhibitors against Hepatitis C Virus. Curr Med Chem 2024; 31:2052-2072. [PMID: 37855348 DOI: 10.2174/0109298673234823230921090431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 05/12/2023] [Accepted: 05/23/2023] [Indexed: 10/20/2023]
Abstract
Hepatitis C virus (HCV) is a globally prevalent and hazardous disorder that is responsible for inducing several persistent and potentially fatal liver diseases. Current treatment strategies offer limited efficacy, often accompanied by severe and debilitating adverse effects. Consequently, there is an urgent and compelling need to develop novel therapeutic interventions that can provide maximum efficacy in combating HCV while minimizing the burden of adverse effects on patients. One promising target against HCV is the NS3-4A serine protease, a complex composed of two HCV-encoded proteins. This non-covalent heterodimer is crucial in the viral life cycle and has become a primary focus for therapeutic interventions. Although peginterferon, combined with ribavirin, is commonly employed for HCV treatment, its efficacy is hampered by significant adverse effects that can profoundly impact patients' quality of life. In recent years, the development of direct-acting antiviral agents (DAAs) has emerged as a breakthrough in HCV therapy. These agents exhibit remarkable potency against the virus and have demonstrated fewer adverse effects when combined with other DAAs. However, it is important to note that there is a potential for developing resistance to DAAs due to alterations in the amino acid position of the NS3-4A protease. This emphasizes the need for ongoing research to identify strategies that can minimize the emergence of resistance and ensure long-term effectiveness. While the combination of DAAs holds promise for HCV treatment, it is crucial to consider the possibility of drug-drug interactions. These interactions may occur when different DAAs are used concurrently, potentially compromising their therapeutic efficacy. Therefore, carefully evaluating and monitoring potential drug interactions are vital to optimize treatment outcomes. In the pursuit of novel therapeutic interventions for HCV, the field of computational biology and bioinformatics has emerged as a valuable tool. These advanced technologies and methodologies enable the development and design of new drugs and therapeutic agents that exhibit maximum efficacy, reduced risk of resistance, and minimal adverse effects. By leveraging computational approaches, researchers can efficiently screen and optimize potential candidates, accelerating the discovery and development of highly effective treatments for HCV, treatments.
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Affiliation(s)
- Shagufta Kamal
- Department of Biochemistry, Government College University, Faisalabad, Pakistan
| | - Asif Shahzad
- Department of Biochemistry, Government College University, Faisalabad, Pakistan
| | - Kanwal Rehman
- Department of Pharmacy, The Women University, Multan, Pakistan
| | - Komal Tariq
- Department of Biochemistry, Government College University, Faisalabad, Pakistan
| | | | - Muhammad Imran
- Research center for Advanced Materials Science (RCAMS), King Khalid University, Abha, Saudi Arabia
- Department of Chemistry, Faculty of Science, King Khalid University, Abha, Saudi Arabia
| | - Mohammed Ali Assiri
- Research center for Advanced Materials Science (RCAMS), King Khalid University, Abha, Saudi Arabia
- Department of Chemistry, Faculty of Science, King Khalid University, Abha, Saudi Arabia
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Toyoda H, Kikuchi K. Management of dialysis patients with hepatitis C virus in the era of direct-acting antiviral therapy. Ther Apher Dial 2023; 27:831-838. [PMID: 37217295 DOI: 10.1111/1744-9987.14003] [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: 03/03/2023] [Revised: 04/24/2023] [Accepted: 05/06/2023] [Indexed: 05/24/2023]
Abstract
The clinical use of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection has dramatically changed management of patients with HCV liver disease since 2014; this is also true for patients undergoing dialysis. Due to the high tolerability and antiviral efficacy of anti-HCV therapy, most dialysis patients with HCV infection should currently be candidates for this treatment. Many patients with HCV antibodies no longer have HCV infection, and it is difficult to identify patients with actual HCV infection based only on HCV antibody assays. Despite the high rate of successful HCV eradication, the risk of liver-related events such as hepatocellular carcinoma (HCC), the major complication of HCV infection, persists even after HCV cure, and patients at risk of HCC should undergo continuous HCC surveillance. Finally, the rarity of HCV reinfection and the survival benefit of HCV eradication in dialysis patients should be explored in further studies.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Kan Kikuchi
- Division of Nephrology, Shimoochiai Clinic, Tokyo, Japan
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Chen R, Xiong Y, Zeng Y, Wang X, Xiao Y, Zheng Y. The efficacy and safety of direct-acting antiviral regimens for end-stage renal disease patients with HCV infection: a systematic review and network meta-analysis. Front Public Health 2023; 11:1179531. [PMID: 37841743 PMCID: PMC10570741 DOI: 10.3389/fpubh.2023.1179531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Accepted: 08/31/2023] [Indexed: 10/17/2023] Open
Abstract
Background Hepatitis C virus (HCV) infection is an independent risk factor associated with adverse outcomes in patients with end-stage renal disease (ESRD). Due to the wide variety of direct-acting antiviral regimens (DAAs) and the factor of renal insufficiency, careless selection of anti-hepatitis C treatment can lead to treatment failure and safety problems. The integrated evidence for optimized therapies for these patients is lacking. This study would conduct comparisons of different DAAs and facilitate clinical decision-making. Methods We conducted a systematic literature search in multiple databases (PubMed, Ovid, Embase, Cochrane Library, and Web of Science) up to 7 August 2023. Study data that contained patient characteristics, study design, treatment regimens, intention-to-treat sustained virologic response (SVR), and adverse event (AE) data per regimen were extracted into a structured electronic database and analyzed. The network meta-analysis of the estimation was performed by the Bayesian Markov Chain Monte Carlo methods. Results Our search identified 5,278 articles; removing the studies with duplicates and ineligible criteria, a total of 62 studies (comprising 4,554 patients) were included. Overall, the analyses contained more than 2,489 male individuals, at least 202 patients with cirrhosis, and no less than 2,377 patients under hemodialysis. Network meta-analyses of the DAAs found that receiving ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (R) plus dasabuvir (DSV), glecaprevir (G)/pibrentasvir (P), and sofosbuvir (SOF)/ledipasvir (LDV) ranked as the top three efficacy factors for the HCV-infected ESRD patients. Stratified by genotype, the G/P would prioritize genotype 1 and 2 patients with 98.9%-100% SVR, the SOF/DCV regimen had the greatest SVR rates (98.7%; 95% CI, 93.0%-100.0%) in genotype 3, and the OBV/PTV/R regimen was the best choice for genotype 4, with the highest SVR of 98.1% (95% CI, 94.4%-99.9%). In the pan-genotypic DAAs comparison, the G/P regimen showed the best pooled SVR of 99.4% (95% CI, 98.6%-100%). DAA regimens without Ribavirin or SOF showed the lowest rates of AEs (49.9%; 95% CI, 38.4%-61.5%) in HCV-infected ESRD patients. Conclusion The G/P could be recommended as the best option for the treatment of pan-genotypic HCV-infected ESRD patients. The OBV/PTV/R plus DSV, SOF/Velpatasvir (VEL), SOF/Ledipasvir (LDV), and SOF/DCV would be reliable alternatives for HCV treatment with comparable efficacy and safety profiles. Systematic review registration https://www.crd.york.ac.uk/prospero/#searchadvanced, PROSPERO: CRD42021242359.
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Affiliation(s)
- Ruochan Chen
- Key Laboratory of Viral Hepatitis of Hunan, Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Yinghui Xiong
- Department of Respiration, Hunan Children's Hospital, Changsha, China
| | - Yanyang Zeng
- Key Laboratory of Viral Hepatitis of Hunan, Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Xiaolei Wang
- Hunan Provincial Center for Disease Control and Prevention, Hunan Workstation for Emerging Infectious Disease Control and Prevention, Chinese Academy of Medical Sciences, Changsha, China
| | - Yinzong Xiao
- Burnet Institute, St Vincent's Hospital, University of Melbourne, Melbourne, VIC, Australia
| | - Yixiang Zheng
- Key Laboratory of Viral Hepatitis of Hunan, Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
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Ivashkin VT, Chulanov VP, Mamonova NA, Maevskaya MV, Zharkova MS, Tikhonov IN, Bogomolov PO, Volchkova EV, Dmitriev AS, Znojko OO, Klimova EA, Kozlov KV, Kravchenko IE, Malinnikova EY, Maslennikov RV, Mikhailov MI, Novak KE, Nikitin IG, Syutkin VE, Esaulenko EV, Sheptulin AA, Shirokova EN, Yushchuk ND. Clinical Practice Guidelines of the Russian Society for the Study of the Liver, the Russian Gastroenterological Association, the National Scientific Society of Infectious Disease Specialists for the Diagnosis and Treatment of Chronic Hepatitis C. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2023; 33:84-124. [DOI: 10.22416/1382-4376-2023-33-1-84-124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/26/2024]
Abstract
Аim:diagnosis and treatment algorithms in the clinical recommendations intended for general practitioners, gastroenterologists, infectious disease specialists, hepatologists on the of chronic hepatitis C are presented.Summary.Chronic viral hepatitis C is a socially significant infection, the incidence of which in the Russian Federation remains significantly high. Over the past 10 years, great progress has been made in the treatment of hepatitis C — direct acting antiviral drugs have appeared. The spectrum of their effectiveness allows to achieve a sustained virological response in more than 90 % of cases, even in groups that were not previously considered even as candidates for therapy or were difficult to treat — patients receiving renal replacement therapy, after liver transplantation (or other organs), at the stage of decompensated liver cirrhosis, HIV co-infected, etc. Interferons are excluded from the recommendations due to their low effectiveness and a wide range of adverse events. The indications for the treatment have been expanded, namely, the fact of confirmation of viral replication. The terms of dispensary observation of patients without cirrhosis of the liver have been reduced (up to 12 weeks after the end of therapy). Also, these recommendations present approaches to active screening of hepatitis in risk groups, preventive and rehabilitation measures after the end of treatment.Conclusion.Great success has been achieved in the treatment of chronic hepatitis C. In most cases, eradication of viral HCV infection is a real task even in patients at the stage of cirrhosis of the liver, with impaired renal function, HIV co-infection, after solid organs transplantation.
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Affiliation(s)
- V. T. Ivashkin
- Sechenov First Moscow State Medical University (Sechenov University)
| | - V. P. Chulanov
- Center for Epidemiologically Significant Infectious Diseases, National Medical Research Center for Phthisiopulmonology and Infectious Diseases
| | - N. A. Mamonova
- Center for Epidemiologically Significant Infectious Diseases, National Medical Research Center for Phthisiopulmonology and Infectious Diseases
| | - M. V. Maevskaya
- Sechenov First Moscow State Medical University (Sechenov University)
| | - M. S. Zharkova
- Sechenov First Moscow State Medical University (Sechenov University)
| | - I. N. Tikhonov
- Sechenov First Moscow State Medical University (Sechenov University)
| | - P. O. Bogomolov
- M.F. Vladimirsky Moscow Regional Research Clinical Institute
| | - E. V. Volchkova
- Sechenov First Moscow State Medical University (Sechenov University)
| | - A. S. Dmitriev
- Sechenov First Moscow State Medical University (Sechenov University)
| | - O. O. Znojko
- Moscow State University of Medicine and Dentistry
| | | | | | | | - E. Yu. Malinnikova
- Department of Virology, Russian Medical Academy of Continuing Professional Education
| | - R. V. Maslennikov
- Sechenov First Moscow State Medical University (Sechenov University)
| | - M. I. Mikhailov
- North-Western State Medical University named after I.I. Mechnikov
| | | | | | - V. E. Syutkin
- Sklifosovsky Clinical and Research Institute for Emergency Medicine; Russian State Research Center — Burnazyan Federal Medical Biophysical Center
| | | | - A. A. Sheptulin
- Sechenov First Moscow State Medical University (Sechenov University)
| | - E. N. Shirokova
- Sechenov First Moscow State Medical University (Sechenov University)
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Kovács ZM, Óvári J, Dienes C, Magyar J, Bányász T, Nánási PP, Horváth B, Feher A, Varga Z, Szentandrássy N. ABT-333 (Dasabuvir) Increases Action Potential Duration and Provokes Early Afterdepolarizations in Canine Left Ventricular Cells via Inhibition of I Kr. Pharmaceuticals (Basel) 2023; 16:488. [PMID: 37111245 PMCID: PMC10143825 DOI: 10.3390/ph16040488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Revised: 03/17/2023] [Accepted: 03/22/2023] [Indexed: 03/29/2023] Open
Abstract
ABT-333 (dasabuvir) is an antiviral agent used in hepatitis C treatment. The molecule, similarly to some inhibitors of hERG channels, responsible for the delayed rectifier potassium current (IKr), contains the methanesulfonamide group. Reduced IKr current leads to long QT syndrome and early afterdepolarizations (EADs), therefore potentially causing life-threatening arrhythmias and sudden cardiac death. Our goal was to investigate the acute effects of ABT-333 in enzymatically isolated canine left ventricular myocardial cells. Action potentials (APs) and ion currents were recorded with a sharp microelectrode technique and whole-cell patch clamp, respectively. Application of 1 μM ABT-333 prolonged the AP in a reversible manner. The maximal rates of phases 0 and 1 were irreversibly decreased. Higher ABT-333 concentrations caused larger AP prolongation, elevation of the early plateau potential, and reduction of maximal rates of phases 0, 1, and 3. EADs occurred in some cells in 3-30 μM ABT-333 concentrations. The 10 μM ABT-333-sensitive current, recorded with AP voltage clamp, contained a late outward component corresponding to IKr and an early outward one corresponding to transient outward potassium current (Ito). ABT-333 reduced hERG-channel-mediated ion current in a concentration-dependent, partially reversible manner with a half-inhibitory concentration of 3.2 μM. As the therapeutic plasma concentration of ABT-333 can reach the low μM range, ABT-333 application carries a risk of cardiac side effects especially in case of coadministration with strong inhibitors of CYP2C8.
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Affiliation(s)
- Zsigmond Máté Kovács
- Department of Physiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
- Doctoral School of Molecular Medicine, University of Debrecen, H-4032 Debrecen, Hungary
| | - József Óvári
- Department of Physiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
- Doctoral School of Dental Sciences, University of Debrecen, H-4032 Debrecen, Hungary
| | - Csaba Dienes
- Department of Physiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
- Doctoral School of Molecular Medicine, University of Debrecen, H-4032 Debrecen, Hungary
| | - János Magyar
- Department of Physiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
- Division of Sport Physiology, Department of Physiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
| | - Tamás Bányász
- Department of Physiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
| | - Péter P. Nánási
- Department of Physiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
- Department of Dental Physiology and Pharmacology, Faculty of Dentistry, University of Debrecen, H-4032 Debrecen, Hungary
| | - Balázs Horváth
- Department of Physiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
| | - Adam Feher
- Doctoral School of Molecular Medicine, University of Debrecen, H-4032 Debrecen, Hungary
- Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
| | - Zoltan Varga
- Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
| | - Norbert Szentandrássy
- Department of Physiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
- Department of Basic Medical Sciences, Faculty of Dentistry, University of Debrecen, H-4032 Debrecen, Hungary
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Liu CH, Fang YJ, Liu CJ, Su TH, Huang SC, Tseng TC, Wu JH, Chen PJ, Kao JH. Splenic Arterial Pulsatility Index to Predict Hepatic Fibrosis in Hemodialysis Patients with Chronic Hepatitis C Virus Infection. J Clin Med 2023; 12:jcm12052020. [PMID: 36902807 PMCID: PMC10004191 DOI: 10.3390/jcm12052020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 02/27/2023] [Accepted: 03/02/2023] [Indexed: 03/08/2023] Open
Abstract
The clinical utility of the splenic arterial pulsatility index (SAPI), a duplex Doppler ultrasonographic index, to predict the stage of hepatic fibrosis in hemodialysis patients with chronic hepatitis C virus (HCV) infection remains elusive. We conducted a retrospective, cross-sectional study to include 296 hemodialysis patients with HCV who underwent SAPI assessment and liver stiffness measurements (LSMs). The levels of SAPI were significantly associated with LSMs (Pearson correlation coefficient: 0.413, p < 0.001) and different stages of hepatic fibrosis as determined using LSMs (Spearman's rank correlation coefficient: 0.529, p < 0.001). The areas under receiver operating characteristics (AUROCs) of SAPI to predict the severity of hepatic fibrosis were 0.730 (95% CI: 0.671-0.789) for ≥F1, 0.782 (95% CI: 0.730-0.834) for ≥F2, 0.838 (95% CI: 0.781-0.894) for ≥F3, and 0.851 (95% CI: 0.771-0.931) for F4. Furthermore, the AUROCs of SAPI were comparable to those of the fibrosis index based on four parameters (FIB-4) and superior to those of the aspartate transaminase (AST)-to-platelet ratio index (APRI). The positive predictive value (PPV) for ≥F1 was 79.5% when the Youden index was set at 1.04, and the negative predictive values (NPVs) for ≥F2, ≥F3, and F4 were 79.8%, 92,6%, and 96.9%, respectively, when the maximal Youden indices were set at 1.06, 1.19, and 1.30. The diagnostic accuracies of SAPI with the maximal Youden index for a fibrosis stage of ≥F1, ≥F2, ≥F3, and F4 were 69.6%, 67.2%, 75.0%, and 85.1%, respectively. In conclusion, SAPI can serve as a good noninvasive index in predicting the severity of hepatic fibrosis in hemodialysis patients with chronic HCV infection.
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Affiliation(s)
- Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei 100225, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei 100225, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Douliou 640203, Taiwan
- Correspondence: (C.-H.L.); (J.-H.K.); Tel.: +886-2-23123456 (ext. 63572) (C.-H.L.); +886-2-23123456 (ext. 67307) (J.-H.K.)
| | - Yu-Jen Fang
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Douliou 640203, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei 100225, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei 100225, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 100233, Taiwan
| | - Tung-Hung Su
- Department of Internal Medicine, National Taiwan University Hospital, Taipei 100225, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei 100225, Taiwan
| | - Shang-Chin Huang
- Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei 108206, Taiwan
| | - Tai-Chung Tseng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei 100225, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei 100225, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei 100225, Taiwan
| | - Jo-Hsuan Wu
- Hamilton Glaucoma Center, Shiley Eye Institute and Viterbi Family Department of Ophthalmology, University of California, San Diego, CA 92039, USA
| | - Pei-Jer Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei 100225, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei 100225, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 100233, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei 100225, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei 100225, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 100233, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei 100225, Taiwan
- Correspondence: (C.-H.L.); (J.-H.K.); Tel.: +886-2-23123456 (ext. 63572) (C.-H.L.); +886-2-23123456 (ext. 67307) (J.-H.K.)
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El-Sayed M, Elserafy M, El Raziky M, Elakel W, Saad Y, Fayad T, Korany M, Mehrez M, Salama R, Mahrous M, Zaki A, Hassany M, Ammar I, Elsaeed K, Elshazly Y, Doss W. Efficacy and safety of ombitasvir/paritaprevir/ritonavir-based therapy in HCV patients with chronic kidney disease. Arab J Gastroenterol 2023; 24:29-33. [PMID: 36813580 DOI: 10.1016/j.ajg.2022.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 12/05/2021] [Accepted: 10/12/2022] [Indexed: 02/22/2023]
Abstract
BACKGROUND AND STUDY AIMS Hepatitis C virus (HCV) prevalence inchronic kidney disease (CKD) patients is significantly higher than in the general population. This study evaluated the efficacy and safety of combined ombitasvir/paritaprevir/ritonavir-based therapy in HCV patients with renal impairment. PATIENTS AND METHODS Our study included 829 patients with normal kidney functions (group 1) and 829 patients with CKD (group 2),which were subdivided into patients not requiring dialysis (group 2a) and those on hemodialysis (group2b). Patients received regimens of ombitasvir/paritaprevir/ritonavir with or without ribavirin or sofosbuvir/ombitasvir/paritaprevir/ritonavir with or without ribavirin for 12 weeks. Clinical and laboratory assessment was done before treatment, and patients were followed up for12 weeks after treatment. RESULTS The sustained virological response (SVR) at week 12 was significantly higher in group 1 than in the other three groups/subgroups, being 94.2% vs 90.2%, 90%, and 90.7%, respectively. The regimen with the highest SVR was ombitasvir/paritaprevir/ritonavir with ribavirin. The most common adverse event was anemia, which was more common in group 2. CONCLUSION Ombitasvir/paritaprevir/ritonavir-based therapy in chronic HCV patients with CKD is highly effective, with minimal side effects despite ribavirin-induced anemia.
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Affiliation(s)
- Mohammad El-Sayed
- Department of Endemic Medicine and Hepatogastroenterology, Cairo University, Cairo, Egypt
| | - Magdy Elserafy
- Department of Endemic Medicine and Hepatogastroenterology, Cairo University, Cairo, Egypt
| | - Maissa El Raziky
- Department of Endemic Medicine and Hepatogastroenterology, Cairo University, Cairo, Egypt
| | - Wafaa Elakel
- Department of Endemic Medicine and Hepatogastroenterology, Cairo University, Cairo, Egypt
| | - Yasmin Saad
- Department of Endemic Medicine and Hepatogastroenterology, Cairo University, Cairo, Egypt
| | - Tarek Fayad
- Department of Internal Medicine and Nephrology, Cairo University, Cairo, Egypt
| | | | - Mai Mehrez
- National Hepatology and Tropical Medicine Research Institute (NHTMRI), Cairo, Egypt
| | - Rabab Salama
- Department of Endemic Medicine and Hepatogastroenterology, Cairo University, Cairo, Egypt
| | | | - Ayman Zaki
- Gastroenterology and Hepatology Unit, Al-Ahrar Educational Hospital, Sharkia, Egypt
| | - Mohamed Hassany
- National Hepatology and Tropical Medicine Research Institute (NHTMRI), Cairo, Egypt
| | - Islam Ammar
- Department of Hepatology, Gastroenterology and Infectious Diseases, Al Azhar University, Cairo, Egypt.
| | - Kadry Elsaeed
- Department of Internal Medicine, Ain Shams University, Cairo, Egypt
| | - Yehia Elshazly
- Department of Internal Medicine, Ain Shams University, Cairo, Egypt
| | - Wahid Doss
- Department of Endemic Medicine and Hepatogastroenterology, Cairo University, Cairo, Egypt
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Balk EM, Adam GP, Jadoul M, Martin P, Gordon CE. A Systematic Review of Direct-Acting Antivirals for Hepatitis C in Advanced CKD. Kidney Int Rep 2023; 8:240-253. [PMID: 36815114 PMCID: PMC9939364 DOI: 10.1016/j.ekir.2022.11.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 11/11/2022] [Accepted: 11/15/2022] [Indexed: 12/03/2022] Open
Abstract
Introduction Direct-acting antivirals (DAAs) have improved treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD). To facilitate the 2022 update of the Kidney Disease: Improving Global Outcomes (KDIGO) guideline for CKD patients with HCV, we systematically reviewed DAA regimens in patients with CKD stages G4 and G5 nondialysis (G4-G5ND), CKD stage G5 on dialysis (G5D), and kidney transplant recipients (KTRs). Methods We conducted a systematic review by searching PubMed, Embase, Cochrane, CINAHL, and ClinicalTrials.gov through February 1, 2022, and conferences from 2019 to 2021. Studies of HCV-infected patients with CKD G4-G5ND, G5D, and KTRs treated with specified DAA regimens were included. Outcomes included death at 6 months or later, sustained virologic response at 12 weeks (SVR12), serious adverse events (SAEs) attributed to DAA, and treatment discontinuation because of adverse events. Maximum likelihood meta-analyses were determined; certainty of evidence was assessed per GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Results We identified 106 eligible studies (22 reported on CKD G4-G5ND, 69 on CKD G5D, and 29 on KTRs). In each population, the majority of DAA regimens achieved SVR12 ≥ 93%. We found generally low quality of evidence of low risk of SAEs (mostly 0%, up to 2.9%) and low risk of discontinuation because of adverse events (mostly 0%-5%). Across 3 unadjusted observational studies in KTRs, the risk of death after DAA treatment was substantially lower than without treatment (summary odds ratio, 0.16; 95% CI, 0.04-0.61). Conclusion Combination DAA regimens are safe and highly effective in patients with advanced CKD, on dialysis, and with kidney transplants.
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Affiliation(s)
- Ethan M. Balk
- Brown Center for Evidence Synthesis in Health, Brown School of Public Health, Brown University, Providence, Rhode Island, USA
| | - Gaelen P. Adam
- Brown Center for Evidence Synthesis in Health, Brown School of Public Health, Brown University, Providence, Rhode Island, USA
| | - Michel Jadoul
- Department of Nephrology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
| | - Paul Martin
- Division of Digestive Health and Liver Diseases, University of Miami School of Medicine, Miami, Florida, USA
| | - Craig E. Gordon
- Division of Nephrology, Department of Medicine, Tufts University School of Medicine, Boston, Massachussetts, USA
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Assessment of alteration in antiviral plasma concentration across dialysis days: computational and analytical study. Bioanalysis 2022; 14:1563-1581. [PMID: 36846891 DOI: 10.4155/bio-2022-0218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2023] Open
Abstract
Aim: Protein-bound uremic toxins (PBUTs) may displace drugs from the plasma proteins and render them more liable to clearance. This study aims to investigate the possible interplay between PBUTs and directly acting antivirals (DAAs). Methods: PBUT plasma protein binding was compared to those of paritaprevir (PRT), ombitasivir (OMB) and ritonavir (RTV) in silico to assess the possible competitive displacement. The three drugs were LC-MS/MS determined in seven patients across dialysis and non-dialysis days and results were compared. Results & conclusion: Results showed that the PBUT exhibited a lower binding than DAA reducing the liability of their competitive displacement. This was echoed by an unaltered plasma concentration across dialysis days. Results may indicate that PBUT accumulation may have limited effect on disposition of DAA.
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George Michael T, Anwar CA, Ahmed OA, Sarhan I, Elshazly Y, Shaker MK, Eltabbakh M, Hashem W, Tawfic SR, Kamel SY, Kandil DM, Naguib GG, Khedr A, Ghanem EA, Dabbous H, Doss W, El-Sayed MH. Micro-elimination of hepatitis C in patients with chronic kidney disease: an Egyptian single-center study. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2022. [DOI: 10.1186/s43162-022-00139-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background and aims
Micro-elimination of hepatitis C in renal patients is crucial. This study aims to assess the efficacy and safety of directly acting antivirals in chronic kidney disease patients and the effect of treatment on kidney functions.
Results
This prospective cohort study included 77 chronic HCV-infected patients with chronic kidney disease. Patients were consented and treated for 12 weeks with either sofosbuvir and daclatasvir ± ribavirin if glomerular filtration rate was > 30 mL/min per 1.73m2 or ritonavir-boosted paritaprevir-ombitasvir-ribavirin if it was < 30 mL/min per 1.73m2. Patients were divided into two categories (responders versus non-responders). Predictors of response to treatment were statistically analyzed through logistic regression analysis. Sixty-two patients received ritonavir-boosted paritaprevir-ombitasvir-ribavirin, 3 received sofosbuvir and daclatasvir, and 12 received sofosbuvir and daclatasvir plus ribavirin. Most patients were on hemodialysis (n = 36) while 31 were stage 3 kidney disease. All patients completed their treatment course; ribavirin doses were adjusted or stopped in patients who developed anemia (40%). Seventy-two patients (93.5%) achieved sustained virological response 12 weeks following end-of-treatment. Five patients (6.5%) were non-responders, 4 of whom were on hemodialysis (p = 0.179). All non-responders were on ritonavir-boosted paritaprevir-ombitasvir-ribavirin. The mean serum creatinine level at weeks 4 and 8 of treatment demonstrated significant improvement compared to pretreatment values (p < 0.001) in patients on conservative therapy.
Conclusion
Treatment of chronic kidney disease patients for chronic hepatitis C with directly acting antivirals is safe, efficacious with high response rates and likely to improve renal functions if started early in the course of kidney disease.
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Jadoul M, Awan A, Berenguer M, Bruchfeld A, Fabrizi F, Goldberg D, Jia J, Kamar N, Mohamed R, Pessôa M, Pol S, Sise M, Martin P. KDIGO 2022 Clinical Practice Guideline FOR the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int 2022; 102:S129-S205. [PMID: 36410841 DOI: 10.1016/j.kint.2022.07.013] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 07/27/2022] [Indexed: 11/19/2022]
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ERÜRKER ÖZTÜRK T, GÜREL S, ORUÇ A, ERSOY A. The efficacy of the direct-acting antiviral combination in hemodialysis patients with chronic hepatitis C virus Genotype 1 infection. TURKISH JOURNAL OF INTERNAL MEDICINE 2022. [DOI: 10.46310/tjim.994659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Background Interferon and ribavirin treatments previously used in treating chronic hepatitis C virus (HCV) infection cannot be used effectively in hemodialysis patients due to dose adjustment and drug-related side effects. Direct-acting antivirals (DAAs) therapies have been reported to be effective in hemodialysis patients. This study aimed to evaluate the effectiveness of DAAs in hemodialysis patients with chronic hepatitis C.
Material and Methods Twenty hemodialysis patients with chronic hepatitis C followed in the gastroenterology outpatient clinic between 2016 and 2018 were evaluated retrospectively.
Results Twelve of the 20 patients were male, and eight were female. The mean age of the patients was 50.7±8.6 years. Six patients had no treatment experience. Fourteen patients had been previously treated with interferon and/or ribavirin but did not achieve sustained virological response (SVR). Genotype 1b was detected in 14 patients, genotype 1a in 4 patients, and genotype 1 in 2 patients. Patients were treated with ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) and dasabuvir (DSV) or ribavirin (RBV) for 12 or 24 weeks. Two patients were cirrhotic and had a Child-Pugh score of A. Treatment was discontinued in 2 patients due to thrombus formation in the arteriovenous fistula in the first month of DAAs treatment. SVR12 was evaluated in 14 of 18 patients and found to be 100%. One of the ten patients accepted as SVR24 had a relapse. This rate of SVR24 was similar to that in the general population.
Conclusions Our results supported that the OBV/PTV/r and DSV or RBV regimen was a safe and effective therapy for hemodialysis patients with chronic hepatitis C virus genotype 1.
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Lee SK, Lee SW, Lee HL, Kim HY, Kim CW, Song DS, Chang UI, Yang JM, Yoo SH, Kwon JH, Nam SW, Kim SH, Song MJ, Lee J, Yang H, Bae SH, Han JW, Nam H, Sung PS, Jang JW, Choi JY, Yoon SK. Real-life experience of ledipasvir and sofosbuvir for HCV infected Korean patients: a multicenter cohort study. Korean J Intern Med 2022; 37:1167-1175. [PMID: 35618302 PMCID: PMC9666263 DOI: 10.3904/kjim.2022.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 04/20/2022] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND/AIMS To evaluate the efficacy and safety of ledipasvir/sofosbuvir (LDV/SOF) therapy in hepatitis C virus (HCV)-infected Korean patients in a real clinical setting. METHODS A total of 273 patients who received LDV/SOF therapy between May 2016 and February 2021 were consecutively enrolled and analyzed. A per-protocol analysis was performed to evaluate the virologic response. RESULTS Seventy-five percent were infected with genotype 1, and 25% were infected with genotype 2. A hundred eightyone (66.3%) patients had chronic hepatitis, 74 (27.1%) had compensated cirrhosis, eight (2.9%) had decompensated cirrhosis, and 10 (3.7%) had undergone liver transplantation. Undetectable HCV RNA at week 4 was achieved in 90.2% (231/256) of patients, 99.2% (250/252) achieved the end of treatment response, and 98.1% (202/206) achieved sustained virologic response at 12 weeks post-treatment (SVR12). According to liver function, the SVR12 rates were 99.3% (135/136) in chronic hepatitis, 96.4% (53/55) in compensated cirrhosis, and 100% (6/6) in decompensated cirrhosis. The SVR12 rates according to the genotype were 98.2% (167/170) for genotype 1 and 97.2% (35/36) for genotype 2. An 8-week LDV/SOF treatment in treatment-naïve chronic hepatitis patients with HCV RNA < 6,000,000 IU/mL at baseline resulted in 100% (23/23) SVR12 rates. Overall, LDV/SOF was tolerated well, with a 0.7% (2/273) discontinuation rate due to adverse events that were unrelated to LDV/SOF. CONCLUSION LDV/SOF is effective and safe for treating HCV-infected Korean patients with high SVR12 rates.
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Affiliation(s)
- Soon Kyu Lee
- Division of Hepatology, Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Sung Won Lee
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon,
Korea
| | - Hae Lim Lee
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon,
Korea
| | - Hee Yeon Kim
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon,
Korea
| | - Chang Wook Kim
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu,
Korea
| | - Do Seon Song
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon,
Korea
| | - U Im Chang
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon,
Korea
| | - Jin Mo Yang
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon,
Korea
| | - Sun Hong Yoo
- Division of Hepatology, Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Jung Hyun Kwon
- Division of Hepatology, Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Soon Woo Nam
- Division of Hepatology, Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Seok-Hwan Kim
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon,
Korea
| | - Myeong Jun Song
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon,
Korea
| | - Jaejun Lee
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Hyun Yang
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Si Hyun Bae
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Ji Won Han
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Heechul Nam
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu,
Korea
| | - Pil Soo Sung
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Jeong Won Jang
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Jong Young Choi
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Seung Kew Yoon
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
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18
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Documento de información y consenso para la detección y manejo de la enfermedad renal crónica. Nefrologia 2022. [DOI: 10.1016/j.nefro.2021.07.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
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García-Maset R, Bover J, Segura de la Morena J, Goicoechea Diezhandino M, Cebollada Del Hoyo J, Escalada San Martin J, Fácila Rubio L, Gamarra Ortiz J, García-Donaire JA, García-Matarín L, Gràcia Garcia S, Isabel Gutiérrez Pérez M, Hernández Moreno J, Mazón Ramos P, Montañés Bermudez R, Muñoz Torres M, de Pablos-Velasco P, Pérez-Maraver M, Suárez Fernández C, Tranche Iparraguirre S, Luis Górriz J. Information and consensus document for the detection and management of chronic kidney disease. Nefrologia 2022; 42:233-264. [PMID: 36210616 DOI: 10.1016/j.nefroe.2022.07.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 07/20/2021] [Indexed: 06/16/2023] Open
Abstract
Chronic kidney disease (CKD) is a major public health problem worldwide that affects more than 10% of the Spanish population. CKD is associated with high comorbidity rates, poor prognosis and major consumption of health system resources. Since the publication of the last consensus document on CKD seven years ago, little evidence has emerged and few clinical trials on new diagnostic and treatment strategies in CKD have been conducted, apart from new trials in diabetic kidney disease. Therefore, CKD international guidelines have not been recently updated. The rigidity and conservative attitude of the guidelines should not prevent the publication of updates in knowledge about certain matters that may be key in detecting CKD and managing patients with this disease. This document, also prepared by 10 scientific associations, provides an update on concepts, clarifications, diagnostic criteria, remission strategies and new treatment options. The evidence and the main studies published on these aspects of CKD have been reviewed. This should be considered more as an information document on CKD. It includes an update on CKD detection, risk factors and screening; a definition of renal progression; an update of remission criteria with new suggestions in the older population; CKD monitoring and prevention strategies; management of associated comorbidities, particularly in diabetes mellitus; roles of the Primary Care physician in CKD management; and what not to do in Nephrology. The aim of the document is to serve as an aid in the multidisciplinary management of the patient with CKD based on current recommendations and knowledge.
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Affiliation(s)
| | | | - Julián Segura de la Morena
- Sociedad Española de Hipertensión-Liga Española para la Lucha contra la Hipertensión Arterial (SEH-LELHA)
| | | | | | | | | | | | - Jose A García-Donaire
- Sociedad Española de Hipertensión-Liga Española para la Lucha contra la Hipertensión Arterial (SEH-LELHA)
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20
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Ji Q, Chu X, Zhou Y, Liu X, Zhao W, Ye W. Safety and efficacy of grazoprevir/elbasvir in the treatment of acute hepatitis C in hemodialysis patients. J Med Virol 2022; 94:675-682. [PMID: 34599755 PMCID: PMC9298284 DOI: 10.1002/jmv.27374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 09/07/2021] [Accepted: 09/30/2021] [Indexed: 11/18/2022]
Abstract
Treatment of hepatitis C virus (HCV) infection with direct-acting antiviral agents (DAAs) in hemodialysis patients requires extensive consideration. At present, studies regarding DAAs for acute HCV infection in such patients are limited. The present study aims to evaluate the efficacy and safety of grazoprevir (GZR) plus elbasvir (EBR) treatment in acute hepatitis C (AHC) patients undergoing hemodialysis. Patients undergoing hemodialysis who had a nosocomial acute HCV infection were enrolled. All patients received GZR 100 mg/EBR 50 mg once daily for 12 weeks and were followed up for 12 weeks. Serum alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and HCV RNA levels were monitored during treatment and follow-up periods. Sustained virologic response at 12 weeks after treatment cessation and treatment-emergent adverse events (AEs) were assessed. A total of 68 AHC patients were enrolled. All patients were infected with HCV genotype 1b and achieved SVR12. Decreasing ALT, AST, and TBIL were observed over time in the first 4 weeks and became steady thereafter. Forty-eight (70.59%) patients reported at least one AEs. The most common AEs were fatigue, headache, and nausea. Two AHC patients discontinued treatment due to serious but drug-unrelated AEs. In conclusion, GZR/EBR has a high efficacy and safety profile in hemodialysis-dependent patients with genotype 1b AHC.
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Affiliation(s)
- Qinghua Ji
- Department of Infectious Disease, School of MedicineSoutheast UniversityNanjingJiangsuChina
| | - Xudong Chu
- Department of Infectious DiseasesThe Affiliated Dongtai Hospital of Nantong UniversityDongtaiJiangsuChina
| | - Yugui Zhou
- Department of Clinical LaboratoryThe Affiliated Dongtai Hospital of Nantong UniversityDongtaiJiangsuChina
| | - Xuan Liu
- Department of Clinical LaboratoryThe Second Hospital of NanjingNanjingJiangsuChina
| | - Wei Zhao
- Department of Infectious Disease, School of MedicineSoutheast UniversityNanjingJiangsuChina
| | - Wei Ye
- Department of Liver DiseaseThe Second Hospital of Nanjing, Southeast UniversityNanjingJiangsuChina
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21
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Abstract
In the 1970s, an unknown virus was suspected for documented cases of transfusion-associated hepatitis, a phenomenon called non-A, non-B hepatitis. In 1989, the infectious transmissible agent was identified and named hepatitis C virus (HCV) and, soon enough, the first diagnostic HCV antibody test was developed, which led to a dramatic decrease in new infections. Today, HCV infection remains a global health burden and a major cause of liver cirrhosis, hepatocellular carcinoma and liver transplantation. However, tremendous advances have been made over the decades, and HCV became the first curable, chronic viral infection. The introduction of direct antiviral agents revolutionized antiviral treatment, leading to viral eradication in more than 98% of all patients infected with HCV. This Perspective discusses the history of HCV research, which reads like a role model for successful translational research: starting from a clinical observation, specific therapeutic agents were developed, which finally were implemented in national and global elimination programmes.
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Affiliation(s)
- Michael P. Manns
- grid.10423.340000 0000 9529 9877Hannover Medical School, Hannover, Germany
| | - Benjamin Maasoumy
- grid.10423.340000 0000 9529 9877Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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Fabrizi F, Cerutti R, Messa P. An Updated View on the Antiviral Therapy of Hepatitis C in Chronic Kidney Disease. Pathogens 2021; 10:1381. [PMID: 34832537 PMCID: PMC8619857 DOI: 10.3390/pathogens10111381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 10/18/2021] [Accepted: 10/21/2021] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Hepatitis C virus infection remains common in patients with chronic kidney disease, including those on maintenance dialysis. The relationship between hepatitis C virus infection and chronic kidney disease is bi-directional; in fact, HCV is both a cause and consequence of chronic kidney disease. According to a systematic review with meta-analysis of observational studies (n = 23 studies) (n = 574,081 patients on long-term dialysis), anti-HCV positive serologic status was an independent and significant risk factor for death in patients with advanced chronic kidney disease on long-term dialysis. The overall estimate for adjusted mortality (all-cause death risk) with HCV was 1.26 (95% CI, 1.18; 1.34) (p < 0.0001). Interferon-based therapies are biased by low efficacy/safety in chronic kidney disease, but the advent of direct-acting antiviral drugs has made a paradigm shift in the treatment of HCV-infection. These medications give interruption of viral replication because they target specific non-structural viral proteins; four classes of DAAs exist-NS3/4A protease inhibitors, NS5A inhibitors, NS5B nucleoside and non-nucleoside polymerase inhibitors. All-oral, interferon-free, ribavirin-free combinations of DAAs are now available. AIM The goal of this narrative review is to report the available treatment options for HCV in advanced chronic kidney disease. METHODS We have made an extensive review of the medical literature and various research engines have been adopted. RESULTS Some combinations of DAAs are currently recommended for HCV in advanced CKD (including patients on maintenance dialysis): elbasvir/grazoprevir; glecaprevir/pibrentasvir; and sofosbuvir-based regimens. Solid evidence, based on registration and "real life" studies supports their efficacy (SVR rates > 90%) and safety even in patients with advanced CKD. No dosage adjustment is necessary and treatment duration is 8-12 weeks. However, recent data highlight that many patients with advanced CKD remain untreated, and numerous barriers to antiviral treatment of HCV still exist. Whether successful antiviral therapy with DAAs will translate into improved survival in the advanced CKD population is another point of future research.
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Affiliation(s)
- Fabrizio Fabrizi
- Division of Nephrology, Dialysis, and Kidney Transplant, Ca’ Granda IRCCS Foundation and Maggiore Policlinico Hospital, 20122 Milano, Italy; (R.C.); (P.M.)
| | - Roberta Cerutti
- Division of Nephrology, Dialysis, and Kidney Transplant, Ca’ Granda IRCCS Foundation and Maggiore Policlinico Hospital, 20122 Milano, Italy; (R.C.); (P.M.)
| | - Piergiorgio Messa
- Division of Nephrology, Dialysis, and Kidney Transplant, Ca’ Granda IRCCS Foundation and Maggiore Policlinico Hospital, 20122 Milano, Italy; (R.C.); (P.M.)
- Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
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Ali S, Ur-Rehman T, Ali M, Haque S, Rasheed F, Lougher E, Nawaz MS, Paudyal V. Improving access to the treatment of hepatitis C in low- and middle-income countries: evaluation of a patient assistance programme. Int J Clin Pharm 2021; 43:958-968. [PMID: 33247820 PMCID: PMC8352841 DOI: 10.1007/s11096-020-01202-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Accepted: 11/12/2020] [Indexed: 12/15/2022]
Abstract
Background Modern antiviral treatments have high cure rates against the hepatitis C virus however, the high cost associated with branded medicines and diagnostic tests, have resulted in poor access for many low-income patients residing in low-and-middle-income countries. Objective This study aimed to evaluate the role of a patient assistance programme and generic medicines in improving access to treatment of low-income hepatitis C patients in a low-and-middle-income country. Setting A major teaching public hospital in Islamabad, Pakistan. Methods Hepatitis C patients who presented and enrolled for the patient assistance programme during 12 months (1st July 2015 and 30th June 2016) were included. Demography, prescription characteristics, the total costs of Hepatitis C treatment, medicine cost supported by the programme, out-of-pocket cost borne by the patient and average cost effectiveness ratio per sustained virologic response were calculated and compared for different generic and branded regimens. Main outcome measure cost contribution of patient assistance programme. Results A total of 349 patients initiated the treatment through the programme and of those 334 (95.7%) completed the prescribed treatment. There were 294 (88.02%) patients who achieved sustained virologic response. Patient assistance programme contributed medicines cost averaging 60.28-86.26% of the total cost of treatment ($1634.6) per patient. The mean (SE) cost per patient for generic option (Sofosbuvir/Ribavirin) was the lowest [$658.36 (22.3) per patient, average cost effectiveness ratio = $720.1/SVR] than branded option (Sovaldi/Ribavirin) [$2218.66 (37.6) per patient, average cost effectiveness ratio = $2361.8/SVR] of the three available treatment regimens. From patients' perspectives, the mean (SE) out-of-pocket cost was $296.9 (6.7) which primarily included diagnostic cost (69.9%) of the total cost. Conclusions Patient assistance programme, combined with generic brands of newer hepatitis C treatment offered a significant reduction in cost and widens access to hepatitis C treatment in low-and middle-income countries. However, substantial out-of-pocket costs of the treatment presents an important barrier for service access. There is a scope to widen such financial assistance programme to offer other costs attributed to patients, specifically for diagnosis, to widen service use in low-and-middle-income countries.
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Affiliation(s)
- Salamat Ali
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan
| | - Tofeeq Ur-Rehman
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan
| | - Mashhood Ali
- Department of Gastroenterology, Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan
| | - Sayeed Haque
- Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Faisal Rasheed
- UBT Laboratory, Nuclear Medicines, Oncology and Radiotherapy Institute, Islamabad, Pakistan
| | - Eleri Lougher
- Abertawe Bro Morgannwg University Health Board, Princess of Wales Hospital, Bridgend, UK
| | | | - Vibhu Paudyal
- School of Pharmacy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
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Suda G, Sakamoto N. Recent advances in the treatment of hepatitis C virus infection for special populations and remaining problems. J Gastroenterol Hepatol 2021; 36:1152-1158. [PMID: 32667068 DOI: 10.1111/jgh.15189] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 07/02/2020] [Accepted: 07/12/2020] [Indexed: 12/16/2022]
Abstract
Hepatitis C virus (HCV) infection is one of the primary causes of liver cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation (LT). The rate of HCV infection is high in patients on hemodialysis and in patients infected with human immunodeficiency virus (HIV). In liver transplant patients with HCV infection, recurrent HCV infection of the transplanted liver is universal and results in rapid liver fibrosis progression. In patients with HCV/HIV coinfection as well, liver fibrosis advances rapidly. Thus, there is an urgent need for prompt HCV infection treatment in these special populations (i.e. HIV/HCV coinfection, HCV infection after LT, and dialysis patients). Interferon (IFN)-based therapy for HCV infection could not achieve a high rate of sustained viral response and could cause severe adverse events in the aforementioned special populations. Direct-acting antivirals (DAAs) have recently been developed, and clinical trials have shown that IFN-free DAA-based therapies are associated with a significantly better safety and therapeutic profile than IFN-based therapies. However, the majority of the initial DAA trials excluded special populations; thus, the efficacy and safety of IFN-free DAA-based therapy in special populations remained to be clearly established. Although recent clinical trials and clinical studies have shown the high efficacy and safety of this therapy even in special populations, several unresolved problems, including emergence of resistance-associated variants after failure to respond to DAAs and HCC occurrence after DAA therapy, still exist. Hence, in this review, we discuss the recent advances in anti-HCV therapy for special populations and the remaining problems regarding this therapy.
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Affiliation(s)
- Goki Suda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
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25
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Teama NM, Abdel-Mohsen WA, Ahmed OA, El Sayed SM, ElGhandour AM. Effectiveness and safety of ombitasvir/paritaprevir/ritonavir in treatment of chronic hepatitis C Egyptian hemodialysis patients, case-control study. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00079-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Abstract
Background
Prevalence of hepatitis C virus infection in patients with renal diseases is higher compared to the general population. FDA has approved ombitasvir/paritaprevir/ ritonavir for the treatment of patients with severe renal disease. This study aimed to evaluate the efficacy and safety of ombitasvir/paritaprevir/ritonavir with or without ribavirin in treatment of chronic hepatitis C Egyptian hemodialysis patients to compare it with the same treatment result in chronic hepatitis C Egyptian patients with normal renal functions. This case-control study was conducted on one hundred patients with confirmed diagnosis of HCV-positive infection at the Center of National Committee for Control of Viral Hepatitis [NCCVH] at Ain Shams University Hospital. Patients were divided into two groups: group I (control group) with 50 chronic hepatitis C virus patients with normal renal functions and group II (Case Group) with 50 chronic hepatitis C virus hemodialysis patients.
Results
95.1% of prevalent hemodialysis patients achieved sustained virological response (SVR), while 100% of patients with normal kidney functions achieved sustained virological response. Most common side effects were hemoglobin drop, gastrointestinal disturbance, severe fatigue, and itching.
Conclusion
Ombitasvir, paritaprevir, and ritonavir are considered a safe and effective in treatment in HCV infection in patients on regular hemodialysis as in chronic hepatitis C virus infection patients with normal kidney functions.
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26
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The effect of anemia on the efficacy and safety of treating chronic hepatitis C infection with direct-acting antivirals in patients with chronic kidney disease. Int Urol Nephrol 2020; 53:749-761. [PMID: 33111161 DOI: 10.1007/s11255-020-02656-y] [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: 04/28/2020] [Accepted: 09/14/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND/AIM Chronic hepatitis-C infection is a great health burden in Egypt. The effect of anemia on the efficacy and safety of direct-acting anti-viral (DAA) therapies for those with chronic-kidney disease (CKD) has not been evaluated. PATIENTS/METHODS This single-center retrospective study included 235 renal patients: i.e., 70-CKD patients not on hemodialysis (42 with anemia, 28 without); 40 hemodialysis patients (16 anemic; 24 non-anemic), and 125 kidney-transplant (KTx) recipients (40 anemic; 85 non-anemic). Anemia was defined by a hemoglobin level < 10.5 g/dL. Hemodialysis patients received ritonavir-boosted paritaprevir/ombitasvir. KTx patients received sofosbuvir/daclatasvir. CKD patients with eGFR > 30 mL/min/1.73 m2 received sofosbuvir/daclatasvir. Those with eGFR < 30 mL/min/1.73 m2 received ritonavir-boosted paritaprevir/ombitasvir; 64 non-anemic patients also received ribavirin therapy. RESULTS Mean age of CKDs was 49.1 years, 43.2 years for HDs, and 45.2 years for KTx patients. Most were male; body-mass index was ~ 23.8. Anemia did not affect the efficacy of DAAs in hemodialysis, CKD, or KTx patients. Most patients achieved a rapid virologic response (RVR), and a 12- and 24-week sustained viral response. Worsening of anemia among the non-anemic group was mostly related to ribavirin therapy in hemodialysis patients (11/16 patients). Acute kidney injury in CKDs occurred more frequently within the anemic group (59.5%) compared to the non-anemic group (32.1%). For KTx, graft impairment was more common among the anemic group (7/40) compared to the non-anemic group (2/85). CONCLUSION Hemoglobin levels of < 10.5 g/dL prior to DAA treatment did not affect the virological response in renal patients but was associated with increased serum creatinine among KTx and those with CKD.
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Abd-Elsalam S, Abo-Amer YEE, El-Abgeegy M, Elshweikh SA, Elsergany HF, Ahmed R, Elkadeem M, Hawash N, Soliman S, Badawi R, Elguindy AMA, Soliman MY, Mohmed AA, Mansour L. Efficacy and safety of ombitasvir/paritaprevir/ritonavir/ribavirin in management of Egyptian chronic hepatitis C virus patients with chronic kidney disease: A real-life experience. Medicine (Baltimore) 2020; 99:e21972. [PMID: 33080669 PMCID: PMC7572016 DOI: 10.1097/md.0000000000021972] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease was difficult in the past because of the use of interferon (IFN). It was associated with high risk IFN-related adverse reactions due to reduced renal clearance of IFN. This study aimed to evaluate the antiviral efficacy, safety, and tolerability of ombitasvir/paritaprevir/ritonavir/ribavirin in chronic kidney disease patients infected with chronic HCV.This observational, open-label prospective study was carried out on 103 patients infected chronic HCV with different grades of renal impairment. Paritaprevir/ritonavir and ombitasvir (75/50/12.5 mg) twice daily plus ribavirin were given to the patients for 12 weeks. Dose adjustment of ribavirin was done according to degree of renal impairment.Sustained virological response (12 weeks after the end of treatment) occurred in 101 patients (98.1%). Anemia occurred in 48 patients. No serious adverse events were observed in any patient.Paritaprevir/ritonavir and ombitasvir plus ribavirin for 12 weeks was considered to be safe and effective in the treatment of chronic HCV infected patients with varying degrees of renal impairment.
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Affiliation(s)
- Sherief Abd-Elsalam
- Department of Tropical Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Yousry Esam-Eldin Abo-Amer
- Hepatology, Gastroenterology and Infectious Diseases Department, Mahala Hepatology Teaching Hospital, Gharbia
| | - Mohamed El-Abgeegy
- National Hepatology and Tropical Medicine Research Institute in Cairo, Cairo, Egypt
| | | | - Heba Fadl Elsergany
- National Hepatology and Tropical Medicine Research Institute in Cairo, Cairo, Egypt
| | - Rehab Ahmed
- National Hepatology and Tropical Medicine Research Institute in Cairo, Cairo, Egypt
| | - Mahmoud Elkadeem
- Department of Tropical Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Nehad Hawash
- Department of Tropical Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Shaimaa Soliman
- Department of Public health and Community medicine, Menofia University, Menofia, Egypt
| | - Rehab Badawi
- Department of Tropical Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt
| | | | - Moataz Yousry Soliman
- Hepatology, Gastroenterology and Infectious Diseases Department, Mahala Hepatology Teaching Hospital, Gharbia
| | | | - Loai Mansour
- Department of Tropical Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt
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Farouk F, Wahba D, Mogawer S, Elkholy S, Elmeligui A, Abdelghani R, Ibahim S. Development and Validation of a New LC-MS/MS Analytical Method for Direct-Acting Antivirals and Its Application in End-Stage Renal Disease Patients. Eur J Drug Metab Pharmacokinet 2020; 45:89-99. [PMID: 31667795 DOI: 10.1007/s13318-019-00584-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND OBJECTIVE The effectiveness of direct-acting antivirals (DAAs) is not well established in end-stage renal disease (ESRD) patients. Assessment of the plasma concentrations may support understanding of their therapeutic outcomes in this population. The aim of this study is to develop a direct, yet matrix-effect tolerant, analytical method for determining DAAs in the plasma of ESRD patients while maintaining a moderate cost per sample and with an improved analyte extraction recovery. METHODS In this study, a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the analysis of ombitasvir (OMB), paritaprevir (PRT) and ritonavir (RIT) in plasma. Sample preparation was performed using the liquid-liquid extraction (LLE) method. Isocratic separation was performed using a mixture of methanol and 10 mM ammonium acetate (79:21, v/v) followed by MS/MS detection. The method was validated and applied to determine DAAs in the plasma of ESRD patients (n = 7). RESULTS The developed method was linear (r2 > 0.995), accurate (89.4 ± 7.8 to 108.3 ± 3.0) and precise (% CV 0.9-15.0) and showed improved recovery (> 80) over previously published ones in the range 5-250, 30-1,500, 20-1,000 ng/mL for OMB, PRT and RIT, respectively. Relative matrix effect was absent, and the method accurately determined the three DAAs in real-life samples (n = 7). CONCLUSIONS An efficient analytical method for the determination of DAAs is presented. The method overcomes the potential analytical response fluctuation in ESRD. The developed method show improved extraction recoveries and is suitable for routine application in developing economies where hepatitis C virus is most prevalent.
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Affiliation(s)
- Faten Farouk
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6th October City, Egypt.
| | - Dina Wahba
- National Organization of Drug Quality Control and Research, Giza, Egypt
| | - Sherif Mogawer
- Internal Medicine Department, Hepato-gastroenterology Unit, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Shaimaa Elkholy
- Internal Medicine Department, Hepato-gastroenterology Unit, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Ahmed Elmeligui
- Internal Medicine Department, Hepato-gastroenterology Unit, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Reham Abdelghani
- Internal Medicine Department, Nephrology Unit, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Salwa Ibahim
- Internal Medicine Department, Nephrology Unit, Faculty of Medicine, Cairo University, Giza, Egypt
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Abstract
INTRODUCTION Hepatitis C virus (HCV) infection is associated with an increased incidence and progression of chronic kidney disease (CKD), as well as higher mortality in CKD and renal transplant patients. Direct acting antiviral agents (DAAs) have revolutionized the treatment of HCV, with viral eradication attained in 90-100% of treated patients. DAAs have an excellent safety and tolerability profile in CKD and renal transplant patients. AREAS COVERED In this review, we discuss the association of HCV with incidence and progression of CKD as well as its effect on outcomes and mortality. We also discuss the available treatment options in patients with CKD and renal transplant and in HCV-associated glomerular disease. EXPERT OPINION The availability of newly available direct acting anti-viral agents has revolutionized the treatment of HCV in persons with advanced CKD and undergoing dialysis. With these regimens, viral eradication can be attained in 90-100% of the treated patients. The safety, tolerability, and efficacy of these drugs in renal transplant patients have also made it possible to use HCV-infected grafts and successful virus eradication at a later stage.
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Affiliation(s)
- Muhammad Umair Khan
- Department of Medicine, Division of Gastroenterology, Hamad Medical Corporation , Doha, Qatar
| | - Mohamed Ibrahim Mahmoud
- Department of Medicine, Division of Gastroenterology, Hamad Medical Corporation , Doha, Qatar
| | - Adeel A Butt
- Weill Cornell Medical College , New York, Qatar.,Department of Medicine, Hamad Medical Corporation , Doha, Qatar
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Yu ML, Chen PJ, Dai CY, Hu TH, Huang CF, Huang YH, Hung CH, Lin CY, Liu CH, Liu CJ, Peng CY, Lin HC, Kao JH, Chuang WL. 2020 Taiwan consensus statement on the management of hepatitis C: Part (II) special populations. J Formos Med Assoc 2020; 119:1135-1157. [PMID: 32354689 DOI: 10.1016/j.jfma.2020.04.002] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 04/05/2020] [Indexed: 12/13/2022] Open
Abstract
Hepatitis C virus (HCV) infection is a silent killer that leads to rapid progression of liver cirrhosis and hepatocellular carcinoma (HCC). High prevalence of HCV infection has been reported in Taiwan, especially in high-risk populations including people who inject drugs (PWID) and patients requiring dialysis. Besides, certain populations merit special considerations due to suboptimal outcome, potential drug-drug interaction, or possible side effect. Therefore, in the second part of this 2-part consensus, the Taiwan Association for the Study of the Liver (TASL) proposes the treatment recommendations for the special population in order to serve as guidance to optimizing the outcome in the direct-acting antiviral (DAA) era. Special populations include patients with acute or recent HCV infection, previous DAA failure, chronic kidney disease, decompensated cirrhosis, HCC, liver and other solid organ transplantations, receiving an HCV viremic organ, hepatitis B virus (HBV) and HCV dual infection, HCV and human immunodeficiency virus (HIV) coinfection, active tuberculosis infection, PWID, bleeding disorders and hemoglobinopathies, children and adolescents, and pregnancy. Moreover, future perspectives regarding the management of hepatitis C are also discussed and summarized in this consensus statement.
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Affiliation(s)
- Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Pei-Jer Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
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Castellote J, Gea F, Morano LE, Morillas RM, Pineda JA, Vergara M, Buti M. Factors influencing hepatitis C cure in the era of direct-acting antivirals. GASTROENTEROLOGIA Y HEPATOLOGIA 2020; 42 Suppl 1:1-7. [PMID: 32560767 DOI: 10.1016/s0210-5705(20)30181-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Direct-acting antiviral agents are highly potent drugs with a strong genetic barrier. Consequently, the factors influencing hepatitis C cure have been reduced and have progressively lost importance. Host factors, such as the presence of cirrhosis, race, and treatment adherence, influence sustained viral response. Adherence, together with treatment errors and drug interactions, are also important, especially in older patients. Viral factors, such as viral load, genotype, and the presence of baseline resistances affect the response rate but their influence can be minimised by using pan-genotypic regimens. Treatment simplification and the high efficacy of new antiviral treatments will allow treatment universalisation and will hopefully enable elimination of the infection in the next few decades. Supplement information: This article is part of a supplement entitled "The value of simplicity in hepatitis C treatment", which is sponsored by Gilead. © 2019 Elsevier España, S.L.U. All rights reserved.
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Affiliation(s)
- José Castellote
- Servicio de Aparato Digestivo, Hospital Universitari de Bellvitge, IDIBELL, L'Hospitalet de Llobregat, Barcelona, España.; Universitat de Barcelona, Barcelona, España.
| | - Francisco Gea
- Unidad de Sistema Digestivo, Hospital Universitario Ramón y Cajal, Madrid, España
| | - Luis Enrique Morano
- Unidad de Patologías Infecciosas, Hospital Universitario Álvaro Cunqueiro, Vigo, Pontevedra, España
| | - Rosa M Morillas
- Servicio de Aparato Digestivo, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, España; CIBEREHD, Instituto Carlos III, Madrid, España
| | - Juan Antonio Pineda
- Unidad de Enfermedades Infecciosas y Microbiología, Hospital Nuestra Señora de Valme, Sevilla, España
| | - Mercedes Vergara
- CIBEREHD, Instituto Carlos III, Madrid, España; Unidad de Hepatología, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Barcelona, España
| | - María Buti
- Unidad de Hepatología, Hospital General Universitario Vall d'Hebron, Barcelona, España
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Lawitz E, Landis CS, Flamm SL, Bonacini M, Ortiz-Lasanta G, Huang J, Zhang J, Kirby BJ, De-Oertel S, Hyland RH, Osinusi AO, Brainard DM, Robson R, Maliakkal BJ, Gordon SC, Gane EJ. Sofosbuvir plus ribavirin and sofosbuvir plus ledipasvir in patients with genotype 1 or 3 hepatitis C virus and severe renal impairment: a multicentre, phase 2b, non-randomised, open-label study. Lancet Gastroenterol Hepatol 2020; 5:918-926. [PMID: 32531259 DOI: 10.1016/s2468-1253(19)30417-0] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Revised: 10/24/2019] [Accepted: 11/05/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND There is a medical need for highly effective, safe, and well tolerated treatments for patients infected with hepatitis C virus (HCV) with severe renal impairment. We investigated the safety and efficacy of sofosbuvir with ribavirin or ledipasvir combined with sofosbuvir in a prospective study of patients with genotype 1 or 3 HCV infection and stage 4-5 chronic kidney disease (creatinine clearance by Cockcroft-Gault ≤30 mL/min) who were not on dialysis. METHODS This phase 2b, open-label, non-randomised, multicentre study in the USA and New Zealand investigated three sequentially enrolled cohorts of patients. Patients were recruited from ten hospitals and clinical research centres and were included if they had genotype 1 or 3 HCV infection, a creatinine clearance less than or equal to 30 mL/min, and were not on dialysis. In cohorts 1 and 2, patients received sofosbuvir (200 mg in cohort 1 and 400 mg in cohort 2) plus ribavirin 200 mg once per day for 24 weeks. In cohort 3, 18 patients received ledipasvir combined with sofosbuvir (90 mg ledipasvir and 400 mg sofosbuvir) once per day for 12 weeks. The primary efficacy endpoint was the proportion of patients achieving sustained virological response 12 weeks after the end of treatment (SVR12). Safety and pharmacokinetic data were also collected. The trial is registered with ClinicalTrials.gov, number NCT01958281, and is completed. FINDINGS This study was done between Oct 7, 2013, and Oct 29, 2017. In the sofosbuvir plus ribavirin cohorts, 32 patients were screened, of whom 20 were enrolled and assessed for efficacy and safety (ten patients in each cohort). In the ledipasvir plus sofosbuvir cohort, 33 patients were screened, of whom 18 were enrolled and assessed for treatment efficacy and safety. Four (40%, 95% CI 12-74) of ten patients in cohort 1 and six (60%, 26-88) of ten patients in cohort 2 achieved SVR12. All 18 (100%, 82-100) patients in cohort 3 achieved SVR12. Adverse events were mostly mild or moderate in severity. The most commonly reported adverse events overall were headache (eight [21%] of 38 patients), anaemia (seven [18%] of 38 patients), and fatigue (six [16%] of 38 patients). Eight patients had serious adverse events, none of which were treatment related. There were no treatment-related cardiac events or clinically significant changes in echocardiographic parameters or creatinine clearance by Cockcroft-Gault. INTERPRETATION In this phase 2b study, ledipasvir combined with sofosbuvir for 12 weeks was safe and effective in patients with genotype 1 HCV infection and stage 4-5 chronic kidney disease who were not on dialysis. FUNDING Gilead Sciences.
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Affiliation(s)
- Eric Lawitz
- Texas Liver Institute, University of Texas Health San Antonio, San Antonio, TX, USA
| | - Charles S Landis
- Department of Medicine, University of Washington, Seattle, WA, USA
| | | | - Maurizio Bonacini
- Mission Gastroenterology and Hepatology, University of California, San Francisco, CA, USA
| | | | | | - Jie Zhang
- Gilead Sciences, Foster City, CA, USA
| | | | | | | | | | | | - Richard Robson
- Christchurch Clinical Studies Trust, Christchurch, New Zealand
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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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34
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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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35
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Debnath P, Chandnani S, Rathi P, Nair S, Pawar V, Contractor Q. COMBINED NS5A & NS5B NUCLEOTIDE INHIBITOR THERAPY FOR PATIENTS WITH CHRONIC HEPATITIS C WITH STAGE 5 CHRONIC KIDNEY DISEASE ON HEMODIALYSIS. ARQUIVOS DE GASTROENTEROLOGIA 2020; 57:39-44. [PMID: 32294734 DOI: 10.1590/s0004-2803.202000000-08] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 11/28/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is the most common hepatotropic viral infection affecting the patients on maintenance hemodialysis. Treatment of chronic HCV infection in stage 4 and 5 CKD includes a combination of elbasvir/grazoprevir and glecaprevir/pibrentasvir, which are not available in many countries. OBJECTIVE Hence, we have conducted this study to look for the safety and efficacy of sofosbuvir combination therapy in this difficult to treat population. METHODS We conducted a single-center, prospective, open-label study in which Stage 5 CKD patients on maintenance hemodialysis with HCV infection. Total of 18 patients was included. sofosbuvir with daclatasvir or ledipasvir was used according to genotype for 12 weeks. HCV RNA, genotype, transient elastography (TE) was considered for every patient. HCV RNA was quantified at 4th week, 12th week and 12 weeks post-treatment to look for sustained virologic response (SVR 12). RESULTS Infection due to genotype 1 was seen in 12 (66.7%) patients followed by genotype 3 in 4 (22.3%) with each patient of genotype 2 and 5. The median value of HCV RNA was 2,35,000 IU/mL. On TE, all had liver stiffness of <9.4 KPa. All patients had HCV RNA of <15 IU/mL at 4th and 12th week of treatment and 12 weeks post-treatment. No significant change in hemoglobin, eGFR and liver stiffness was observed. CONCLUSION Full dose sofosbuvir i.e. 400 mg, in combination with NS5A inhibitors daclatasvir or ledipasvir is found to be safe and effective in patients with end stage renal disease, who are on maintenance hemodialysis.
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Affiliation(s)
- Prasanta Debnath
- T.N.M.C & B.Y.L Nair Charitable Hospital, Gastroenterology, Mumbai, India
| | - Sanjay Chandnani
- T.N.M.C & B.Y.L Nair Charitable Hospital, Gastroenterology, Mumbai, India
| | - Pravin Rathi
- T.N.M.C & B.Y.L Nair Charitable Hospital, Gastroenterology, Mumbai, India
| | - Sujit Nair
- T.N.M.C & B.Y.L Nair Charitable Hospital, Gastroenterology, Mumbai, India
| | - Vinay Pawar
- T.N.M.C & B.Y.L Nair Charitable Hospital, Gastroenterology, Mumbai, India
| | - Qais Contractor
- T.N.M.C & B.Y.L Nair Charitable Hospital, Gastroenterology, Mumbai, India
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Roth D, Bloom RD, Molnar MZ, Reese PP, Sawinski D, Sise ME, Terrault NA. KDOQI US Commentary on the 2018 KDIGO Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C. Am J Kidney Dis 2020; 75:665-683. [PMID: 32279907 DOI: 10.1053/j.ajkd.2019.12.016] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 12/20/2019] [Indexed: 02/06/2023]
Abstract
The first KDIGO (Kidney Disease: Improving Global Outcomes) guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection was published in 2008. The ensuing decade bore witness to remarkable advances in the treatment of HCV infection following the approval of direct-acting antiviral (DAA) agents that deliver cure rates routinely >95%. In this context, the KDIGO organization correctly recognized the need for an updated HCV guideline that would be relevant to the treatment of HCV-infected patients with kidney disease in the DAA era. The current NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) commentary provides an in-depth review and perspective on the 2018 KDIGO guideline. Of note, the KDIGO work group made significant updates to guideline chapters 2 and 4 as a direct result of the availability of DAAs. The intent of this commentary is to provide useful interpretation for nephrologists and other practitioners caring for HCV-infected patients with chronic kidney disease, including dialysis patients and kidney transplant recipients. The availability of DAA agents that are safe and highly effective has created new opportunities, such as the transplantation of kidneys from HCV-infected kidney donors. The ability to treat HCV infection in patients with kidney disease will have a significant impact on the care of our patients and should favorably influence long-term outcomes as well.
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Affiliation(s)
- David Roth
- Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, FL.
| | - Roy D Bloom
- Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Kidney and Pancreas Transplant Program, Penn Transplant Institute, Philadelphia, PA
| | - Miklos Z Molnar
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, TN; Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, TN; Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN; Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary
| | - Peter P Reese
- Renal-Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA
| | - Deirdre Sawinski
- Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Meghan E Sise
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA
| | - Norah A Terrault
- Keck School of Medicine, University of Southern California, Los Angeles, CA
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Yang H, Hu X, Pu L, Ren S, Feng Y. Efficacy and safety of direct-acting antiviral-based treatment in hepatitis C virus infected patients with chronic renal function impairment: An updated systemic review and meta-analysis. Nephrology (Carlton) 2020; 25:829-838. [PMID: 32108975 DOI: 10.1111/nep.13704] [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: 09/28/2019] [Revised: 02/02/2020] [Accepted: 02/11/2020] [Indexed: 01/29/2023]
Abstract
OBJECTIVE To further determine the efficacy and safety of direct-acting antiviral (DAA)-based treatments in hepatitis C virus (HCV) infected patients with renal function impairment. METHODS MEDLINE, EMBASE and the Cochrane Library were searched for relevant studies. All studies assessing the efficacy and safety of DAA-based treatments against HCV infection in patients with renal impairment and HCV infection were eligible for inclusion. Outcomes assessed included efficacy outcomes and safety outcomes. Summary estimates were obtained using an inverse-variance weighted random effect model and Freeman-Tukey double arcsine transformation. RESULTS Twenty-seven studies (n = 1048 participants) were included. The majority of included studies were of fair quality with Newcastle-Ottawa scale scores between 4 and 6. The pooled virologic response rates at the end of treatment or 4, 12, 24 weeks after treatment (ie, EOTR, SVR4, SVR12 and SVR24 rates) were 97.0% (95% confidence interval [CI], 94.0%-99.0%), 80.9% (95% CI, 49.3%-98.7%), 94.1% (95% CI, 91.6%-96.3%) and 89.6% (95% CI, 75.5%-98.1%), respectively. The pooled relapse rate was 6.4% (95% CI, 3.4%-10.4%). The pooled incidence of adverse events and severe adverse events leading to discontinuation were 47.6% (95% CI, 35.0%-60.4%) and 2.9% (95% CI, 1.4%-5.0%), respectively. High heterogeneity among studies exists for SVR4 and SVR24 rates. Formal statistical testing did not identify the presence of publication bias for all measured outcomes except the relapse rate. CONCLUSION The results support the efficacy and safety of DAA-based treatments in this population. Future studies with better design, larger sample size and longer follow up will be the next step. SUMMARY AT A GLANCE This systematic review evaluated the efficacy and safety of direct-acting antiviral based therapies in hepatitis C infection in patients with renal impairment. The majority of studies were of fair quality only. These therapies were found to be highly efficacious although there were high rates of adverse events.
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Affiliation(s)
- Hongling Yang
- Nephrology Department, Sichuan Provincial People's Hospital, Medical school of University of Electronic Science and Technology of China, Chengdu, China.,Chinese Academy of Sciences, Sichuan Translational Medicine Research Hospital, Chengdu, China
| | - Xiao Hu
- Chinese Academy of Sciences, Sichuan Translational Medicine Research Hospital, Chengdu, China.,Gastroenterology Department, Sichuan Provincial People's Hospital, Medical school of University of Electronic Science and Technology of China, Chengdu, China
| | - Lei Pu
- Nephrology Department, Sichuan Provincial People's Hospital, Medical school of University of Electronic Science and Technology of China, Chengdu, China.,Chinese Academy of Sciences, Sichuan Translational Medicine Research Hospital, Chengdu, China
| | - Song Ren
- Nephrology Department, Sichuan Provincial People's Hospital, Medical school of University of Electronic Science and Technology of China, Chengdu, China.,Chinese Academy of Sciences, Sichuan Translational Medicine Research Hospital, Chengdu, China
| | - Yunlin Feng
- Nephrology Department, Sichuan Provincial People's Hospital, Medical school of University of Electronic Science and Technology of China, Chengdu, China.,Chinese Academy of Sciences, Sichuan Translational Medicine Research Hospital, Chengdu, China
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Tatar B, Köse Ş, Ergun NC, Turken M, Onlen Y, Yılmaz Y, Akhan S. Response to direct-acting antiviral agents in chronic hepatitis C patients with end-stage renal disease: a clinical experience. ACTA ACUST UNITED AC 2020; 65:1470-1475. [PMID: 31994628 DOI: 10.1590/1806-9282.65.12.1470] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 07/29/2019] [Indexed: 12/12/2022]
Abstract
OBJECTIVE The recent development of direct-acting antiviral agents (DAAs) has dramatically changed the treatment of chronic hepatitis C, and interferon-based regimes have become a poor treatment choice in clinical practice. Today DAAs offer shorter, well-tolerated, highly effective curative therapies. This study aimed to evaluate the effectiveness and safety of DAAs in patients with end-stage renal disease and HCV genotype 1 infection in real clinical practice. METHODS Thirty-six patients who attended our clinic, were diagnosed with chronic hepatitis C (CHC), undergoing hemodialysis, and fulfilled the criteria of age >18 years, genotype 1 infection, with a detectable HCV RNA level were considered for the study. Patients with GT1a infection received OBV/PTV/r plus DSV plus RBV for 12 weeks; GT1b infected patients received this regimen without RBV for 12 weeks. RESULTS The study was conducted on 33 patients. The mean age was 52.30 ±13.77 years, and 70 % of them were male. By the fourth week of treatment, HCV RNA levels decreased below 15 IU/ml in all patients. Sustained virologic response (SVR) 12 rate was 100%. Nine patients had side effects during treatment. Of the patients with side effects, 89.9% were in group 1a and 11.1% in group 1b. CONCLUSION In this study, treatment with OBV/PTV/r and DSV with or without RBV resulted in high rates of sustained virologic response in HCV GT1-infected patients with end-stage renal disease (ESRD). SVR was achieved in all patients with few side effects.
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Affiliation(s)
- Bengu Tatar
- . Turkiye Cumhuriyeti Saglik Bakanlıgı, Izmir Tepecik Egitim ve Arastirma Hastanesi, Infectious Diseases and Clinical Microbiology, Izmır, Turkey
| | - Şükran Köse
- . Turkiye Cumhuriyeti Saglik Bakanlıgı, Izmir Tepecik Egitim ve Arastirma Hastanesi, Infectious Diseases and Clinical Microbiology, Izmır, Turkey
| | - Nadide Colak Ergun
- . Turkiye Cumhuriyeti Saglik Bakanlıgı, Izmir Tepecik Egitim ve Arastirma Hastanesi, Infectious Diseases and Clinical Microbiology, Izmır, Turkey
| | - Melda Turken
- . Turkiye Cumhuriyeti Saglik Bakanlıgı, Izmir Tepecik Egitim ve Arastirma Hastanesi, Infectious Diseases and Clinical Microbiology, Izmır, Turkey
| | - Yusuf Onlen
- . Mustafa Kemal Universitesi, Infectious Diseases and Clinical Microbiology, Hatay, Turkey
| | - Yusuf Yılmaz
- . Marmara Universitesi, Gastroenterology, Istanbul, Turkey
| | - Sıla Akhan
- . Kocaeli Universitesi, Infectious Diseases and Clinical Microbiology, Kocaeli, Turkey
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Impact of HIV and chronic kidney disease comorbidities on hepatitis C treatment choices, drug-drug interactions and hepatitis C cure. Int J Clin Pharm 2020; 42:515-526. [PMID: 32100238 PMCID: PMC7192872 DOI: 10.1007/s11096-020-00994-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Accepted: 02/12/2020] [Indexed: 01/03/2023]
Abstract
Background Human immunodeficiency virus (HIV) co-infection and chronic kidney disease add challenges to hepatitis C virus treatment. Objective To conduct a comparative study of treatment choices, drug–drug interactions and clinical outcomes in hepatitis C mono-infected patients, or those with HIV or chronic kidney disease comorbidities. Setting Hepatitis C treatment centers of West Midlands England, United Kingdom. Method An observational study was conducted analyzing datasets of all hepatitis C patients that were referred to a large tertiary liver unit in the West Midlands, UK between July 2015 and January 2018. Patients aged ≥ 18 years with diagnosis of hepatitis C alone or co-infected with HIV or comorbid with chronic kidney disease were eligible. Main outcome measures The treatment choices, relevant potential drug–drug interactions and sustained virologic response 12 weeks post end of treatment were assessed. Results Out of 313 patients, 154 (49.2%) were hepatitis C mono-infected, 124 (39.6%) hepatitis C/HIV co-infected and 35 (11.2%) were hepatitis C/chronic kidney disease comorbid. There were 151 (98.1%) of hepatitis C mono-infected, 110 (88.7%) of hepatitis C/HIV and 20 (57.1%) of hepatitis C/chronic kidney disease patients treated with 1st line regimens. Significantly more patients who had co-morbidity with either HIV or chronic kidney disease were prescribed 2nd line regimens (8.1% and 37.1% respectively), compared to patients with hepatitis C mono-infection (1.9%) (P value < 0.05). Comorbid patients (12.1% of HIV and 25.8% of chronic kidney disease) were more likely to required drug–drug interactions advice (grade 5) than hepatitis C mono-infected (1.8%). Higher cure rates were observed in hepatitis C mono-infected (95.33%), hepatitis C/HIV (96.1%) compared to hepatitis C/chronic kidney disease patients (90.3%). Conclusion This study shows that treatment pathways permitting access to individual treatment adjustments in accordance with comorbidities and with consideration of drug–drug interaction in a multi-disciplinary team, provides successful outcomes in hepatitis C patients co-morbid with HIV or chronic kidney disease.
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Renal safety in 3264 HCV patients treated with DAA-based regimens: Results from a large Italian real-life study. Dig Liver Dis 2020; 52:190-198. [PMID: 31813755 DOI: 10.1016/j.dld.2019.11.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 11/11/2019] [Accepted: 11/12/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Sofosbuvir (SOF)-based regimens have been associated with renal function worsening in HCV patients with estimated glomerular filtration rate (eGFR) ≤ 45 ml/min, but further investigations are lacking. AIM To assess renal safety in a large cohort of DAA-treated HCV patients with any chronic kidney disease (CKD). METHODS All HCV patients treated with DAA in Lombardy (December 2014-November 2017) with available kidney function tests during and off-treatment were included. RESULTS Among 3264 patients [65% males, 67% cirrhotics, eGFR 88 (9-264) ml/min], CKD stage was 3 in 9.5% and 4/5 in 0.7%. 79% and 73% patients received SOF and RBV, respectively. During DAA, eGFR declined in CKD-1 (p < 0.0001) and CKD-2 (p = 0.0002) patients, with corresponding rates of CKD stage reduction of 25% and 8%. Conversely, eGFR improved in lower CKD stages (p < 0.0001 in CKD-3a, p = 0.0007 in CKD-3b, p = 0.024 in CKD-4/5), with 33-45% rates of CKD improvement. Changes in eGFR and CKD distribution persisted at SVR. Baseline independent predictors of CKD worsening at EOT and SVR were age (p < 0.0001), higher baseline CKD stages (p < 0.0001) and AH (p = 0.010 and p < 0.0001, respectively). CONCLUSIONS During DAA, eGFR significantly declined in patients with preserved renal function and improved in those with lower CKD stages, without reverting upon drug discontinuation.
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Iliescu EL, Mercan-Stanciu A, Toma L. Safety and efficacy of direct-acting antivirals for chronic hepatitis C in patients with chronic kidney disease. BMC Nephrol 2020; 21:21. [PMID: 31948406 PMCID: PMC6966843 DOI: 10.1186/s12882-020-1687-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 01/07/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND This is a real-world evidence study that aims to analyze the efficacy, tolerability and safety profile of paritaprevir/ombitasvir/ritonavir and dasabuvir, in patients with renal impairment. METHODS We conducted an observational prospective study, on 232 patients with chronic kidney disease, undergoing treatment with paritaprevir/ombitasvir/ritonavir and dasabuvir, for chronic hepatitis C infection - genotype 1b. Renal and liver function were assessed at the beginning of therapy, monthly during treatment and three months after therapy completion. RESULTS All patients achieved sustained virologic response. Common side effects were nausea, fatigue and headache. Close monitoring of tacrolimus blood levels and dose reduction was required in kidney transplant recipients. CONCLUSIONS HCV therapy in the setting of renal dysfunction has always been a challenging topic. Direct-acting antivirals have shown promising effects, demonstrating good tolerance and efficacy in patients with HCV infection and renal impairment. Sustained virologic response within our study population was 100%.
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Affiliation(s)
- Elena Laura Iliescu
- Department of Internal Medicine II, Fundeni Clinical Institute, 022328, Bucharest, Romania.
| | - Adriana Mercan-Stanciu
- Department of Internal Medicine II, Fundeni Clinical Institute, 022328, Bucharest, Romania
| | - Letitia Toma
- Department of Internal Medicine II, Fundeni Clinical Institute, 022328, Bucharest, Romania
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Yaraş S, Üçbilek E, Özdoğan O, Ateş F, Altıntaş E, Sezgin O. Real-life results of treatment with ombitasvir, paritaprevir, dasabuvir, and ritonavir combination in patients with chronic renal failure infected with HCV in Turkey. TURKISH JOURNAL OF GASTROENTEROLOGY 2019; 30:331-335. [PMID: 30666967 DOI: 10.5152/tjg.2018.18269] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND/AIMS As the most common liver disease in hemodialysis patients, chronic hepatitis C (CHC) can cause cirrhosis and hepatocellular carcinoma, even increase in renal-related mortality. In Turkey, the frequency of anti-hepatitis C virus (HCV) antibodies in hemodialysis patients ranged from 31.4% to 51%. Until recently, the mainstay of the CHC treatment for these patients was pegylated interferon with potential toxicities and low sustained virological response. The 3D regimen, a combination of four drugs (ombitasvir, paritaprevir, dasabuvir, and ritonavir), has recently been used for patients with chronic kidney disease infected with genotype 1a and 1b HCV. The aim of the present study was to present results of 3D treatment for patients with hemodialysis-dependent chronic renal failure (CRF) who were chronically infected with HCV. MATERIALS AND METHODS Overall, 25 patients with hemodialysis-dependent CRF who were infected with genotype 1a/1b HCV have been treated using the 3D regimen in our gastroenterology clinic between July 2016 and October 2017. Three patients were administered additional ribavirin 200 mg/day. Serum HCV RNAs, blood chemistry, blood count, and side effects were recorded at 0, 4, and 12 weeks. RESULTS All 25 patients completed and well tolerated their planned treatment. At the end of 4 weeks, the viral response (defined as HCV RNA clearance) rate was 92%. At the end of 12 weeks of treatment and 3 months after treatment, viral response rates were both 100%. CONCLUSION We observed that the treatment with 3D regimen in hemodialysis patients infected with genotype 1 hepatitis C is highly effective and well tolerated.
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Affiliation(s)
- Serkan Yaraş
- Department of Gastroenterology, Mersin University School of Medicine, Mersin, Turkey
| | - Enver Üçbilek
- Department of Gastroenterology, Mersin University School of Medicine, Mersin, Turkey
| | - Osman Özdoğan
- Department of Gastroenterology, Mersin University School of Medicine, Mersin, Turkey
| | - Fehmi Ateş
- Department of Gastroenterology, Mersin University School of Medicine, Mersin, Turkey
| | - Engin Altıntaş
- Department of Gastroenterology, Mersin University School of Medicine, Mersin, Turkey
| | - Orhan Sezgin
- Department of Gastroenterology, Mersin University School of Medicine, Mersin, Turkey
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Ali S, Ali M, Paudyal V, Rasheed F, Ullah S, Haque S, Ur-Rehman T. A Randomized Controlled Trial to Assess the Impact of Clinical Pharmacy Interventions on Treatment Outcomes, Health Related Quality of Life and Medication Adherence Among Hepatitis C Patients. Patient Prefer Adherence 2019; 13:2089-2100. [PMID: 31997877 PMCID: PMC6917610 DOI: 10.2147/ppa.s224937] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2019] [Accepted: 10/30/2019] [Indexed: 12/15/2022] Open
Abstract
PURPOSE The role of specialized pharmacy services remains unexplored in clinical practice for hepatitis C patients in Pakistan. This study aimed to evaluate the impact of clinical pharmacy interventions on treatment outcomes, health-related quality of life (HRQoL), and medication adherence among hepatitis C patients. METHODS A randomized control trial was conducted at two tertiary-care teaching hospitals in Pakistan. Hepatitis C patients who attended the outpatient clinics between October 2015 and September 2018 were randomized to two groups [usual care (UC) and pharmaceutical care (PC)] in a 1:1 ratio, applying simple envelope method. The PC group received pharmaceutical care led by a clinical pharmacist. The care that patients received included education and counseling on medication compliance, labeling of medication packs, and monitoring of adverse drug events, led by a qualified clinical pharmacist during the 15- to 20-minute monthly sessions, while the UC group received standard care at hospital, which did not involve clinical pharmacist input. Outcome measures, such as sustained virological response, HRQoL, and adherence rate (pharmacy data) were assessed at enrolment and distinct time intervals: 4 weeks, 8 weeks, and end of treatment. RESULTS A total of 931 patients were included in the study (UC 466 and PC 465), with mean age 42.35±1.9 years. Sustained virological response at 12 weeks was achieved in 86.0% patients in the PC group, significantly (p<0.001) higher than the UC (69.3%) group. Fewer patients (9.9%) in the PC group reported mobility problems, significantly fewer (p<0.001) than the UC group (11.8%). Self-care, usual activity, pain, and depression were relieved significantly in the PC group compared to the UC group. The EuroQol visual analogue scale (baseline 56.1 of UC group versus 55.2 for PC group) was raised to 71.8 and 71.9 in the UC and PC groups, respectively. Medication adherence was significantly improved (p<0.001) in the PC group (88.6%) when compared to the UC group (77.9%, 95% CI 88.9%-91.9%). CONCLUSION Pharmacist-led clinical pharmacy interventions as part of multidisciplinary care had a significant impact on improving cure rates, HRQoL, and medication adherence for hepatitis C patients. This study suggests that clinical pharmacists should be incorporated into the multidisciplinary health-care team for care of hepatitis C patients.
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Affiliation(s)
- Salamat Ali
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan
- Services Institute of Medical Sciences, Lahore, Pakistan
| | - Mashhood Ali
- Department of Gastroenterology, Pakistan Institute of Medical Sciences, Islamabad, Pakistan
| | - Vibhu Paudyal
- School of Pharmacy, University of Birmingham, Birmingham, UK
| | - Faisal Rasheed
- Pakistan Institute of Nuclear Sciences and Technology, Islamabad, Pakistan
| | - Shahan Ullah
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan
| | - Sayeed Haque
- Institute of Applied Health Research Medical Statistics, University of Birmingham, Birmingham, UK
| | - Tofeeq Ur-Rehman
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan
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First Molecular Evidences of Acanthamoeba T3, T4 and T5 Genotypes in Hemodialysis Units in Iran. Acta Parasitol 2019; 64:911-915. [PMID: 31552581 DOI: 10.2478/s11686-019-00122-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 09/09/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Acanthamoeba is a genus of the free-living amoeba that is widespread in the environment and is a causative agent of opportunistic infections in human. This study aimed to investigate the existence and genotyping of Acanthamoeba species in hemodialysis units in Iran. METHODS In the present study, forty water samples of hydraulic systems and twenty dust samples were collected from two hemodialysis units in Mazandaran Province, northern Iran. The samples were cultivated on non-nutrient agar and genotyping was performed by targeting the 18S rRNA gene. RESULTS Both morphology and molecular analyses showed that 17.5% (7/40) of water samples and 50% (10/20) of dust samples were positive for Acanthamoeba spp. The sequencing analysis of these isolates was found to be T3, T4 and T5 genotypes. DISCUSSION To the best of our knowledge, this is the first investigation to identify of Acanthamoeba species in hydraulic system of hemodialysis units in Iran. High contamination of hemodialysis units with virulent T4 genotype of Acanthamoeba may poses a risk for biofilm formation. Our results support urgent need to improve filtration methods in dialysis units and monitoring hemodialysis patients for Acanthamoeba infections.
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Tsai MC, Lin CY, Hung CH, Lu SN, Tung SY, Chien RN, Lin CL, Wang JH, Chien-Hung C, Chang KC, Hu TH, Sheen IS. Evolution of renal function under direct-acting antivirals treatment for chronic hepatitis C: A real-world experience. J Viral Hepat 2019; 26:1404-1412. [PMID: 31433885 DOI: 10.1111/jvh.13193] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Accepted: 07/19/2019] [Indexed: 01/22/2023]
Abstract
Renal toxicity of direct-acting antivirals (DAAs) in chronic hepatitis C (CHC) patients has not been well-characterized. The aim of this study was to assess renal safety of DAAs in an Asian CHC patient cohort. Data from CHC patients (n = 1536) treated with DAAs were used in this retrospective study. Serial estimated glomerular filtration rate (eGFR) at pretreatment (1-year prior to treatment), baseline, end of treatment (EOT), and 12 weeks after treatment (SVR12 ) was evaluated. While a significant decrease in eGFR from baseline to EOT (84.8 → 81.8 mL/min/1.73 m2 , P < .001) was observed; subsequently, a slight rise at SVR12 (84.3 mL/min/1.73 m2 ) was also evident. Changes in eGFR after DAA treatment were similar to those seen in PrOD, DCV/ASV and GZP/EBV regimens, except in the SOF-based regimen wherein eGFR remained unchanged from EOT to SVR12 , especially in liver transplant recipients. Multivariate analysis revealed that age >65 years (OR = 1.862, P = .011), baseline eGFR ≥ 60 mL/min/1.73 m2 (OR = 2.684, P = .023), and liver transplant (OR = 3.894, P = .001) were independent risk factors for deteriorating renal function. In conclusion, DAA treatment led to a significant decline in eGFR at EOT but was followed by a slight rise at 12 weeks after treatment. A similar trend was observed with PrOD, DCV/ASV and GZP/EBV, but not in SOF-based regimens. As age >65 years, baseline eGFR ≥ 60 mL/min/1.73 m2 and liver transplantation are significant risk factors for deterioration in renal function, we strongly advice close monitoring of renal function in these populations.
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Affiliation(s)
- Ming-Chao Tsai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.,Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taiwan
| | - Chun-Yen Lin
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.,Division of Hepato-Gastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Sheng-Nan Lu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.,Division of Hepato-Gastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Shui-Yi Tung
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Rong-Nan Chien
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Chih-Lang Lin
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Jing-Houng Wang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chen Chien-Hung
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kuo-Chin Chang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - I-Shyan Sheen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
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Liu CH, Shih YL, Yang SS, Lin CL, Fang YJ, Cheng PN, Chen CY, Peng CY, Hsieh TY, Chiu YC, Su TH, Liu CJ, Yang HC, Chen PJ, Chen DS, Kao JH. Paritaprevir/ritonavir, ombitasvir plus dasabuvir for East Asian non-cirrhotic hepatitis C virus genotype 1b patients receiving hemodialysis. J Gastroenterol Hepatol 2019; 34:1977-1983. [PMID: 30931537 DOI: 10.1111/jgh.14672] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 03/04/2019] [Accepted: 03/21/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Data regarding the efficacy and safety of paritaprevir/ritonavir, ombitasvir plus dasabuvir (PrOD) for East Asian non-cirrhotic hepatitis C virus genotype 1b (HCV GT1b) patients receiving hemodialysis were limited. METHODS Forty-six HCV GT1b non-cirrhotic patients receiving hemodialysis who received PrOD for 12 weeks were prospectively enrolled in seven academic centers in Taiwan. The primary efficacy endpoint was sustained virologic response 12 weeks off-therapy (SVR12 ). Patients' baseline characteristics, early virokinetics, and HCV resistance-associated substitutions (RASs) potentially related to SVR12 were analyzed. The safety profiles were also assessed. RESULTS The SVR12 rate was 100% (46 of 46 patients). Patients' baseline characteristics, on-treatment viral decline, and baseline HCV resistance-associated substitutions did not affect SVR12 . All patients tolerated treatment well. One patient with folliculitis temporarily discontinued treatment, and another two patients had serious adverse events (SAEs), which were considered not related to PrOD treatment. The common adverse events were pruritus (19.6%), fatigue (15.2%), and upper respiratory tract infection (6.5%). Twelve (19.6%) and one (2.2%) patients had hemoglobin levels < 10 and 8.5 g/dL, respectively, which were related to renal impairment. Five (10.9%) patients had on-treatment total bilirubin level of 1.5-3.0 mg/dL, but none developed hepatic decompensation. The bilirubin levels peaked at week 1 of treatment and then declined with continuous treatment. CONCLUSION Treatment with PrOD for 12 weeks is efficacious and well-tolerated for East Asian non-cirrhotic HCV GT1b patients receiving hemodialysis.
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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, Douliou, Taiwan
| | - Yu-Lueng Shih
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Sheng-Shun Yang
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan.,School of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chih-Lin Lin
- Department of Gastroenterology, Taipei City Hospital, Renai Branch, Taipei, Taiwan
| | - Yu-Jen Fang
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Douliou, Taiwan
| | - Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Chi-Yi Chen
- Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan
| | - Cheng-Yuan Peng
- Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Yen-Cheng Chiu
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Tung-Hung Su
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Pei-Jer Chen
- 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
| | - Ding-Shinn Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Genomics Research Center, Academia Sinica, 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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Hepatitis C therapy with direct antiviral agents in patients with advanced chronic kidney disease: real-world experience of the German Hepatitis C-Registry (Deutsches Hepatitis C-Register). Eur J Gastroenterol Hepatol 2019; 31:1424-1431. [PMID: 31589184 DOI: 10.1097/meg.0000000000001426] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Direct-acting antiviral agents (DAAs) have revolutionized treatment of chronic hepatitis C in patients with normal glomerular filtration rate (GFR). However, patients with impaired kidney function have been excluded from several clinical trials. We, therefore, investigated the use, effectiveness, and tolerability of DAAs in patients with GFR less than 30 ml/min in the real-world setting. PATIENTS AND METHODS An analysis was done within the German Hepatitis C-Registry on 5733 patients including 46 individuals with a baseline GFR less than 30 ml/min treated with sofosbuvir-based (61%) or paritaprevir/ritonavir-based (39%) regimens. RESULTS Sustained virological response 12 rates did not differ significantly between patients with baseline GFR less than 30 versus more than 30 ml/min (91 vs. 96%). Nine individuals with a baseline GFR more than 30 ml/min presented with a GFR less than 30 ml/min at the end of treatment. GFR improvement from less than 30 ml/min to more than 30 ml/min was observed in 9/46 cases. Adverse events did not differ in patients with GFR less than 30 versus more than 30 ml/min. However, serious adverse events were significantly more frequent in individuals with GFR less than 30 ml/min and associated with ribavirin. CONCLUSION Different DAA therapies can be safely used with high sustained virological response rates in patients with GFR less than 30 ml/min. Ribavirin has to be avoided because of poor tolerability.
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Londoño MC, Riveiro-Barciela M, Ahumada A, Muñoz-Gómez R, Roget M, Devesa-Medina MJ, Serra MÁ, Navascués CA, Baliellas C, Aldamiz-Echevarría T, Gutiérrez ML, Polo-Lorduy B, Carmona I, Benlloch S, Bonet L, García-Samaniego J, Jiménez-Pérez M, Morán-Sánchez S, Castro Á, Delgado M, Gea-Rodríguez F, Martín-Granizo I, Montes ML, Morano L, Castaño MA, de los Santos I, Laguno M, Losa JE, Montero-Alonso M, Rivero A, de Álvaro C, Manzanares A, Mallolas J, Barril G, González-Parra E, García-Buey L. Effectiveness, safety/tolerability of OBV/PTV/r ± DSV in patients with HCV genotype 1 or 4 with/without HIV-1 co-infection, chronic kidney disease (CKD) stage IIIb-V and dialysis in Spanish clinical practice - Vie-KinD study. PLoS One 2019; 14:e0221567. [PMID: 31550267 PMCID: PMC6759177 DOI: 10.1371/journal.pone.0221567] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Accepted: 08/11/2019] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND AND AIMS Limited data are available on the effectiveness and tolerability of direct-acting antivirals (DAAs) therapies in the real world for HCV-infected patients with comorbidities. This study aimed to describe the effectiveness of OBV/PTV/r ± DSV (3D/2D regimen) with or without ribavirin (RBV) in HCV or HCV/HIV co-infected patients with GT1/GT4 and CKD (IIIb-V stages), including those under hemodialysis and peritoneal dialysis in routine clinical practice in Spain in 2015. MATERIAL AND METHODS Non-interventional, retrospective, multicenter data collection study in 31 Spanish sites. Socio-demographic, clinical variables, study treatment characteristics, effectiveness and tolerability data were collected from medical records. RESULTS Data from 135 patients with a mean age (SD) of 58.3 (11.4) years were analyzed: 92.6% GT1 (81.6% GT1b and 17.6% GT1a) and 7.4% GT4, 14 (10.4%) HIV/HCV co-infected, 19.0% with fibrosis F3 and 28.1% F4 by FibroScan®, 52.6% were previously treated with pegIFN and RBV. 11.1%, 14.8% and 74.1% of patients had CKD stage IIIb, IV and V respectively. 68.9% of patients were on hemodialysis; 8.9% on peritoneal dialysis and 38.5% had history of renal transplant. A total of 125 (96.2%) of 135 patients were treated with 3D, 10 (7.4%) with 2D and 30.4% received RBV. The overall intention-to-treat (ITT) sustained virologic response at week 12 (SVR12) was 92.6% (125/135) and the overall modified-ITT (mITT) SVR12 was 99.2% (125/126). The SVR12 rates (ITT) per sub-groups were: HCV mono-infected (91.7%), HCV/HIV co-infected (100%), GT1 (92.0%), GT4 (100%), CKD stage IIIb (86.7%), stage IV (95%) and stage V (93%). Among the 10 non-SVR there was only 1 virologic failure (0.7%); 4 patients had missing data due lost to follow up (3.0%) and 5 patients discontinued 3D/2D regimen (3.7%): 4 due to severe adverse events (including 3 deaths) and 1 patient´s decision. CONCLUSIONS These results have shown that 3D/2D regimens are effective and tolerable in patients with advanced CKD including those in dialysis with GT 1 or 4 chronic HCV mono-infection and HIV/HCV coinfection in a real-life cohort. The overall SVR12 rates were 92.6% (ITT) and 99.2% (mITT) without clinically relevant changes in eGFR until 12 weeks post-treatment. These results are consistent with those reported in clinical trials.
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Affiliation(s)
- María-Carlota Londoño
- Liver Unit, Hospital Clínic/IDIBAPS, Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERhed), Instituto de Salud Carlos III, Madrid, Madrid, Spain
| | - Mar Riveiro-Barciela
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERhed), Instituto de Salud Carlos III, Madrid, Madrid, Spain
- Liver Unit, Internal Medicine Department, Hospital Vall d'Hebron, Barcelona, Barcelona, Spain
| | - Adriana Ahumada
- Department of Gastroenterology, Hospital General Universitario Gregorio Marañón, Madrid, Madrid, Spain
| | - Raquel Muñoz-Gómez
- Department of Gastroenterology, Hospital General Universitario 12 de Octubre, Madrid, Madrid, Spain
| | - Mercé Roget
- Liver Unit, Consorci Sanitari de Terrassa, Terrassa, Barcelona, Spain
| | - María J. Devesa-Medina
- Department of Gastroenterology, Hospital Universitario Clínico San Carlos, Madrid, Madrid, Spain
| | - Miguel Ángel Serra
- Digestive Medicine Service, Hospital Clínico Universitario de Valencia, Universidad de Valencia, Valencia, Spain
| | - Carmen A. Navascués
- Department of Gastroenterology, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain
| | - Carme Baliellas
- Liver Unit, Hospital de Bellvitge, Institut d'Investigació Biomèdica de Bellvitge, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Teresa Aldamiz-Echevarría
- Infectious Diseases-HIV Hospital General Universitario Gregorio Marañón (IiSGM), Madrid, Madrid, Spain
| | - María L. Gutiérrez
- Department of Gastroenterology, Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain
| | - Benjamín Polo-Lorduy
- Digestive Diseases Unit, Hospital Universitario Fundación Jiménez Díaz, Madrid, Madrid, Spain
| | - Isabel Carmona
- Digestive Disease Unit, Hospital Universitario Virgen Macarena, Sevilla, Sevilla, Spain
| | - Salvador Benlloch
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERhed), Instituto de Salud Carlos III, Madrid, Madrid, Spain
- Department of Hepatology, Hospital Universitario y Politécnico La Fe, Valencia, Valencia, Spain
| | - Lucía Bonet
- Department of Gastroenterology, Hospital Universitario Son Espases, Palma de Mallorca, Mallorca, Spain
| | - Javier García-Samaniego
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERhed), Instituto de Salud Carlos III, Madrid, Madrid, Spain
- Liver Unit, Hospital Universitario La Paz/IdiPaz, Madrid, Madrid, Spain
| | | | | | - Ángeles Castro
- Complejo Hospitalario Universitario A Coruña, A Coruña, Spain
| | - Manuel Delgado
- Complejo Hospitalario Universitario A Coruña, A Coruña, Spain
| | - Francisco Gea-Rodríguez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERhed), Instituto de Salud Carlos III, Madrid, Madrid, Spain
- Department of Gastroenterology, Hospital Universitario Ramón y Cajal, Madrid, Madrid, Spain
| | - Ignacio Martín-Granizo
- Department of Gastroenterology, Hospital Universitario Álvaro Cunqueiro, Vigo, Pontevedra, Spain
| | | | - Luís Morano
- Infectious Disease Unit, Internal Medicine Department, Hospital Universitario Álvaro Cunqueiro, Vigo, Pontevedra, Spain
| | | | - Ignacio de los Santos
- Department of Internal Medicine, Hospital Universitario La Princesa, Madrid, Madrid, Spain
| | - Montserrat Laguno
- HIV Unit, Infectious Diseases Service, Hospital Clínic/IDIBAPS, Barcelona, Barcelona, Spain
| | - Juan Emilio Losa
- Infectious Diseases Unit, Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain
| | - Marta Montero-Alonso
- Infectious Diseases Unit, Hospital Universitario y Politécnico La Fe, Valencia, Valencia, Spain
| | - Antonio Rivero
- Infectious Diseases Unit, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, Córdoba, Spain
| | | | - Amanda Manzanares
- Medical Department & Quality Assurance, ABBVIE, Madrid, Madrid, Spain
| | - Josep Mallolas
- HIV Unit, Infectious Diseases Service, Hospital Clínic/IDIBAPS, Barcelona, Barcelona, Spain
| | - Guillermina Barril
- Nephrology Unit, Hospital Universitario La Princesa, Madrid, Madrid, Spain
| | - Emilio González-Parra
- Nephrology Unit, Hospital Universitario Fundación Jiménez Díaz, Madrid, Madrid, Spain
| | - Luisa García-Buey
- Liver Unit, Hospital Universitario La Princesa, Madrid, Madrid, Spain
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Elmowafy AY, El Maghrabi HM, Eldahshan KF, Refaie AF, Elbasiony MA, Matter YE, Saleh HH, Shiha GE, Rostaing L, Bakr MA. Treatment of hepatitis C infection among Egyptian hemodialysis patients: the dream becomes a reality. Int Urol Nephrol 2019; 51:1639-1647. [PMID: 31363959 DOI: 10.1007/s11255-019-02246-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2019] [Accepted: 07/21/2019] [Indexed: 01/07/2023]
Abstract
BACKGROUND AND AIMS New direct-acting antiviral drugs have become the corner-stone treatment for HCV infection: they show promising results with accepted side-effects and low dropout rates. One of the available regimens is paritaprevir/ombitasvir/ritonavir (PTV/OMV/RTV). Our aim was to study the efficacy and safety of this drug regimen among HCV-positive hemodialysis patients. METHODS This prospective single-center study was performed in the Urology and Nephrology Center, Mansoura University, Egypt. Ninety-six maintenance hemodialysis patients were screened for HCV antibodies. Positive results were found in 46 patients (47.9%). HCV PCR was assessed in all HCV-antibody-positive patients; positive results were found positive for 38 (82%); all patients were HCV genotype 4. Four patients were excluded due to advanced liver cirrhosis, liver malignancy, or metastatic breast cancer. Thirty-four patients were prescribed PTV/OMV/RTV for 3 months to treat HCV. RESULTS Mean age was 43.2 ± 11.9 years. Most patients were male (67.6%). There was a rapid response to treatment: HCV PCR became negative by 4 weeks after starting treatment. By 12 and 24 weeks post-DAA therapy, there was a sustained viral response (SVR 12, SVR 24) in 100% of patients with improved liver-enzyme levels. CONCLUSION The PTV/OMV/RTV regimen was safe and effectively treated Egyptian HCV-positive genotype-4 hemodialysis patients.
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Affiliation(s)
| | - Hanzada Mohamed El Maghrabi
- Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.,Nephrology Department, Port-Said University, Port Fuad, Egypt
| | | | | | - Mohammed Adel Elbasiony
- Egyptian Liver Research Institute and Hospital, Mansoura, Egypt.,Internal Medicine Department, Mansoura University, Mansoura, Egypt
| | | | | | | | - Lionel Rostaing
- Service de Néphrologie, Dialyse, Aphérèses et Transplantation Rénale, CHU Grenoble Alpes, CS 10217, 38043, Grenoble Cedex 09, France.
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Efficacy and safety of glecaprevir/pibrentasvir for chronic hepatitis C virus genotypes 1-6 infection: A systematic review and meta-analysis. Int J Antimicrob Agents 2019; 54:780-789. [PMID: 31284039 DOI: 10.1016/j.ijantimicag.2019.07.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Revised: 04/16/2019] [Accepted: 07/03/2019] [Indexed: 02/08/2023]
Abstract
This systematic review and meta-analysis investigated the efficacy and safety of glecaprevir and pibrentasvir (G/P) for chronic hepatitis C virus (HCV) infection. Pubmed, Embase, Cochrane Library and Scopus were searched to identify relevant studies through August 2018. Data from eligible studies were pooled and sustained virological response rates at 12 weeks' post-treatment (SVR12) were calculated. Thirteen studies with 3082 patients were included and the overall SVR12 rate was 97.8%. The SVR12 rates of subgroups were: G/P 300 mg/120 mg and 200 mg/120 mg: 97.9% and 98.3%; HCV genotype (GT)1, GT2, GT3 and GT4-6: 99.8%, 99.2%, 96.1% and 100%; G/P and G/P plus ribavirin (RBV): 97.9% and 98.2%; G/P (300 mg/120 mg) for 8 weeks, 12 weeks and 16 weeks: 98.8%, 98.5% and 95.6%; treatment-naïve and treatment-experienced patients: 96.7% and 98.3%; patients without and with compensated cirrhosis: 99.4% and 98.8%; patients without and with human immunodeficiency virus (HIV) co-infection: 97.8% and 99.4%; and patients without and with severe renal impairment (SRI): 97.8% and 99.4%. Virological failure and relapse and serious drug-related adverse events were rare. These results indicate that 8- or 12-week G/P treatment achieved high SVR12 rates in HCV GTs 1-6 patients without or with compensated cirrhosis, with good safety profiles, irrespective of dose, RBV use, treatment-experience, HIV co-infection and renal impairment. Due to the limited number of evaluated patients with GT3 infection, further studies are needed to define optimal treatment duration for GT3 cirrhosis patients and patients with prior treatment experience of direct-acting antivirals.
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