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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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Prabhu AR, Rao IR, Nagaraju SP, Rajwar E, Venkatesh BT, Nair N S, Pai G, Reddy NP, Suvarna D. Interventions for dialysis patients with hepatitis C virus (HCV) infection. Cochrane Database Syst Rev 2023; 4:CD007003. [PMID: 37096802 PMCID: PMC10130818 DOI: 10.1002/14651858.cd007003.pub3] [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] [Indexed: 04/26/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is common in chronic kidney disease (CKD) patients on dialysis, causes chronic liver disease, may increase the risk of death, and impacts kidney transplant outcomes. Direct-acting antivirals have replaced interferons because of better efficacy and tolerability. This is an update of a review first published in 2015. OBJECTIVES We aimed to look at the benefits and harms of interventions for HCV in CKD patients on dialysis: death, disease relapse, treatment response/discontinuation, time to recovery, quality of life (QoL), cost-effectiveness, and adverse events. We aimed to study comparisons of available interventions, compared with placebo, control, with each other and with newer treatments. SEARCH METHODS We searched the Cochrane Kidney and Transplant's Specialised Register to 23 February 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE and EMBASE, handsearching conference proceedings, and searching the International Clinical Trials Register Portal (ICTRP) and ClinicalTrials.gov. SELECTION CRITERIA Randomised controlled trials (RCTs), quasi-RCTs, first period of randomised cross-over studies on interventions for HCV in CKD on dialysis were considered. DATA COLLECTION AND ANALYSIS Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS Three studies were included in this update, therefore 13 studies (997 randomised participants) met our inclusion criteria. Overall, the risk of bias was judged low in seven studies, unclear in four, low to unclear in one, and high in one study. Interventions included standard interferon, pegylated (PEG) interferon, standard or PEG interferon plus ribavirin; direct-acting antivirals, and direct-acting antivirals plus PEG interferon plus ribavirin. Compared to placebo or control, standard interferon may make little or no difference to death (5 studies, 134 participants: RR 0.89, 95% CI 0.06 to 13.23) or relapse (low certainty evidence), probably improves end-of-treatment response (ETR) (5 studies, 132 participants: RR 8.62, 95% CI 3.03 to 24.55; I² = 0%) (moderate certainty evidence), and probably makes little or no difference to sustained virological response (SVR) (4 studies, 98 participants: RR 3.25, 95% CI 0.81 to 13.07; I² = 53%), treatment discontinuation (4 studies, 116 participants: RR 4.59, 95% CI 0.49 to 42.69; I² = 63%), and adverse events (5 studies, 143 participants: RR 3.56, 95% CI 0.98 to 13.01; I² = 25%) (moderate certainty evidence). In low certainty evidence, PEG interferon (1 study, 50 participants) may improve ETR (RR 1.53, 95% CI 1.09 to 2.15) but may make little or no difference to death (RR 0.33, 95% CI 0.01 to 7.81), SVR (RR 2.40, 95% CI 0.99 to 5.81), treatment discontinuation (RR 0.11, 95% CI 0.01 to 1.96), adverse events (RR 0.11, 95% CI 0.01 to 1.96) and relapses (21/38 relapsed) (RR 0.72, 95% CI 0.41 to 1.25) compared to standard interferon. In moderate certainty evidence, high-dose PEG interferon (alpha-2a and alpha-2b) may make little or no difference to death (2 studies, 97 participants: RR 4.30, 95% CI 0.76 to 24.33; I² = 0%), ETR (RR 1.42, 95% CI 0.51 to 3.90; I² = 20%), SVR (RR 1.19, 95% CI 0.68 to 2.07; I² = 0%), treatment discontinuation (RR 1.20, 95% CI 0.63 to 2.28; I² = 0%) or adverse events (RR 1.05, 95% CI 0.61 to 1.83; I² = 27%) compared to low-dose PEG interferon. High-dose PEG interferon may make little or no difference to relapses (1 study, 43 participants: RR 1.11, 95% CI 0.45 to 2.77; low certainty evidence). There were no significant subgroup differences. Standard interferon plus ribavirin may lead to higher treatment discontinuation (1 study, 52 participants: RR 2.97, 95% CI 1.19 to 7.36; low certainty evidence) compared to standard interferon alone. In low certainty evidence, PEG interferon plus ribavirin (1 study, 377 participants) may improve SVR (RR 1.80, 95% CI 1.46 to 2.21), reduce relapses (RR 0.33, 95% CI 0.23 to 0.48), slightly increase the number with adverse events (RR 1.10, 95% CI 1.01 to 1.19), and may make little or no difference to ETR (RR 1.01, 95% CI 0.94 to 1.09) compared to PEG interferon alone. The evidence is very uncertain about the effect of PEG interferon plus ribavirin on treatment discontinuation (RR 1.71, 95% CI 0.69 to 4.24) compared to PEG interferon alone. One study reported grazoprevir plus elbasvir improved ETR (173 participants: RR 174.99, 95% CI 11.03 to 2775.78; low certainty evidence) compared to placebo. It is uncertain whether telaprevir plus ribavirin (high versus low initial dose) plus PEG interferon for 24 versus 48 weeks (1 study, 35 participants) improves ETR (RR 1.02, 95% CI 0.67 to 1.56) or SVR (RR 1.02, 95% CI 0.67 to 1.56) because the certainty of the evidence is very low. Data on QoL, cost-effectiveness, cardiovascular outcomes and peritoneal dialysis were not available. AUTHORS' CONCLUSIONS In dialysis patients with HCV infection grazoprevir plus elbasvir probably improves ETR. There is no difference in ETR or SVR for combinations of telaprevir, ribavirin and PEG interferon given for different durations and doses. Though no longer in use, PEG interferon was more effective than standard interferon for ETR but not SVR. Increasing doses of PEG interferon did not improve responses. The addition of ribavirin to PEG interferon may result in fewer relapses, higher SVR, and higher numbers with adverse events.
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Affiliation(s)
- Attur Ravindra Prabhu
- Department of Nephrology, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, India
| | - Indu Ramachandra Rao
- Department of Nephrology, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, India
| | - Shankar Prasad Nagaraju
- Department of Nephrology, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, India
| | - Eti Rajwar
- Public Health Evidence South Asia (PHESA), Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, India
| | - Bhumika T Venkatesh
- Public Health Evidence South Asia (PHESA), Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, India
| | - Sreekumaran Nair N
- Department of Medical Biometrics & Informatics (Biostatistics), Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) (Institution of National Importance Under Ministry of Health and Family Welfare, Government of India), Dhanvantri Nagar, India
| | - Ganesh Pai
- Department of Gastroenterology, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, India
| | | | - Deepak Suvarna
- Department of Gastroenterology, JSS Medical College, Mysore, India
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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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Liu CH, Kao JH. Pan-genotypic direct-acting antivirals for patients with hepatitis C virus infection and chronic kidney disease stage 4 or 5. Hepatol Int 2022; 16:1001-1019. [PMID: 35876967 PMCID: PMC9309604 DOI: 10.1007/s12072-022-10390-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 07/03/2022] [Indexed: 12/17/2022]
Abstract
Hepatitis C virus (HCV) infection is a major health problem with significant clinical and economic burdens in patients with chronic kidney disease (CKD) stage 4 or 5. Current guidelines recommend pan-genotypic direct-acting antivirals (DAAs) to be the first-line treatment of choice for HCV. This review summarizes the updated knowledge regarding the epidemiology, natural history, public health perspectives of HCV in patients with CKD stage 4 or 5, including those on maintenance dialysis, and the performance of pan-genotypic DAAs in these patients. The prevalence and incidence of HCV are much higher in patients with CKD stage 4 or 5 than in the general population. The prognosis is compromised if HCV patients are left untreated regardless of kidney transplantation (KT). Following treatment-induced HCV eradication, patient can improve the health-related outcomes by maintaining a long-term aviremic state. The sustained virologic response (SVR12) rates and safety profiles of pan-genotypic DAAs against HCV are excellent irrespective of KT. No dose adjustment of pan-genotypic DAAs is required across CKD stages. Assessing drug-drug interactions (DDIs) before HCV treatment is vital to secure on-treatment safety. The use of prophylactic or preemptive pan-genotypic DAAs in HCV-negative recipients who receive HCV-positive kidneys has shown promise in shortening KT waiting time, achieving excellent on-treatment efficacy and safety, and maintaining post-KT patient and graft survival. HCV elimination is highly feasible through multifaceted interventions, including mass screening, treatment scale-up, universal precautions, and post-SVR12 reinfection surveillance.
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Affiliation(s)
- Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and Hospital, 7 Chung-Shan South Road, Taipei, 10002 Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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Liu CH, Peng CY, Kao WY, Yang SS, Shih YL, Lin CL, Tsai MK, Lee CY, Chang CC, Wu JH, Liu CJ, Su TH, Tseng TC, Chen PJ, Kao JH. Hepatitis C virus reinfection in patients on haemodialysis after achieving sustained virologic response with antiviral treatment. Aliment Pharmacol Ther 2022; 55:434-445. [PMID: 34773272 DOI: 10.1111/apt.16697] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 10/12/2021] [Accepted: 10/29/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Data are limited regarding the risk of hepatitis C virus (HCV) reinfection after treatment-induced sustained virologic response (SVR) in patients on haemodialysis. AIMS To assess the risk of HCV reinfection among patients on haemodialysis with treatment-induced SVR. METHODS Patients on haemodialysis patients who achieved SVR12 with interferon (IFN) or direct-acting antiviral (DAA)-based treatment received follow-up at SVR24 and then biannually with HCV RNA measurements. HCV reinfection was defined as the resurgence of viremia by different viral strains beyond SVR12 . The low-risk general population who achieved SVR12 and who underwent the same post-SVR12 surveillance served as the reference group. Crude reinfection rates per 100 person-years (PYs) were calculated. Multivariate Cox regression analysis was performed to estimate the relative risk of HCV reinfection between the two groups. RESULTS We recruited 374 patients on haemodialysis and 1571 reference patients with a mean post-SVR12 follow-up of 4.7 and 6.1 years. All haemodialysis patients who achieved SVR12 also achieved SVR24 . The incidence rates of HCV reinfection were 0.23 per 100 PYs (95% confidence interval [CI]: 0.09-0.59) in haemodialysis patients and 0.16 per 100 PYs (95% CI: 0.10-0.26) in the reference group. The risk of HCV reinfection in patients on haemodialysis was comparable to that in the reference patients (hazard ratio [HR]: 1.39; 95% CI: 0.44-4.38, P = 0.57). CONCLUSIONS The risk of HCV reinfection in patients on haemodialysis who achieve SVR12 is low and comparable to that in the low-risk general population. HCV microelimination in this special population is feasible once universal screening and scaled-up treatment are implemented.
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Liu CH, Chen CY, Su WW, Tseng KC, Lo CC, Liu CJ, Chen JJ, Peng CY, Shih YL, Yang SS, Huang CS, Huang KJ, Chang CY, Tsai MC, Kao WY, Fang YJ, Chen PY, Su PY, Tseng CW, Huang JJ, Lee PL, Lai HC, Hsieh TY, Chang CH, Huang YJ, Lee FJ, Chang CC, Kao JH. Sofosbuvir/velpatasvir with or without low-dose ribavirin for patients with chronic hepatitis C virus infection and severe renal impairment. Gut 2022; 71:176-184. [PMID: 33408122 DOI: 10.1136/gutjnl-2020-323569] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Revised: 12/21/2020] [Accepted: 12/23/2020] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Data regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) with or without low-dose ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection and severe renal impairment (RI) are limited. We evaluated the performance of SOF/VEL with or without low-dose RBV in HCV-infected patients with chronic kidney disease stage 4 or 5. DESIGN 191 patients with compensated (n=181) and decompensated (n=10) liver diseases receiving SOF/VEL (400/100 mg/day) alone and SOF/VEL with low-dose RBV (200 mg/day) for 12 weeks were retrospectively recruited at 15 academic centres in Taiwan. The effectiveness was determined by sustained virological response at off-treatment week 12 (SVR12) in evaluable (EP) and per-protocol populations (PP). The safety profiles were assessed. RESULTS The SVR12 rates by EP and PP analyses were 94.8% (95% CI 90.6% to 97.1%) and 100% (95% CI 97.9% to 100%). In patients with compensated liver disease, the SVR12 rates were 95.0% and 100% by EP and PP analyses. In patients with decompensated liver disease, the SVR12 rates were 90.0% and 100% by EP and PP analyses. Ten patients who failed to achieve SVR12 were attributed to non-virological failures. Among the 20 serious adverse events (AEs), none were judged related to SOF/VEL or RBV. The AEs occurring in ≥10% included fatigue (14.7%), headache (14.1%), nausea (12.6%), insomnia (12.0%) and pruritus (10.5%). None had ≥grade 3 total bilirubin or alanine aminotransferase elevations. CONCLUSION SOF/VEL with or without low-dose RBV is effective and well-tolerated in HCV-infected patients with severe RI.
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Affiliation(s)
- Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan
| | - Wei-Wen Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.,School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Ching-Chu Lo
- Department of Internal Medicine, St. Martin De Porres Hospital, Daya, Chiayi, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Jyh-Jou Chen
- Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Liouying, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.,School of Medicine, China Medical University, Taichung, Taiwan
| | - Yu-Lueng Shih
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.,School of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan
| | - Chia-Sheng Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yang Ming Hospital, Chiayi, Taiwan
| | - Ke-Jhang Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Beigang Hospital, Yunlin, Taiwan
| | - Chi-Yang Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Fu Jen Catholic University Hospital, Taipei, Taiwan
| | - Ming-Chang Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Wei-Yu Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yo-Jen Fang
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan
| | - Po-Yueh Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan
| | - Pei-Yuan Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Chih-Wei Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.,School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Jow-Jyh Huang
- Department of Internal Medicine, St. Martin De Porres Hospital, Daya, Chiayi, Taiwan
| | - Pei-Lun Lee
- Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Liouying, Taiwan
| | - Hsueh-Chou Lai
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.,School of Medicine, China Medical University, Taichung, Taiwan
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chung-Hsin Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Yi-Jie Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Fu-Jen Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Fu Jen Catholic University Hospital, Taipei, Taiwan
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, 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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Su PY, Chen YY, Lai JH, Chen HM, Yao CT, Liu IL, Zeng YH, Huang SP, Hsu YC, Wu SS, Siao FY, Yen HH. Real-World Experience of Chronic Hepatitis C-Related Compensated Liver Cirrhosis Treated with Glecaprevir/Pibrentasvir: A Multicenter Retrospective Study. J Clin Med 2021; 10:jcm10225236. [PMID: 34830518 PMCID: PMC8619604 DOI: 10.3390/jcm10225236] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 11/05/2021] [Accepted: 11/09/2021] [Indexed: 12/18/2022] Open
Abstract
Background: Glecaprevir/pibrentasvir is a protease inhibitor-containing pangenotypic direct-acting antiviral regimen that has been approved for the treatment of chronic hepatitis C. The present study aimed to evaluate the safety and efficacy of glecaprevir/pibrentasvir in patients with compensated cirrhosis in a real-world setting. Methods: We evaluated the real-world safety and efficacy of glecaprevir/pibrentasvir in patients with compensated cirrhosis from five hospitals in the Changhua Christian Care System, who underwent treatment between August 2018 and October 2020. The primary endpoint was a sustained virological response observed 12 weeks after completion of the treatment. Results: Ninety patients, including 70 patients who received the 12-week therapy and 20 patients who received the 8-week therapy, were enrolled. The mean age of the patients was 65 years, and 57.8% of the patients were males. Sixteen (17.8%) patients had end-stage renal disease, and 15 (16.7%) had co-existing hepatoma. The hepatitis C virus genotypes 1 (40%) and 2 (35.6%) were most common. The common side effects included anorexia (12.2%), pruritus (7.8%), abdominal discomfort (7.8%), and malaise (7.8%). Laboratory adverse grade ≥3 events included anemia (6.3%), thrombocytopenia (5.1%), and jaundice (2.2%). The overall sustained virological response rates were 94.4% and 97.7% in the intention-to-treat and per-protocol analyses, respectively. Conclusions: the glecaprevir/pibrentasvir treatment regimen was highly effective and well tolerated among patients with compensated cirrhosis in the real-world setting.
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Affiliation(s)
- Pei-Yuan Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Yang-Yuan Chen
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
- Division of Gastroenterology, Department of Internal Medicine, Yuanlin Christian Hospital, Changhua 500, Taiwan
- Department of Hospitality, MingDao University, Changhua 500, Taiwan
| | - Jun-Hung Lai
- Division of Gastroenterology, Department of Internal Medicine, Erhlin Christian Hospital, Changhua 500, Taiwan;
| | - Hung-Ming Chen
- Division of Gastroenterology, Department of Internal Medicine, Yunlin Christian Hospital, Yunlin 648, Taiwan;
| | - Chih-Ta Yao
- Division of Gastroenterology, Department of Internal Medicine, Lukang Christian Hospital, Changhua 500, Taiwan;
| | - I-Ling Liu
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Ya-Huei Zeng
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Siou-Ping Huang
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Yu-Chun Hsu
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Shun-Sheng Wu
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Fu-Yuan Siao
- Department of Emergency Medicine, Changhua Christian Hospital, Changhua 500, Taiwan;
- Department of Kinesiology, Health and Leisure, Chienkuo Technology University, Changhua 500, Taiwan
| | - Hsu-Heng Yen
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
- Artificial Intelligence Development Center, Changhua Christian Hospital, Changhua 500, Taiwan
- General Education Center, Chienkuo Technology University, Changhua 500, Taiwan
- Department of Electrical Engineering, Chung Yuan University, Taoyuan 320, Taiwan
- College of Medicine, National Chung Hsing University, Taichung 400, Taiwan
- Correspondence: ; Tel.: +886-4-723-8595-5501
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8
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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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9
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Yen HH, Su PY, Liu IL, Zeng YY, Huang SP, Hsu YC, Yang CW, Chen YY. Direct-acting antiviral treatment for Hepatitis C Virus in geriatric patients: a real-world retrospective comparison between early and late elderly patients. PeerJ 2021; 9:e10944. [PMID: 33777520 PMCID: PMC7977377 DOI: 10.7717/peerj.10944] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 01/24/2021] [Indexed: 12/29/2022] Open
Abstract
Introduction Chronic hepatitis C virus (HCV) infection rates are high in the geriatric population considering that interferon-based therapy is usually intolerable. With the introduction of oral antiviral therapy for HCV, increased treatment tolerability and good treatment responses have been observed. However, treatment data regarding the geriatric population have been limited. Therefore, this retrospective study aimed to evaluate the efficacy and safety of direct-acting antiviral therapy for HCV in the geriatric population. Materials and Methods The primary end point was sustained virologic response (SVR) 12 weeks after treatment completion, whereas the secondary end points were treatment-related side effects and short-term survival rate following treatment. Results In total, 492 patients (median age, 73 years; 43.9% males), including 278 early elderly patients, were enrolled. Among the included patients, 45% had cirrhosis. HCV genotypes 1 (72.4%) and 2 (25.4%) were the most common. The overall SVR rate was 96.7%, with no difference in SVR rates observed between early and late elderly groups (96.8% vs. 96.7%; p = 0.983). Both groups showed similar side effects, including dizziness (11.4%), and fatigue (8.7%), with three patients discontinuing therapy owing to side effects. Both groups had a similar 3-year survival rate. Significant factors associated with post-treatment survival included cirrhosis, albumin, and creatinine level. Conclusions Our real-world data showed that both early and late elderly patients could undergo direct-acting antiviral treatment for HCV with excellent treatment outcomes.
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Affiliation(s)
- Hsu-Heng Yen
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan.,General Educational Center, Chienkuo Technology University, Changhua, Taiwan.,Institute of Medicine, Chung Shan Medical and Dental College, Taichung, Taiwan
| | - Pei-Yuan Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - I-Ling Liu
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Ya-Yuei Zeng
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Siou-Ping Huang
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Yu-Chun Hsu
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Chia-Wei Yang
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Yang-Yuan Chen
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
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10
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Hsu PY, Wei YJ, Lee JJ, Niu SW, Huang JC, Hsu CT, Jang TY, Yeh ML, Huang CI, Liang PC, Lin YH, Hsieh MY, Hsieh MH, Chen SC, Dai CY, Lin ZY, Chen SC, Huang JF, Chang JM, Hwang SJ, Chuang WL, Huang CF, Chiu YW, Yu ML. Comedications and potential drug-drug interactions with direct-acting antivirals in hepatitis C patients on hemodialysis. Clin Mol Hepatol 2020; 27:186-196. [PMID: 33317251 PMCID: PMC7820195 DOI: 10.3350/cmh.2020.0180] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Accepted: 09/30/2020] [Indexed: 02/07/2023] Open
Abstract
Background/Aims Direct‐acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population. Methods The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan. Results Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10). Conclusions HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.
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Affiliation(s)
- Po-Yao Hsu
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Division of Hepatobiliary, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yu-Ju Wei
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Division of Hepatobiliary, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jia-Jung Lee
- Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Sheng-Wen Niu
- Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jiun-Chi Huang
- Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Cheng-Ting Hsu
- Division of Hepatobiliary, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tyng-Yuan Jang
- Division of Hepatobiliary, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Division of Hepatobiliary, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-I Huang
- Division of Hepatobiliary, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Cheng Liang
- Division of Hepatobiliary, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hung Lin
- Division of Hepatobiliary, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Division of Hepatobiliary, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Division of Hepatobiliary, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Szu-Chia Chen
- Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Division of Hepatobiliary, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Division of Hepatobiliary, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Division of Hepatobiliary, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Division of Hepatobiliary, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jer-Ming Chang
- Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shang-Jyh Hwang
- Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Division of Hepatobiliary, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Division of Hepatobiliary, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Wen Chiu
- Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Division of Hepatobiliary, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
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11
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Yen HH, Su PY, Zeng YH, Liu IL, Huang SP, Hsu YC, Chen YY, Yang CW, Wu SS, Chou KC. Glecaprevir-pibrentasvir for chronic hepatitis C: Comparing treatment effect in patients with and without end-stage renal disease in a real-world setting. PLoS One 2020; 15:e0237582. [PMID: 32790715 PMCID: PMC7425913 DOI: 10.1371/journal.pone.0237582] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 07/29/2020] [Indexed: 12/12/2022] Open
Abstract
Introduction Chronic hepatitis C virus (HCV) infection is increasingly observed in patients with renal disease. With the introduction of glecaprevir/pibrentasvir (GLE/PIB) as a pan-genotype therapy for HCV, treatment efficacy is expected to rise. Materials and methods This retrospective study evaluated the efficacy and safety of GLE/PIB treatment in adults with HCV infection and end-stage renal disease (ESRD). The primary end point was sustained virological response (SVR) observed 12 weeks after completed treatment. Results We enrolled 235 patients, including 44 patients with ESRD. Median age was 60 years, and 48% were males. Twenty-two percent had cirrhosis. HCV genotypes 1 (43%) and 2 (41%) were the most common. The overall SVR rate was 96.6%. Patients with ESRD were older than those without (67.6 years vs 58.3 years, p < 0.001) and trended toward having a higher prevalence of cirrhosis (32% vs 19%, p = 0.071). A significant proportion of patients with ESRD complained of skin itching during treatment (61% vs 26%, p < 0.001), and the SVR rate were similar between these two groups (95.45% vs 96.86%, p = 0.644). Conclusions Despite a higher rate of pruritus among patients with ESRD, GLE/PIB-based therapy achieved similarly high SVR rates among patients with and without ESRD.
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Affiliation(s)
- Hsu-Heng Yen
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- General Education Center, Chienkuo Technology University, Changhua, Taiwan
- * E-mail: , (HHY); (KCC)
| | - Pei-Yuan Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Ya-Huei Zeng
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - I-Ling Liu
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Siou-Ping Huang
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Yu-Chun Hsu
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Yang-Yuan Chen
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Chia-Wei Yang
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Shun-Sheng Wu
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Kun-Ching Chou
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
- * E-mail: , (HHY); (KCC)
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12
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Elbasvir/grazoprevir for hepatitis C virus genotype 1b East-Asian patients receiving hemodialysis. Sci Rep 2020; 10:9180. [PMID: 32513953 PMCID: PMC7280513 DOI: 10.1038/s41598-020-66182-8] [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: 01/22/2020] [Accepted: 05/12/2020] [Indexed: 11/26/2022] Open
Abstract
Data regarding the efficacy and tolerability of elbasvir/grazoprevir (EBR/GZR) for East-Asian hepatitis C virus genotype 1b (HCV GT1b) patients receiving hemodialysis were limited. We prospectively recruited 40 HCV GT1b hemodialysis patients who received EBR/GZR for 12 weeks at 6 academic centers in Taiwan. The efficacy endpoints were sustained virologic response 12 weeks off-therapy (SVR12) by intention-to-treat (ITT) modified ITT (mITT) analyses. Patients’ baseline characteristics, early viral kinetics and HCV resistance-associated substitutions (RASs) at HCV non-structural 3 and 5 A (NS3 and NS5A) regions potentially affecting SVR12 were analyzed. The tolerability for EBR/GZR was also assessed. The SVR12 rates by ITT and mITT analyses were 95% (38 of 40 patients; 95% confidence interval (CI): 83.5–98.6%) and 100% (38 of 38 patients; 95% CI: 90.8–100%), respectively. Patients’ baseline characteristics, on-treatment viral decline, and baseline HCV RASs did not affect SVR12. All patients tolerated treatment well. Among 5 patients who had serious adverse events (AEs) including one death due to on-treatment suicide and the other death due to off-therapy acute myocardial infarction, none of these events were judged related to EBR/GZR. The common AEs included upper respiratory tract infection (7.5%), fatigue (5.0%) and anorexia (5.0%). Nine (22.5%) and 8 (20.0%) patients had on-treatment hemoglobin levels of 9.0–10.0 g/dL and 7.0–9.0 g/dL. Three (7.5%) patients had on-treatment elevated alanine aminotransferase (ALT) quotient > 2.5, in whom one (2.5%) had EBR/GZR-induced late ALT elevation. No patients developed hyperbilirubinemia or hepatic decompensation. In conclusion, treatment with EBR/GZR is effective and well-tolerated for East-Asian HCV GT1b patients receiving hemodialysis.
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13
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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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14
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Cheema SUR, Rehman MS, Hussain G, Cheema SS, Gilani N. Efficacy and tolerability of sofosbuvir and daclatasvir for treatment of hepatitis C genotype 1 & 3 in patients undergoing hemodialysis- a prospective interventional clinical trial. BMC Nephrol 2019; 20:438. [PMID: 31779583 PMCID: PMC6883698 DOI: 10.1186/s12882-019-1631-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 11/20/2019] [Indexed: 12/14/2022] Open
Abstract
Background There is paucity of data using direct anti-viral agents (DAA) in patients on maintenance hemodialysis (MHD) infected with HCV-genotype 1 & 3. Aim of the study was to evaluate DAA therapy in patients infected with HCV-genotype 1 & 3 on MHD. Methods A prospective open label, parallel, non-randomized interventional trial was conducted in patients with Hepatitis-C on maintenance hemodialysis. Total of Sixty two (62) patients with hepatitis-C on maintenance hemodialysis were screened and 36 patients were enrolled and then equally allocated in 1:1 ratio to group 1 who received 400 mg daily sofosbuvir/ 60 mg daily daclatasvir and group 2 who received thrice a week 400 mg Sofosbuvir and daily 60 mg daclatasvir for 12 weeks. Patients with compensated cirrhosis received therapy for 24 weeks. Relevant data was obtained before, during and after therapy. HCV viral load was assessed at week 4, 8, at end of therapy and 12 weeks after treatment. Results Eighteen (18) patients were allocated in each group. Three patients in group 1 withdrawn from the study after 2 weeks due to refusal to participate, while one withdrawn in group 2 due to development of adverse effect. Mean age of patients was 47.22 + 14.17 in group 1 and 53.89 + 14.11 in group 2. Genotype 3 was most common in group 1 patients, n = 12 (66.6%), and n = 11 (61.1%) in group 2. All patients in both groups achieved undetectable viral load at 12th week. As per intention to treat analysis overall 29/36 (80.55%) patients achieved SVR (group 1 = 15/18; group 2 = 14/18) and as per-protocol analysis overall 29/32 (90.62%) patients achieved SVR (group 1 = 15/15; group 2 = 14/17). Conclusion Direct acting antiviral therapy using sofosbuvir and declatsavir is highly effective and tolerable in patients with HCV genotype 1 & 3 undergoing maintenance hemodialysis, especially when given daily. Trial registration This trial is registered in WHO, International Clinical Trial Registry Platform, through Iranian Registry of Clinical Trials (IRCT) having IRCT ID: IRCT20170614034526N3, registered retrospectively on 2019-03-08.
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Affiliation(s)
| | - Muhammad Salman Rehman
- Department of Gastroenterology Jinnah Hospital & Allama Iqbal Medical College, Lahore, Pakistan
| | - Ghulam Hussain
- Department of Gastroenterology Jinnah Hospital & Allama Iqbal Medical College, Lahore, Pakistan
| | | | - Nooman Gilani
- Department of Gastroenterology Jinnah Hospital & Allama Iqbal Medical College, Lahore, Pakistan
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15
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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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16
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Radhakrishnan RC, Gopal B, Zachariah UG, Abraham P, Mohapatra A, Valson AT, Alexander S, Jacob S, Tulsidas KS, David VG, Varughese S. The long-term impact of hepatitis C infection in kidney transplantation in the pre-direct acting antiviral era. SAUDI JOURNAL OF KIDNEY DISEASES AND TRANSPLANTATION 2019; 29:1092-1099. [PMID: 30381505 DOI: 10.4103/1319-2442.243964] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Hepatitis C virus (HCV) infection in kidney transplantation is an important issue with effects on patient and graft survival. The current standard of care involves using oral Direct Acting Antiviral drugs. Till recently, pre-transplant treatment with interferon was the only option for treatment. We studied 677 consecutive kidney transplant recipients with HCV infection. 5.2% patients had evidence of HCV infection. 2.0% were newly detected to have HCV infection after transplant (de novo HCV group). Nearly 28.6% had negative antibody tests but positive Nucleic Acid Test at the time of diagnosis. Eighty-five percent of pre-transplant HCV-positive patients were treated with interferon-based regimens. Early virologic response was seen in 66.6%. End of treatment response was achieved by 94.1%. Sustained virologic response was seen in 81.2%. Overall, patient and graft survival were not different between HCV and control groups (log-rank P = 0.154). Comparing HCV and control groups, there was a tendency toward increased fungal (11.4% vs. 5.6%, P = 0.144) and CMV infections (25.7% vs. 17.1%, P = 0.191) in the HCV group, though it did not reach statistical significance. Eighty-percent of the interferon-treated patients suffered side effects. On comparing, the pre-transplant HCV-positive group (85% treated) with the de novo HCV group (none treated), the de novo group had significantly reduced patient survival (P = 0.020) and NODAT (35.7 vs 4.8%, P = 0.028), and a tendency toward higher CMV infections (35.7% vs 19%, P = 0.432). In addition, death and hepatic complications (decompensated liver disease, fibrosing cholestatic hepatitis) occurred only in de novo HCV group. These results highlight the need for continued post-transplant treatment of HCV positive patients. The newer anti-HCV drugs are expected to fulfill this felt-need in kidney transplantation but long-term results are awaited. This study can serve as a benchmark for future studies to compare the long-term effect of Direct Acting Antiviral drugs.
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Affiliation(s)
| | - Basu Gopal
- Central Northern Adelaide Renal and Transplant Service, Royal Adelaide Hospital, Adelaide, Australia
| | - Uday G Zachariah
- Department of Hepatology, Christian Medical College, Vellore, India
| | - Priya Abraham
- Department of Clinical Virology, Christian Medical College, Vellore, India
| | - Anjali Mohapatra
- Department of Nephrology, Christian Medical College, Vellore, India
| | - Anna T Valson
- Department of Nephrology, Christian Medical College, Vellore, India
| | | | - Shibu Jacob
- Department of Nephrology, Christian Medical College, Vellore, India
| | | | - Vinoi G David
- Department of Nephrology, Christian Medical College, Vellore, India
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17
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Cohen-Bucay A, Francis JM, Gordon CE. Timing of hepatitis C virus infection treatment in kidney transplant candidates. Hemodial Int 2019; 22 Suppl 1:S61-S70. [PMID: 29694723 DOI: 10.1111/hdi.12643] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Hepatitis C virus (HCV) infection is prevalent in patients with kidney disease including transplant candidates and recipients. It is associated with increased morbidity and mortality in end-stage renal disease patients and also increases the risk of allograft rejection and decreases allograft and patient survival post-transplant. Newly developed direct acting antivirals have revolutionized the way HCV is treated. Whether patients are treated before or after kidney transplantation, the cure rates with direct acting antivirals are >90%. Great debate has formed revolving the optimal timing to treat kidney transplant candidates. On the one hand, treatment before transplantation decreases early post-transplant complications related to HCV. On the other, postponing treatment until after transplantation opens the possibility of transplanting a kidney from a HCV positive donor, which is associated with shorter waiting time and improved organ utilization by expanding the organ donor pool. Most patients living in an area where waiting time is reduced by accepting an HCV positive kidney would benefit by the strategy of treatment post-transplantation, but this decision needs to be individualized in a patient-by-patient basis given that there are special circumstances (i.e., severe HCV-related extrahepatic manifestations, availability of live donors, etc.) in which treatment before transplant might be preferred.
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Affiliation(s)
- Abraham Cohen-Bucay
- Renal Section, Boston University Medical Center, Boston, Massachusetts, USA.,Division of Nephrology and Transplant Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Jean M Francis
- Renal Section, Boston University Medical Center, Boston, Massachusetts, USA
| | - Craig E Gordon
- Renal Section, Boston University Medical Center, Boston, Massachusetts, USA
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18
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Nakashima M, Toyoda H, Tada T, Mizuno K, Iio E, Tanaka Y, Sugiyama T, Yoshimura T, Kumada T. Influence of renal dysfunction on dose reduction and virologic efficacy of regimens combining ribavirin and all-oral direct acting antivirals in patients with chronic hepatitis C virus infection. Hepatol Res 2019; 49:512-520. [PMID: 30628746 DOI: 10.1111/hepr.13311] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Revised: 12/25/2018] [Accepted: 12/26/2018] [Indexed: 12/28/2022]
Abstract
AIM Several interferon (IFN)-free, all-oral regimens with direct acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection also include ribavirin (RBV). We investigated the influence of renal dysfunction on virologic efficacy and adverse effects in 189 patients with HCV genotype 2 infection who received combination RBV-DAA regimens. METHODS The incidence of RBV-induced anemia, RBV dose reduction, and virologic efficacy were compared according to baseline renal function as defined by the estimated glomerular filtration rate (eGFR). RESULTS Patients with renal dysfunction (eGFR = 30-59 mL/min/1.73 m2 ) had higher rate of RBV dose reduction and more marked decreases in hemoglobin levels. These findings were more pronounced in patients with the ITPA CC genotype, who are more sensitive to RBV-induced anemia. Although there were no statistically significant differences in sustained virologic response (SVR) rates according to renal function overall (P = 0.1650), the SVR rate was significantly lower in patients who required RBV dose reduction than in those who did not (P < 0.0001). CONCLUSIONS Baseline renal dysfunction could unfavorably affect the outcomes of RBV-DAA in patients with chronic HCV infection due to the increased risk of RBV dose reduction, even in the era of IFN-free DAA regimens.
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Affiliation(s)
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Toshifumi Tada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Kazuyuki Mizuno
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Etsuko Iio
- Department of Virology and Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan
| | - Tadashi Sugiyama
- Laboratory of Pharmacy Practice and Social Science, Gifu Pharmaceutical University, Gifu, Japan
| | | | - Takashi Kumada
- Department of Nursing, Ogaki Women's College, Ogaki, Japan
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19
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Lee BS, Song MJ, Kwon JH, Lee TH, Jang JW, Kim SH, Lee SH, Kim HS, Kim JH, Kim SB, Ko SY, Song DS. Efficacy and Safety of Daclatasvir and Asunaprevir in Patients with Hepatitis C Virus Genotype 1b Infection on Hemodialysis. Gut Liver 2019; 13:191-196. [PMID: 30400729 PMCID: PMC6430432 DOI: 10.5009/gnl18240] [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] [Received: 05/28/2018] [Revised: 07/09/2018] [Accepted: 08/13/2018] [Indexed: 12/13/2022] Open
Abstract
Background/Aims We evaluated the efficacy and safety of daclatasvir (DCV) and asunaprevir (ASV) in patients with chronic hepatitis C virus (HCV) infection on hemodialysis. Methods; We performed a single-arm, multicenter prospective study. Twenty-one chronic hemodialysis patients with HCV infection were prospectively enrolled from February 2016 to April 2017. We evaluated the virological responses at weeks 4, 12, and 24 (end of treatment [EOT]) and the sustained virological response at 12 weeks after the EOT (SVR12). The tolerability and safety of the drugs were also assessed. Results None of the 20 patients had the NS5A resistance-associated variant (NS5A RAV), and one patient was indeterminate for the NS5A RAV. Seventeen patients (80%) completed the 24 weeks of treatment with DCV and ASV. Four patients discontinued the study prior to week 12. In an intention-to-treat analysis, the SVR12 was 76.1%. In a per-protocol analysis, patients who completed DCV and ASV treatment achieved an SVR12 of 100%. DCV and ASV were well tolerated by the majority of patients. Three patients discontinued treatment due to adverse events (AEs) including dizziness, dyspnea, and neutropenia. The patient with indeterminate NS5A RAV showed viral breakthrough and discontinued treatment. Conclusions DCV and ASV combination therapy in chronic hemodialysis patients with HCV infection achieved a high SVR12 rate with few AEs. To maximize the SVR12 rate, it is important to identify candidates by baseline RAV testing. Close monitoring of the safety and tolerability of DCV and ASV may be necessary in HCV-infected patients on hemodialysis. (ClinicalTrials.gov ID NCT02580474).
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Affiliation(s)
- Byung Seok Lee
- Department of Internal Medicine, Chungnam University College of Medicine, Seoul,
Korea
| | - Myeong Jun Song
- Division of Hepatology, Department of Internal Medicine, Daejeon St. Mary’s Hospital, 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
| | - Tae Hee Lee
- Department of Internal Medicine, Konyang University College of Medicine, Daejeon,
Korea
| | - Ji Woong Jang
- Department of Internal Medicine, Eulji University Hospital, Eulji University College of Medicine, Daejeon,
Korea
| | - Seok Hyun Kim
- Department of Internal Medicine, Chungnam University College of Medicine, Seoul,
Korea
| | - Sae Hwan Lee
- Department of Internal Medicine, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Cheonan,
Korea
| | - Hong Soo Kim
- Department of Internal Medicine, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Cheonan,
Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul,
Korea
| | - Seok Bae Kim
- Department of Internal Medicine, Dankook University Hospital, Dankook University College of Medicine, Cheonan,
Korea
| | - Soon Young Ko
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul,
Korea
| | - Do Seon Song
- Division of Hepatology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
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20
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Taneja S, Duseja A, De A, Kumar V, Ramachandran R, Sharma A, Dhiman RK, Gupta KL, Chawla Y. Successful treatment of chronic hepatitis C infection with directly acting antivirals in renal transplant recipients. Nephrology (Carlton) 2018; 23:876-882. [PMID: 28703905 DOI: 10.1111/nep.13109] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/30/2017] [Indexed: 12/15/2022]
Abstract
AIMS The data regarding the treatment of chronic hepatitis C (CHC) in renal transplant recipients is lacking from the Asia-Pacific region. The aim of the present study was to assess the safety and efficacy of directly acting antivirals (DAAs) in the treatment of CHC infection in renal transplant recipients. METHODS A total of 47 CHC infected renal transplant recipients were enrolled in this real life observational cohort analysis between March 2015 and September 2016. Presence of hepatic fibrosis/cirrhosis was assessed on transient elastography (Fibroscan). Fourteen patients were treated with Sofosbuvir and Ribavirin for 24 weeks. Twenty-two patients received Sofosbuvir and Ledipasvir and 12 patients received Sofosbuvir and Daclatasvir with (n = 3) or without (n = 31) Ribavirin for 12 or 24 weeks depending on genotype and underlying cirrhosis. Data were analyzed for safety and treatment efficacy [sustained virological response at 12 weeks (SVR12)]. RESULTS The median baseline HCV RNA concentration in the whole group was 7.38 × 106 IU/mL (1.23 × 104 -6.36 × 107 ). The SVR12 rates were 100% in all groups except in the Sofosbuvir and Ribavirin group (86%). Transient Elastography revealed minimal or no fibrosis (F0-F1) in 31 (65.96%) patients, moderate fibrosis (F2) in 11 (23.4%) patients and cirrhosis in five (10.64%) patients. The only serious adverse effect was anaemia observed in eight (57%) patients in the Sofosbuvir and Ribavirin group. CONCLUSION DAAs including Sofosbuvir, Daclatasvir and Ledipasvir with or without ribavirin are safe and effective for the treatment of chronic hepatitis C in renal transplant recipients.
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Affiliation(s)
- Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Arka De
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Vivek Kumar
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Raja Ramachandran
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashish Sharma
- Department of Transplant Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Radha K Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Krishan L Gupta
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Yogesh Chawla
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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21
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Maduell F, Belmar L, Ugalde J, Laguno M, Martínez-Rebollar M, Ojeda R, Arias M, Rodas L, Rossi F, Llovet LP, González LN, Mallolas J, Londoño MC. Elimination of hepatitis C virus infection from a hemodialysis unit and impact of treatment on the control of anemia. GASTROENTEROLOGIA Y HEPATOLOGIA 2018; 42:164-170. [PMID: 30293914 DOI: 10.1016/j.gastrohep.2018.07.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Revised: 07/23/2018] [Accepted: 07/29/2018] [Indexed: 12/13/2022]
Abstract
INTRODUCTION In the interferon era, the treatment of hepatitis C virus (HCV) infection in patients on haemodialysis (HD) was limited due to the significant number of treatment-related adverse events (AEs). Direct-acting antivirals (DAAs) have demonstrated their efficacy and safety in the treatment of HCV in patients with advanced chronic kidney disease on haemodialysis. The objective of the study was to evaluate the success in eliminating HCV infection from our dialysis unit using DAAs, and to assess the impact of HCV elimination on clinical and analytical outcomes. PATIENTS AND METHODS This is a prospective, interventional, single-center study at Hospital Clínic de Barcelona. All HCV-RNA positive patients who received antiviral therapy with DAAs within a 3-year period (2014-2017) were analyzed (n=20). Data on virologic response, adverse events, and biochemical and hematological parameters during and after DAA therapy were analyzed. RESULTS All patients achieved sustained virologic response (SVR) and only 40% of patients presented with mild AEs. None of the patients presented with HCV reinfection after a 1-year follow-up period, and thus HCV was eliminated from our HD unit. SVR was associated with a significant increase in hemoglobin and hematocrit, and a tendency toward the need for lower doses of iron supplementation with no changes in darbepoetin dose. CONCLUSION HCV infection can be safely eliminated from HD units with the use of DAAs, preventing new infections in patients and healthcare staff. In the short term, the achievement of SVR is associated with an improvement in the control of anemia.
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Affiliation(s)
- Francesc Maduell
- Department of Nephrology, Hospital Clínic Barcelona, Barcelona, Spain
| | - Lara Belmar
- Department of Nephrology, Hospital Clínic Barcelona, Barcelona, Spain
| | - Jésica Ugalde
- Department of Nephrology, Hospital Clínic Barcelona, Barcelona, Spain
| | - Montserrat Laguno
- HIV/AIDS Unit, Infectious Disease Service, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - María Martínez-Rebollar
- HIV/AIDS Unit, Infectious Disease Service, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Raquel Ojeda
- Department of Nephrology, Hospital Clínic Barcelona, Barcelona, Spain
| | - Marta Arias
- Department of Nephrology, Hospital Clínic Barcelona, Barcelona, Spain
| | - Lida Rodas
- Department of Nephrology, Hospital Clínic Barcelona, Barcelona, Spain
| | - Florencia Rossi
- Department of Nephrology, Hospital Clínic Barcelona, Barcelona, Spain
| | - Laura-Patricia Llovet
- Liver Unit, Hospital Clínic Barcelona, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
| | | | - Josep Mallolas
- HIV/AIDS Unit, Infectious Disease Service, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Maria-Carlota Londoño
- Liver Unit, Hospital Clínic Barcelona, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain.
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22
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Salvadori M, Tsalouchos A. Hepatitis C and renal transplantation in era of new antiviral agents. World J Transplant 2018; 8:84-96. [PMID: 30148074 PMCID: PMC6107518 DOI: 10.5500/wjt.v8.i4.84] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Revised: 04/17/2018] [Accepted: 05/30/2018] [Indexed: 02/05/2023] Open
Abstract
Data from World Health Organization estimates that the hepatitis C virus (HCV) prevalence is 3% and approximately 71 million persons are infected worldwide. HCV infection is particularly frequent among patients affected by renal diseases and among those in dialysis treatment. In addition to produce a higher rate of any cause of death, HCV in renal patients and in renal transplanted patients produce a deterioration of liver disease and is a recognized cause of transplant glomerulopathy, new onset diabetes mellitus and lymphoproliferative disorders. Treatment of HCV infection with interferon alpha and/or ribavirin had a poor efficacy. The treatment was toxic, expensive and with limited efficacy. In the post-transplant period was also cause of severe humoral rejection. In this review we have highlighted the new direct antiviral agents that have revolutionized the treatment of HCV both in the general population and in the renal patients. Patients on dialysis or with low glomerular filtration rate were particularly resistant to the old therapies, while the direct antiviral agents allowed achieving a sustained viral response in 90%-100% of patients with a short period of treatment. This fact to date allows HCV patients to enter the waiting list for transplantation easier than before. These new agents may be also used in renal transplant patients HCV-positive without relevant clinical risks and achieving a sustained viral response in almost all patients. New drug appears in the pipeline with increased profile of efficacy and safety. These drugs are now the object of several phases II, III clinical trials.
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Affiliation(s)
- Maurizio Salvadori
- Department of Transplantation Renal Unit, Careggi University Hospital, Florence 50139, Italy
| | - Aris Tsalouchos
- Nephrology and Dialysis Unit, Saints Cosmas and Damian Hospital, Pescia 51017, Italy
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23
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Kim SM, Song IH. Hepatitis C virus infection in chronic kidney disease: paradigm shift in management. Korean J Intern Med 2018; 33:670-678. [PMID: 29961309 PMCID: PMC6030406 DOI: 10.3904/kjim.2018.202] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Accepted: 06/17/2018] [Indexed: 12/14/2022] Open
Abstract
Hepatitis C virus (HCV) infection in chronic kidney disease (CKD) is associated with increased liver-related morbidity and mortality rates, accelerated progression to end-stage renal disease, and risk of cardiovascular events. CKD patients with HCV infection require antiviral therapy. Pegylated interferon (peg-IFN) plus ribavirin was the standard of care for HCV-infected CKD patients before the introduction of first-generation direct-acting antiviral (DAA) oral anti-HCV agents. Peg-IFN-based treatment has a low virologic response rate and poor compliance, resulting in a high dropout rate. Recently, several clinical trials of all-DAA combination regimens have reported excellent antiviral efficacy and few adverse drug reactions in HCV-infected patients with CKD. These positive results have revolutionized the treatment of chronic HCV infection in this population. In this review, we address the impact of chronic HCV infection in CKD patients, and discuss their management using next-generation DAAs.
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Affiliation(s)
- So Mi Kim
- Division of Nephrology, Department of Internal Medicine, Dankook University Hospital, Cheonan, Korea
| | - Il Han Song
- Division of Hepatology, Department of Internal Medicine, Dankook University Hospital, Cheonan, Korea
- Correspondence to Il Han Song, M.D. Division of Hepatology, Department of Internal Medicine, Dankook University Hospital, 201 Manghyang-ro, Dongnam-gu, Cheonan 31116, Korea Tel: +82-41-5503924 Fax: +82-41-5563256 E-mail:
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Maughan A, Ogbuagu O. Pegylated interferon alpha 2a for the treatment of hepatitis C virus infection. Expert Opin Drug Metab Toxicol 2018; 14:219-227. [PMID: 29271660 DOI: 10.1080/17425255.2018.1421173] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Treatments for hepatitis C virus (HCV) infection have advanced rapidly in the last decade. Pegylated interferon alpha 2a (PEG-IFN alpha 2a) alone, in combination with ribavirin and with or without direct acting antivirals (DAAs) is modestly effective in the treatment of chronic HCV infection. Areas covered: The review describes the chemistry, pharmacokinetic and pharmacodynamic properties, clinical efficacy, safety and drug-drug interaction profiles of PEG-IFN alpha 2a. Expert opinion: Despite the availability of DAAs and its formidable toxicity profile, PEG-IFN alpha 2a retains a role for the treatment of acute HCV and chronic HCV infection in resource limited settings and for end-stage renal disease patients and others who cannot access DAAs or are DAA-ineligible. Knowledge of pharmacogenetic profiles which favor successful treatment outcomes with IFN-based therapies may allow for selection of best candidates for the regimen.
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Affiliation(s)
- Ashly Maughan
- a Yale AIDS Program, Section of Infectious Diseases , Yale University School of Medicine , New Haven , CT , USA
| | - Onyema Ogbuagu
- a Yale AIDS Program, Section of Infectious Diseases , Yale University School of Medicine , New Haven , CT , USA
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Huang Y, Li MH, Hou M, Xie Y. Peginterferon alfa-2a for the treatment of chronic hepatitis C in the era of direct-acting antivirals. Hepatobiliary Pancreat Dis Int 2017; 16:470-479. [PMID: 28992878 DOI: 10.1016/s1499-3872(17)60044-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Accepted: 06/23/2017] [Indexed: 02/05/2023]
Abstract
BACKGROUND The availability of novel direct-acting antivirals (DAAs) represents a new era of curative hepatitis C virus (HCV) treatment, with over 95% of patients infected with HCV genotype 1 achieving sustained virological response (SVR). Nevertheless, the majority of patients globally are unable to access these treatments because of cost and infrastructure constraints and, thus, remain untreated and uncured. DATA SOURCE Relevant articles of peginterferon (PegIFN)-based treatments in HCV and sofosbuvir-based treatments, simeprevir, daclatasvir/asunaprevir, ritonavir-boosted paritaprevir/ombitasvir/dasabuvir, and grazoprevir/elbasvir, were searched in PubMed database, including general population and special population. RESULTS PegIFN in combination with ribavirin remains an important and relevant option for some patients, achieving SVR rates of up to 79% in genotype 1 and 89% in genotype 2 or 3 infections, which increases for patients with favorable IL28B genotypes. Triple therapy of DAA plus PegIFN/ribavirin is effective in treating difficult-to-cure patients infected with HCV genotype 3 or with resistance-associated variants. Owing to its long history in HCV management, the efficacy, tolerability and long-term outcomes associated with PegIFN alfa-2a are well established and have been validated in large-scale studies and in clinical practice for many populations. Furthermore, emerging data show that IFN-induced SVR is associated with lower incidences of hepatocellular carcinoma compared with DAAs. On the contrary, novel DAAs have yet to be studied in special populations, and long-term outcomes, particularly tumor development and recurrence in patients with cirrhosis and/or hepatocellular carcinoma, and reactivation of HBV in dually infected patients, are still unclear. CONCLUSION In this interferon-free era, PegIFN-based regimens remain a safe and effective option for selected HCV patients.
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Affiliation(s)
- Yan Huang
- Shanghai Roche Pharmaceuticals Ltd., Shanghai 201203, Beijing, China
| | - Ming-Hui Li
- Liver Disease Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Min Hou
- Shanghai Roche Pharmaceuticals Ltd., Shanghai 201203, Beijing, China
| | - Yao Xie
- Liver Disease Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
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Kesiraju S, Srikanti P, Sahariah S. Hepatitis C infection in renal transplantation: pathogenesis, current impact and emerging trends. Virusdisease 2017; 28:233-241. [PMID: 29291208 DOI: 10.1007/s13337-017-0393-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2017] [Accepted: 08/17/2017] [Indexed: 02/07/2023] Open
Abstract
Prevalence of hepatitis C infection, which is associated with mortality and morbidity, is higher in chronic kidney disease patients on hemodialysis and transplant recipients when compared to non HCV infected patients. In addition to the conventional risk factors, HCV infection maybe an additional risk factor in the development of chronic kidney disease. HCV causes adverse effects leading to the poor long term outcome in renal transplant recipients; hepatitis C infection can cause both hepatic as well as extra hepatic complications. Prior evaluation and management of HCV infection is recommended for better long term outcome as there are chances of higher rejection rates with HCV treatment. However transplantation is not contraindicated in those patients who cannot be treated prior to the transplantation as patient survival is better when compared to dialysis patients. Kidney Disease Outcome Quality Initiative Clinical Practice Guidelines recommend interferon based therapy only when there is a rapid worsening of HCV related hepatic injury in transplant recipients. HCV treatment has been improved by the addition of direct acting antiviral, protease inhibitors and polymerase inhibitors. Combination therapies are showing improved sustained virological response rates. NS3-4A protease inhibitors, nucleotidic/nucleosidic NS5A and NS5B polymerase inhibitors are promising treatments which are under trials with different combinations. The focus of this review is to evaluate and optimize the treatment options of co-existing HCV infection in renal transplant recipients and discuss more promising alternative treatment regimen.
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Affiliation(s)
- Sailaja Kesiraju
- Transimmun- Transplantation Immunology and Research Centre, Somajiguda, Hyderabad, Andhra Pradesh 500082 India.,Department of Immunology, Bhagwan Mahavir Medical Research Centre, Hyderabad, India
| | | | - S Sahariah
- Transimmun- Transplantation Immunology and Research Centre, Somajiguda, Hyderabad, Andhra Pradesh 500082 India.,Department of Nephrology and Transplantation, Krishna Institute of Medical Sciences, Hyderabad, India
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Goel A, Bhadauria DS, Kaul A, Prasad N, Gupta A, Sharma RK, Rai P, Aggarwal R. Safety and effectiveness of response-guided therapy using pegylated interferon and ribavirin for chronic hepatitis C virus infection in patients on maintenance dialysis. Nephrology (Carlton) 2017; 22:706-711. [PMID: 27286895 DOI: 10.1111/nep.12833] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2016] [Revised: 05/18/2016] [Accepted: 06/01/2016] [Indexed: 12/17/2022]
Affiliation(s)
- Amit Goel
- Department of Gastroenterology; Sanjay Gandhi Postgraduate Institute of Medical Sciences; Lucknow India
| | | | - Anupma Kaul
- Department of Nephrology; Sanjay Gandhi Postgraduate Institute of Medical Sciences; Lucknow India
| | - Narayan Prasad
- Department of Nephrology; Sanjay Gandhi Postgraduate Institute of Medical Sciences; Lucknow India
| | - Amit Gupta
- Department of Nephrology; Sanjay Gandhi Postgraduate Institute of Medical Sciences; Lucknow India
| | - Raj Kumar Sharma
- Department of Nephrology; Sanjay Gandhi Postgraduate Institute of Medical Sciences; Lucknow India
| | - Praveer Rai
- Department of Gastroenterology; Sanjay Gandhi Postgraduate Institute of Medical Sciences; Lucknow India
| | - Rakesh Aggarwal
- Department of Gastroenterology; Sanjay Gandhi Postgraduate Institute of Medical Sciences; Lucknow India
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Abad S, Vega A, Rincón D, Hernández E, Mérida E, Macías N, Muñoz R, Milla M, Luño J, López-Gómez JM. Effectiveness of direct-acting antivirals in Hepatitis C virus infection in haemodialysis patients. Nefrologia 2017; 37:158-163. [PMID: 27914803 DOI: 10.1016/j.nefroe.2017.04.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Revised: 09/29/2016] [Accepted: 10/02/2016] [Indexed: 01/03/2025] Open
Abstract
Hepatitis C virus (HCV) infection is highly prevalent among patients on haemodialysis and leads to a poorer prognosis compared to patients who do not have said infection. Treatment with interferon and ribavirin is poorly tolerated and there are limited data on the experience with new direct-acting antivirals (DAAs). The aim of this study is to retrospectively analyse the current prevalence of HCV infection and efficacy and safety results with different DAA regimens in the haemodialysis population of 2hospital areas. This is a multicentre, retrospective and observational study in which HCV antibodies were analysed in 465 patients, with positive antibody findings in 54 of them (11.6%). Among these, 29 cases (53.7%) with genotypes 1 and 4 were treated with different DAA regimens, including combinations of paritaprevir/ritonavir, ombitasvir, dasabuvir, sofosbuvir, simeprevir, daclatasvir and ledipasvir, with/without ribavirin. Mean age was 53.3±7.9 years, 72.4% of patients were male and the most important aetiology of chronic kidney disease involved glomerular abnormalities. In 100% of cases, a sustained viral response was achieved after 24 weeks, regardless of DAA regimen received. Adverse effects were not relevant and no case required stopping treatment. In 15 cases, ribavirin was combined with the DAA. In these cases, the most significant adverse effect was anaemic tendency, which was reflected in the increase of the dose of erythropoietin stimulating agents, although none required transfusions. In summary, we conclude that new DAAs for the treatment of HCV in haemodialysis patients are highly effective with minimal adverse effects; it is a very important advance in HCV management. These patients are therefore expected to have a much better prognosis than they have had until very recently.
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Affiliation(s)
- Soraya Abad
- Servicio de Nefrología, Hospital Universitario Gregorio Marañón, Madrid, España
| | - Almudena Vega
- Servicio de Nefrología, Hospital Universitario Gregorio Marañón, Madrid, España
| | - Diego Rincón
- Servicio de Aparato Digestivo, Hospital Universitario Gregorio Marañón, Madrid, España
| | | | | | - Nicolás Macías
- Servicio de Nefrología, Hospital Universitario Gregorio Marañón, Madrid, España
| | - Raquel Muñoz
- Servicio de Medicina del Aparato Digestivo, Hospital 12 de Octubre, Madrid, España
| | - Mónica Milla
- Servicio de Nefrología. Hospital 12 de Octubre, Madrid, España
| | - Jose Luño
- Servicio de Nefrología, Hospital Universitario Gregorio Marañón, Madrid, España
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Hepatitis C virus infection in maintenance hemodialysis patients: recommendations for diagnostics and treatment. Int J Artif Organs 2017; 39:590-595. [PMID: 28165585 DOI: 10.5301/ijao.5000548] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/31/2016] [Indexed: 12/19/2022]
Abstract
Hepatitis C virus (HCV) infection is highly prevalent among patients treated with maintenance hemodialysis and is an important cause of morbidity and mortality. It is necessary to determine the HCV genotype and the viral load to monitor the clinical and laboratory features and to establish an optimal antiviral treatment strategy. Antiviral treatments are presented with a standard interferon-based regimen and new direct-acting antiviral agents. The advent of direct-acting antivirals has improved the efficacy and safety of HCV treatment for most patients, even in difficult-to-treat populations such as patients on hemodialysis. HCV treatment with direct-acting antivirals in hemodialysis patients is highly effective, with viral eradication rates similar to those seen in patients without chronic kidney disease and with acceptable adverse event profiles.
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30
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Abad S, Vega A, Hernández E, Mérida E, de Sequera P, Albalate M, Macías N, Milla M, López-Gómez JM. Universal Sustained Viral Response to the Combination of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with/without Ribavirin in Patients on Hemodialysis Infected with Hepatitis C Virus Genotypes 1 and 4. Am J Nephrol 2017; 45:267-272. [PMID: 28166520 DOI: 10.1159/000454819] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2016] [Accepted: 11/12/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is highly prevalent among patients on hemodialysis (HD) and is associated with poor prognosis. Treatment with interferon and ribavirin is poorly tolerated, and few data are available on the impact of new direct-acting antivirals (DAAs). This study was intended to analyze the efficacy and safety of treatment with a combination of ombitasvir/paritaprevir/ritonavir and dasabuvir with/without ribavirin in HCV-infected patients on HD from 3 hospitals. METHODS This is a multicentric study. We analyze the clinical course of all patients on HD with HCV infection who had been treated with the combination of ombitasvir/paritaprevir/ritonavir and dasabuvir in 3 hospitals in Madrid, Spain. All patients under treatment had undergone Transient elastography (FibroScan®) and HCV RNA (PCR) and HCV genotype were determined simultaneously. RESULTS Thirty-five patients aged 53.3 ± 8.9 years (68.6% males) and with genotypes 1 and 4 were treated with the DAA regimen, and 17 were also given ribavirin. The most common etiology was glomerular disease. Sustained viral response was achieved in 100% of patients. Adverse effects were negligible, and no patient had to discontinue treatment. The most significant side effect was anemia, which led to a significant increase in the dose of erythropoiesis-stimulating agents. Anemia was more marked in patients receiving ribavirin. No patients required transfusions. CONCLUSION A combination of ombitasvir/paritaprevir/ritonavir and dasabuvir with/without ribavirin for the treatment of HCV in patients on HD is highly effective and causes minimal side effects. This regimen represents a major advance in disease management. A considerable improvement in prognosis seems likely.
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Affiliation(s)
- Soraya Abad
- Service of Nephrology, Hospital Universitario Gregorio Marañón, Madrid, Spain
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31
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Mücke MM, Mücke VT, Lange CM, Zeuzem S. Special populations: treating hepatitis C in patients with decompensated cirrhosis and/or advanced renal impairment. Liver Int 2017; 37 Suppl 1:19-25. [PMID: 28052635 DOI: 10.1111/liv.13279] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Accepted: 10/14/2016] [Indexed: 12/21/2022]
Abstract
Direct-acting antivirals have revolutionized the treatment of hepatitis C. Sustained virological response rates of at least 95% have become common in the general population. However, along with the ageing of the HCV population, physicians face a growing group of HCV-infected patients with advanced liver and/or renal impairment. The safety and efficacy of treatment remains a clinical challenge in these patients. This review focuses on the current state of knowledge and treatment regimens in patients with decompensated cirrhosis and severe renal impairment. It shows that distinct interferon-free treatments can achieve favourable sustained virological response rates in these difficult-to-treat patients. Moreover, pitfalls and special considerations as well as new emerging challenges in an era of interferon-free regimens will be presented in this article.
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Affiliation(s)
- Marcus M Mücke
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt a.M., Germany
| | - Victoria T Mücke
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt a.M., Germany
| | - Christian M Lange
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt a.M., Germany
| | - Stefan Zeuzem
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt a.M., Germany
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32
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Patel YA, Muir AJ. Treatment of HCV in Renal Disease: Subtle Management Considerations in the Era of Direct-acting Antivirals. CURRENT HEPATOLOGY REPORTS 2016; 15:285-290. [PMID: 28584732 DOI: 10.1007/s11901-016-0319-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Chronic hepatitis C virus (HCV) infection is burdensome in patients with chronic kidney disease and contributes to substantial liver-related and all-cause morbidity and mortality. HCV infection itself may cause kidney dysfunction, as exemplified through mixed cryoglobulinemic vasculitis. HCV is more prevalent in patients with significant kidney disease compared to the general population, and recent reports have shown inadvertent HCV transmission in U.S. hemodialysis centers. Further, HCV has been demonstrated to accelerate kidney dysfunction and is associated with worse clinical outcomes in patients with kidney disease. As such, the HCV-infected population with concurrent kidney disease is an important patient subgroup that warrants focused medical care and attention. With the advent of direct-acting antivirals (DAAs), the successful treatment of HCV is now a medical reality for many patients. Nuances in regimen selection and timing need to be considered when treating those with kidney dysfunction, particularly for those considering kidney transplantation.
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Affiliation(s)
- Yuval A Patel
- Division of Gastroenterology, Duke University Medical Center, P.O. Box 3913, Durham, NC, 27710
| | - Andrew J Muir
- Division of Gastroenterology, Duke University Medical Center, P.O. Box 3913, Durham, NC, 27710
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33
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Abad S, Vega A, Rincón D, Hernández E, Mérida E, Macías N, Muñoz R, Milla M, Luño J, López-Gómez JM. Effectiveness of direct-acting antivirals in Hepatitis C virus infection in haemodialysis patients. Nefrologia 2016; 37:158-163. [PMID: 27914803 DOI: 10.1016/j.nefro.2016.10.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Revised: 09/29/2016] [Accepted: 10/02/2016] [Indexed: 02/07/2023] Open
Abstract
Hepatitis C virus (HCV) infection is highly prevalent among patients on haemodialysis and leads to a poorer prognosis compared to patients who do not have said infection. Treatment with interferon and ribavirin is poorly tolerated and there are limited data on the experience with new direct-acting antivirals (DAAs). The aim of this study is to retrospectively analyse the current prevalence of HCV infection and efficacy and safety results with different DAA regimens in the haemodialysis population of 2hospital areas. This is a multicentre, retrospective and observational study in which HCV antibodies were analysed in 465 patients, with positive antibody findings in 54 of them (11.6%). Among these, 29 cases (53.7%) with genotypes 1 and 4 were treated with different DAA regimens, including combinations of paritaprevir/ritonavir, ombitasvir, dasabuvir, sofosbuvir, simeprevir, daclatasvir and ledipasvir, with/without ribavirin. Mean age was 53.3±7.9 years, 72.4% of patients were male and the most important aetiology of chronic kidney disease involved glomerular abnormalities. In 100% of cases, a sustained viral response was achieved after 24 weeks, regardless of DAA regimen received. Adverse effects were not relevant and no case required stopping treatment. In 15 cases, ribavirin was combined with the DAA. In these cases, the most significant adverse effect was anaemic tendency, which was reflected in the increase of the dose of erythropoietin stimulating agents, although none required transfusions. In summary, we conclude that new DAAs for the treatment of HCV in haemodialysis patients are highly effective with minimal adverse effects; it is a very important advance in HCV management. These patients are therefore expected to have a much better prognosis than they have had until very recently.
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Affiliation(s)
- Soraya Abad
- Servicio de Nefrología, Hospital Universitario Gregorio Marañón, Madrid, España
| | - Almudena Vega
- Servicio de Nefrología, Hospital Universitario Gregorio Marañón, Madrid, España
| | - Diego Rincón
- Servicio de Aparato Digestivo, Hospital Universitario Gregorio Marañón, Madrid, España
| | | | | | - Nicolás Macías
- Servicio de Nefrología, Hospital Universitario Gregorio Marañón, Madrid, España
| | - Raquel Muñoz
- Servicio de Medicina del Aparato Digestivo, Hospital 12 de Octubre, Madrid, España
| | - Mónica Milla
- Servicio de Nefrología. Hospital 12 de Octubre, Madrid, España
| | - Jose Luño
- Servicio de Nefrología, Hospital Universitario Gregorio Marañón, Madrid, España
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Rostaing L, Alric L, Kamar N. Use of direct-acting agents for hepatitis C virus-positive kidney transplant candidates and kidney transplant recipients. Transpl Int 2016; 29:1257-1265. [DOI: 10.1111/tri.12870] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Revised: 12/14/2015] [Accepted: 09/30/2016] [Indexed: 12/15/2022]
Affiliation(s)
- Lionel Rostaing
- Department of Nephrology and Organ Transplantation; CHU Rangueil; Toulouse France
- INSERM U563, IFR-BMT; CHU Purpan; Toulouse France
- Université Paul Sabatier; Toulouse France
| | - Laurent Alric
- Department of Internal Medicine and Digestive Diseases; CHU Purpan; Toulouse France
- UMR 152, IRD; Toulouse 3 University; Toulouse France
| | - Nassim Kamar
- Université Paul Sabatier; Toulouse France
- INSERM U858; CHU Rangueil & Purpan; Toulouse France
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Akhan S, Sayan M, Sargin Altunok E, Aynioglu A. A case report: antiviral triple therapy with telaprevir in a haemodialysed HCV patient in Turkey. Acta Clin Belg 2016. [DOI: 10.1179/2295333715y.0000000046] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
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Cacoub P, Desbois AC, Isnard-Bagnis C, Rocatello D, Ferri C. Hepatitis C virus infection and chronic kidney disease: Time for reappraisal. J Hepatol 2016; 65:S82-S94. [PMID: 27641990 DOI: 10.1016/j.jhep.2016.06.011] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2016] [Revised: 06/06/2016] [Accepted: 06/07/2016] [Indexed: 12/18/2022]
Abstract
Hepatitis C virus (HCV) infection is associated with tremendous morbidity and mortality due to liver complications. HCV infection is also associated with many extrahepatic manifestations including cardiovascular diseases, glucose metabolism impairment, cryoglobulinemia vasculitis, B cell non-Hodgkin lymphoma and chronic kidney disease (CKD). Many studies have shown a strong association between HCV and CKD, by reporting (i) an increased prevalence of HCV infection in patients on haemodialysis, (ii) an increased incidence of CKD and proteinuria in HCV-infected patients, and (iii) the development of membranoproliferative glomerulonephritis secondary to HCV-induced cryoglobulinemia vasculitis. HCV seropositivity is found to be associated with an increased relative risk for all-cause and cardiovascular mortality in the dialysis population. HCV seropositivity is linked to lower patient and graft survival after kidney transplantation. Such poor HCV-associated prognosis should have encouraged clinicians to treat HCV in CKD patients. However, due to frequent side effects and the poor efficacy of interferon-based treatments, very few HCV dialysis patients have received HCV medications until now. The emergence of new direct acting, interferon-free antiviral treatment, leading to HCV cure in most cases with a satisfactory safety profile, will shortly modify the management of HCV infection in CKD patients. In patients with a glomerular filtration rate (GFR) >30ml/min, the choice of DAA is not restricted. In those with a GFR <30 and >15ml/min, only paritaprevir/ritonavir/ombitasvir/dasabuvir or a grazoprevir plus elbasvir regimen are approved. In patients with end stage renal disease (GFR <15ml/min or dialysis), current data only allows for the use of a grazoprevir plus elbasvir combination. No doubt these data will be modified in the future with the advent of new studies including larger cohorts of HCV patients with renal impairment.
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Affiliation(s)
- Patrice Cacoub
- Sorbonne Universités, UPMC Université Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), F-75005 Paris, France; INSERM, UMR_S 959, F-75013 Paris, France; CNRS, FRE3632, F-75005 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, F-75013 Paris, France.
| | - Anne Claire Desbois
- Sorbonne Universités, UPMC Université Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), F-75005 Paris, France; INSERM, UMR_S 959, F-75013 Paris, France; CNRS, FRE3632, F-75005 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, F-75013 Paris, France
| | - Corinne Isnard-Bagnis
- Sorbonne Universités, UPMC Université Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), F-75005 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Nephrology, F-75013 Paris, France
| | - Dario Rocatello
- Center of Research of Immunopathology and Rare Diseases, and Nephrology and Dialysis Unit. San G. Bosco Hospital and University of Turin, Italy
| | - Clodoveo Ferri
- Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, 41124 Modena, Italy
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Sundaram V, Kowdley KV. Dual daclatasvir and sofosbuvir for treatment of genotype 3 chronic hepatitis C virus infection. Expert Rev Gastroenterol Hepatol 2016; 10:13-20. [PMID: 26560449 DOI: 10.1586/17474124.2016.1116937] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Chronic hepatitis C virus (HCV) infection is one of the most common etiologies of liver-related mortality throughout the world. Traditionally, therapy has been focused on pegylated interferon in combination with ribavirin, with clinical trials demonstrating that HCV genotype 1 had the lowest response rate (40-50%), while genotype 3 had an intermediate response rate (60-70%). Recently, significant advances have been made with all-oral direct-acting antiviral (DAA) therapy, which have significantly improved cure rates for HCV genotype 1. Accordingly, HCV genotype 3 is now potentially the most difficult to treat. One of the most potent DAA medications is sofosbuvir, a pan-genotypic nucleotide analogue that inhibits the NS5B polymerase of HCV. Daclatasvir, a pan-genotypic inhibitor of the HCV NS5A replication complex, was recently approved in the United States for treatment of HCV genotype 3 in conjunction with sofosbuvir. This combination may provide a powerful tool in the treatment of HCV genotype 3.
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Affiliation(s)
- Vinay Sundaram
- a Department of Medicine and Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , CA , USA
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Mogahed EA, Abdelaziz H, Helmy H, Ghita H, Abdel Mawla MA, Hassanin F, Fadel FI, El-Karaksy H. Safety and Efficacy of Pegylated Interferon Alpha-2b Monotherapy in Hepatitis C Virus-Infected Children with End-Stage Renal Disease on Hemodialysis. J Interferon Cytokine Res 2016; 36:681-688. [PMID: 27656950 DOI: 10.1089/jir.2016.0019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Treatment of hepatitis C virus (HCV) in end-stage renal disease (ESRD) patients is an important issue before kidney transplantation (KT). The aim of the study is to assess the efficacy and tolerability of HCV treatment with pegylated interferon (PEG IFN)-α 2b in children with ESRD. The study included 17 children, aged 3-18 years with ESRD on hemodialysis (HD), with chronic HCV. They received 40 μg/m2 of PEG IFN-α 2b once-weekly subcutaneous injections for 48 weeks. Early virological response (EVR) was achieved in 76.5%. At week 24, 8 patients had negative HCV RNA. Six patients received KT during therapy. Treatment was discontinued in 2 patients: one for anemia and another for retinopathy. Two patients completed 48 weeks of therapy and both achieved end-of-treatment response and sustained virological response (SVR). Constitutional symptoms were the most frequently reported side effects. Neutropenia occurred in 10 patients (58.8%), drop in hemoglobin in 10, and thrombocytopenia in 9. HCV-infected children with ESRD on HD have high EVR (76.5%) on IFN monotherapy. SVR could not be assessed due to the high dropout rate related mainly to early transplantation. Constitutional symptoms and hematological side effects were the most frequently reported side effects.
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Affiliation(s)
- Engy A Mogahed
- 1 Department of Pediatrics, Kasr Alainy Medical School, Cairo University , Cairo, Egypt
| | - Hanan Abdelaziz
- 1 Department of Pediatrics, Kasr Alainy Medical School, Cairo University , Cairo, Egypt
| | - Heba Helmy
- 1 Department of Pediatrics, Kasr Alainy Medical School, Cairo University , Cairo, Egypt
| | - Haytham Ghita
- 1 Department of Pediatrics, Kasr Alainy Medical School, Cairo University , Cairo, Egypt
| | | | - Fetouh Hassanin
- 3 Faculty of Pharmacy, Misr International University , Cairo, Egypt
| | - Fatina I Fadel
- 1 Department of Pediatrics, Kasr Alainy Medical School, Cairo University , Cairo, Egypt
| | - Hanaa El-Karaksy
- 1 Department of Pediatrics, Kasr Alainy Medical School, Cairo University , Cairo, Egypt
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Agarwal SK, Bhowmik D, Mahajan S, Bagchi S. Pegylated interferon monotherapy for hepatitis C virus infection in patients on hemodialysis: A single center study. Indian J Nephrol 2016; 26:244-51. [PMID: 27512295 PMCID: PMC4964683 DOI: 10.4103/0971-4065.172228] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
There is no published study from India on hepatitis C virus (HCV) treatment in dialysis patients. Patients on dialysis with HCV infection treated with pegylated interferon (Peg-INF) monotherapy were studied. All patients were subjected to HCV-polymerase chain reaction, viral load, genotype, and liver biopsy. Quantitative HCV-RNA was performed monthly. Patients with genotype 1 and 4 were given 12 month therapy while those with genotypes 2 and 3 were given 6 months therapy. Response was classified as per standard criteria of rapid virological response (RVR), early virological response (EVR), end of treatment response (ETR), and sustained virological response (SVR). A total of 85 patients were treated. Mean age was 35.2 ± 10.5 (range 15-67) years, and 77.6% were males. HCV genotypes were 1 in 40.9%, 2 in 12%, 3 in 36.1%, 4 in 3.6%, and others in 7.2%. Mean viral load was 10(6) copies/mL. Mean liver biopsy grade was 4 ± 1.7 and stage 0.8 ± 0.8. Mean time from diagnosis of HCV infection and the treatment start was 10.7 ± 14.3 months. One patient died of unrelated illness, one was lost to follow-up, and three could not sustain treatment due to cost. Forty-three of the 80 (54%) patients had RVR while 49 (61%) patients had EVR and ETR. There was no difference in term of RVR related to genotype. Fifty -four percentage had SVR. Mild flu-like symptoms were seen in all patients. Sixty-four (80%) patients required increase in erythropoietin doses. Twenty-eight (35%) patients developed leukopenia (three treatment-limiting) and 16 (20%) developed thrombocytopenia (one treatment-limiting). Five patients developed tuberculosis, five bacterial pneumonia, and one bacterial knee monoarthritis. None of the patients developed depression. Our study concludes that Peg-INF monotherapy resulted in 54% RVR and SVR in dialysis patients with HCV infection. Therapy was well-tolerated with minimal side effects. There was no effect of viral genotype on response to therapy.
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Affiliation(s)
- S K Agarwal
- Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
| | - D Bhowmik
- Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
| | - S Mahajan
- Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
| | - S Bagchi
- Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
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Safety and efficacy of dual direct-acting antiviral therapy (daclatasvir and asunaprevir) for chronic hepatitis C virus genotype 1 infection in patients on hemodialysis. J Gastroenterol 2016; 51:741-7. [PMID: 26872889 DOI: 10.1007/s00535-016-1174-4] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Accepted: 01/18/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a major comorbidity in patients receiving hemodialysis. Interferon-based antiviral therapy to eradicate HCV is less effective in patients receiving hemodialysis than patients without renal dysfunction. Recently reported combination therapy with two oral direct-acting antiviral drugs, daclatasvir and asunaprevir, both of which are metabolized in the liver and excreted into the bile ducts, reportedly showed a high rate of HCV eradication. We evaluated the safety and efficacy of this therapy in patients receiving hemodialysis. METHODS The safety and viral responses were compared among patients infected with HCV genotype 1, between 28 patients receiving hemodialysis, and propensity score-matched 56 patients without renal dysfunction. RESULTS The reduction in serum HCV RNA levels 1 day after the start of therapy was significantly larger (p = 0.0329) and the disappearance of serum HCV RNA occurred significantly earlier (p = 0.0017) in patients receiving hemodialysis than those without renal dysfunction. The rates of sustained virologic response, i.e., the eradication of HCV, were comparable between two groups; the rate of SVR12 was 100 % in patients receiving hemodialysis and 94.6 % in patients without renal dysfunction. No adverse constitutional events were observed in either of the groups. The elevation of serum alanine aminotransferase levels, a known adverse effect of these drugs, was observed in comparable rate of patients between the two groups. CONCLUSIONS The therapy with daclatasvir and asunaprevir has high antiviral efficacy in patients receiving hemodialysis with a comparable safety profile to patients without renal dysfunction.
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Evaluation of the Pharmacokinetics and Renal Excretion of Simeprevir in Subjects with Renal Impairment. Drugs R D 2016; 15:261-70. [PMID: 26248593 PMCID: PMC4561054 DOI: 10.1007/s40268-015-0101-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Simeprevir is a N3/4 protease inhibitor approved for the treatment of hepatitis C virus (HCV) infection. HCV prevalence is higher in patients with chronic kidney disease compared with the general population; safe and efficacious therapies in renal impairment are needed. OBJECTIVES To evaluate simeprevir renal excretion in healthy subjects and to compare the simeprevir steady-state pharmacokinetics between subjects with severe renal impairment and healthy subjects. METHODS In the mass balance study, healthy adults received a single 200-mg dose of (14)C-simeprevir; radioactivity in the urine and feces was quantified until concentrations were <2% of the administered dose and seven or more stools were produced. In the pharmacokinetic study, non-HCV-infected adults with severe renal impairment (estimated glomerular filtration rate ≤29 mL/min/1.73 m(2)) and matched healthy subjects (estimated glomerular filtration rate ≥80 mL/min/1.73 m(2)) received 150 mg simeprevir for 7 days. Pharmacokinetic analysis was performed post-dose on Day 7. RESULTS (14)C-simeprevir recovery from the urine was low (0.009-0.138% of total dose). The minimum plasma concentration, maximum plasma concentration, and area under the plasma concentration-time curve at 24 h were 71, 34, and 62% higher, respectively, in subjects with severe renal impairment compared with healthy subjects. The mean fraction of simeprevir unbound to protein was <0.0001 (all subjects). Most adverse events were grade I or II; one subject with renal impairment who was receiving fenofibrate presented with grade 3 rhabdomyolysis. CONCLUSIONS Simeprevir plasma concentrations were mildly elevated in subjects with severe renal impairment. The results suggest that simeprevir may be administered without dose adjustment in patients with renal impairment.
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Nazario HE, Ndungu M, Modi AA. Sofosbuvir and simeprevir in hepatitis C genotype 1-patients with end-stage renal disease on haemodialysis or GFR <30 ml/min. Liver Int 2016; 36:798-801. [PMID: 26583882 DOI: 10.1111/liv.13025] [Citation(s) in RCA: 93] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2015] [Accepted: 11/06/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND & AIMS Treating chronic hepatitis C (CHC) in patients with end-stage renal disease (ESRD) has suboptimal tolerability and cure rates. Safety and efficacy of sofosbuvir plus simeprevir regimen in CHC-infected patients with ESRD on haemodialysis (HD) or glomerular filtration rate (GFR) <30 ml/min is unknown. We evaluated the safety and efficacy of sofosbuvir and simeprevir in this special patient population. METHODS All (n = 17) patients in the analysis had ESRD on HD or GFR <30 ml/min. All received sofosbuvir 400 mg daily and simeprevir 150 mg daily, without ribavirin for 12 weeks. Safety and efficacy data were collected; including SVR4 and SVR12 data for all patients after completing therapy. RESULTS In this 17 patient cohort, eight (47%) were cirrhotic, four (24%) had stage three liver fibrosis and 13 (76%) were genotype 1A. All 17 have completed 12 weeks of therapy. Treatment was overall well tolerated with no treatment discontinuations reported. Four (24%) patients reported mild adverse events (AE). These AEs were insomnia (n = 2), headache (n = 1), nausea (n = 1) and worsening anaemia requiring blood transfusion (n = 1). All 17 patients reached post-treatment week-12 follow-up, and achieved SVR12 or virological cure (100% SVR12). CONCLUSIONS Daily, full dose of sofosbuvir plus simeprevir for 12 weeks of therapy appears to be well tolerated in patients with ESRD on HD or GFR <30 ml/min. Most common AEs resembled those of healthier CHC patients without significant renal impairment. The cure rates obtained in this cohort treated with sofosbuvir and simeprevir are dramatically superior to any previous treatment regimen studied & published in this special patient population.
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Affiliation(s)
- Hector E Nazario
- Division of Hepatology, The Liver Institute at Methodist Dallas Medical Center, Dallas, TX, USA
| | - Milka Ndungu
- Division of Hepatology, The Liver Institute at Methodist Dallas Medical Center, Dallas, TX, USA
| | - Apurva A Modi
- Division of Hepatology, Liver Consultants of Texas, Baylor All Saints Medical Center, Fort Worth, TX, USA
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Singh T, Guirguis J, Anthony S, Rivas J, Hanouneh IA, Alkhouri N. Sofosbuvir-based treatment is safe and effective in patients with chronic hepatitis C infection and end stage renal disease: a case series. Liver Int 2016; 36:802-6. [PMID: 26824848 DOI: 10.1111/liv.13078] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2015] [Accepted: 01/20/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Interferon and ribavirin-free regimens to treat chronic hepatitis C virus (HCV) infection in patients with end stage renal disease are not approved and represent an area of unmet clinical need. We report our experience on the safety and efficacy of sofosbuvir/simeprevir and sofosbuvir/ledipasvir therapy in patients on haemodialysis. METHODS Patients with chronic HCV infection on haemodialysis were included in this study. Patients were started on either sofosbuvir/simeprevir or sofosbuvir/ledipasvir. Routine clinical and laboratory data were collected at baseline and during treatment. The primary outcome was sustained virological response at week 12 (SVR12). RESULTS Eight patients with mean age 56.8 ± 20 years were included in this study. Seven were treatment naïve and one was a priori null responder to interferon-based therapy. Four patients were started on sofosbuvir/simeprevir and four on sofosbuvir/ledipasvir for 12 weeks. Therapy was well tolerated overall with nausea/vomiting, pruritus, headache and a 2 g/dl drop in haemoglobin developing in one patient each. No patient discontinued therapy because of side effects. Comparison of labs at baseline and nadir levels during treatment revealed no significant change in haemoglobin (10.8 ± 2.4 g/dl vs 10.3 ± 1.6 g/dl), platelet count (198 ± 164 k/μl vs 184.5 ± 162/μl) and bilirubin (0.3 ± 0.4 mg/dl vs 0.25 ± 0.15 mg/dl). Eight of eight patients had undetectable HCV RNA at the end of treatment. One patient was lost to follow up and the remaining seven achieved SVR12. CONCLUSION Full dose sofosbuvir/simeprevir or sofosbuvir/ledipasvir therapy for HCV-infected patients with end stage renal disease was well tolerated with no discontinuation owing to side effects and no significant adverse events.
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Affiliation(s)
- Tavankit Singh
- Department of Internal Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - John Guirguis
- Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Sumi Anthony
- Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
| | - John Rivas
- Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
| | | | - Naim Alkhouri
- Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA.,Department of Pediatric Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
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Fabrizi F, Martin P, Messa P. New treatment for hepatitis C in chronic kidney disease, dialysis, and transplant. Kidney Int 2016; 89:988-994. [PMID: 27083277 DOI: 10.1016/j.kint.2016.01.011] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2015] [Revised: 01/05/2016] [Accepted: 01/27/2016] [Indexed: 12/16/2022]
Abstract
The evidence that chronic hepatitis C plays a detrimental role in survival among patients on maintenance dialysis or renal transplant recipients promotes the antiviral treatment of hepatitis C virus (HCV) among chronic kidney disease patients. Also, it seems that HCV infection is associated with an increased risk of developing chronic kidney disease in the adult general population. Interferon-based regimens have provided limited efficacy and safety among chronic kidney disease patients, whereas the advent of the new direct-acting antivirals for the treatment of hepatitis C (launched over the past 5 years) has given the opportunity to reach sustained virologic response rates of 90% for many patient groups. Unfortunately, poor information exists regarding the antiviral treatment of hepatitis C in the chronic kidney disease population. The first published data on the treatment of hepatitis C among patients with chronic kidney disease (stage 4-5) and HCV genotype 1 regard the grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor) combination; excellent efficacy (sustained viral response, 94.3%; 115/122) and safety have been achieved. Preliminary evidence on the combined treatment of sofosbuvir (NS5B inhibitor) and simeprevir (NS3/4A inhibitor) has given a viral response of 89%, but the size of the study group (n = 38 patients with end-stage renal disease) was small. Some phase 2 and 3 clinical trials based on other antiviral combinations (3D regimen, sofosbuvir/ledipasvir, or other sofosbuvir-containing approaches) are ongoing. Thus, the antiviral regimens based on direct-acting antivirals promise to play a pivotal role in the eradication of hepatitis C among kidney disease patients. Direct-acting antivirals are very expensive; in an era of cost containment this is a crucial point either in developed and developing countries. Adverse drug reactions resulting from concomitantly administered medications are another ongoing concern for patients undergoing HCV treatment, particularly for chronic kidney disease patients who have a heavy burden of comorbidities.
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Affiliation(s)
- Fabrizio Fabrizi
- Division of Nephrology and Dialysis, Maggiore Hospital and IRCCS Foundation, Milano, Italy; Division of Hepatology, School of Medicine, University of Miami, Miami, Florida, USA.
| | - Paul Martin
- Division of Hepatology, School of Medicine, University of Miami, Miami, Florida, USA
| | - Piergiorgio Messa
- Division of Nephrology and Dialysis, Maggiore Hospital and IRCCS Foundation, Milano, Italy
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Abstract
The management of hepatitis C virus (HCV) infection in special populations is challenging. The efficacy and safety data of the currently approved all-oral direct-acting antiviral combinations, including sofosbuvir, ledipasvir, daclatasvir, paritaprevir/ritonavir/ombitasvir plus dasabuvir (3D), and ribavirin, is compelling for use in special HCV populations, as has recently been recommended by expert guidelines. The treatment regimens and sustained virological response rates for special populations are nearly similar to those of the general HCV population. Sofosbuvir is not recommended in patients with severe renal impairment, and simeprevir and 3D regimen are not recommended for those with decompensated liver disease.
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Roth D, Nelson DR, Bruchfeld A, Liapakis A, Silva M, Monsour H, Martin P, Pol S, Londoño MC, Hassanein T, Zamor PJ, Zuckerman E, Wan S, Jackson B, Nguyen BY, Robertson M, Barr E, Wahl J, Greaves W. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet 2015; 386:1537-45. [PMID: 26456905 DOI: 10.1016/s0140-6736(15)00349-9] [Citation(s) in RCA: 523] [Impact Index Per Article: 52.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Chronic hepatitis C virus (HCV) infection in patients with stage 4-5 chronic kidney disease increases the risk of death and renal graft failure, yet patients with hepatitis C and chronic kidney disease have few treatment options. This study assesses an all-oral, ribavirin-free regimen in patients with HCV genotype 1 infection and stage 4-5 chronic kidney disease. METHODS In this phase 3 randomised study of safety and observational study of efficacy, patients with HCV genotype 1 infection and chronic kidney disease (stage 4-5 with or without haemodialysis dependence) were randomly assigned to receive grazoprevir (100 mg, NS3/4A protease inhibitor) and elbasvir (50 mg, NS5A inhibitor; immediate treatment group) or placebo (deferred treatment group) once daily for 12 weeks. Randomisation was done centrally with an interactive voice response system. An additional cohort of patients who were not randomised received the same regimen open-label and underwent intensive pharmacokinetic sampling. The primary efficacy outcome was a non-randomised comparison of sustained virological response at 12 weeks (SVR12) after the end of therapy for the combined immediate treatment group and the pharmacokinetic population with a historical control. The primary safety outcome was a randomised comparison between the immediate treatment group and the deferred treatment group. After 4 weeks of follow-up (study week 16), unmasking occurred and patients in the deferred treatment group received grazoprevir and elbasvir. The primary efficacy hypothesis was tested at a two-sided significance level (type I error) of 0·05 using an exact test for a binomial proportion. Safety event rates were compared between immediate treatment and deferred treatment groups using the stratified Miettinen and Nurminen method with baseline dialysis status as the strata. The study is registered at ClinicalTrials.gov, number NCT02092350. FINDINGS 224 patients were randomly assigned to the immediate treatment group with grazoprevir and elbasvir (n=111) or the deferred treatment group (n=113), and 11 were assigned to the intensive pharmacokinetic population. Overall, 179 (76%) were haemodialysis-dependent, 122 (52%) had HCV genotype 1a infection, 189 (80%) were HCV treatment-naive, 14 (6%) were cirrhotic, and 108 (46%) were African American. Of the 122 patients receiving grazoprevir and elbasvir, six were excluded from the primary efficacy analysis for non-virological reasons (death, lost-to-follow-up [n=2], non-compliance, patient withdrawal, and withdrawal by physician for violent behaviour). No patients in the combined immediate treatment group and intensive pharmacokinetic population and five (4%) in the deferred treatment group discontinued because of an adverse event. Most common adverse events were headache, nausea, and fatigue, occurring at similar frequencies in patients receiving active and placebo drugs. SVR12 in the combined immediate treatment group and intensive pharmacokinetic population was 99% (95% CI 95·3-100·0; 115/116), with one relapse 12 weeks after end of treatment when compared with a historical control of 45%, based on meta-analyses of interferon-based regimens used in clinical trials of patients infected with HCV who are on haemodialysis. INTERPRETATION Once-daily grazoprevir and elbasvir for 12 weeks had a low rate of adverse events and was effective in patients infected with HCV genotype 1 and stage 4-5 chronic kidney disease. FUNDING Merck Sharp & Dohme Corp.
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Affiliation(s)
- David Roth
- Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, FL, USA.
| | - David R Nelson
- Clinical and Translational Science Institute, University of Florida, Gainesville, FL, USA
| | - Annette Bruchfeld
- Department of Renal Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden
| | - AnnMarie Liapakis
- Yale University Digestive Disease, Yale New Haven Hospital Transplant Center, New Haven, CT, USA
| | | | - Howard Monsour
- Hepatology & Transplant Medicine, Houston Methodist Hospital, Houston, TX, USA
| | - Paul Martin
- Division of Hepatology, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Stanislas Pol
- Unité d'Hépatologie, Hôpital Cochin; Université Paris Descartes; and UMS20, Institut Pasteur; Paris, France
| | | | | | - Philippe J Zamor
- Division of Hepatology, Carolinas Medical Center, Charlotte, NC, USA
| | - Eli Zuckerman
- Liver Unit, Carmel Medical Center Technion Faculty of Medicine, Haifa, Israel
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Fabrizi F, Messa P. Therapy of hepatitis C by direct-acting anti-virals: the end of HCV in dialysis population? Expert Rev Clin Pharmacol 2015; 8:785-93. [PMID: 26365524 DOI: 10.1586/17512433.2015.1086266] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
The advent of direct-acting anti-viral (DAA) drugs is dramatically changing the treatment of hepatitis C virus (HCV) in patients with intact kidney function ('cure rates' >90% and infrequent adverse events). The information on efficacy and safety of DAAs for HCV therapy in patients with renal failure is limited. We have reviewed the available evidence regarding efficacy and safety of numerous DAAs (boceprevir, telaprevir, sofosbuvir, simeprevir, grazoprevir, elbasvir, ombitasvir, paritaprevir, ritonavir, dasabuvir, ledispavir, daclatasvir, asunaprevir, beclabuvir) in treating HCV-infected patients with renal impairment and/or end-stage renal disease. The major limitation of this review is the paucity of published data and its reliance on abstracts and product monographs. Preliminary data suggest that combination antiviral therapy (grazoprevir and elbasvir) is provided with great efficacy in patients with HCV genotype 1 and chronic kidney disease stage 4 or 5 including those on intermittent dialysis, SVR12, 99% (114/115), according to a per-protocol analysis. In another trial, patients with HCV genotype 1 and chronic kidney disease stage 4 or 5 were given the 3D regimen; an interim evaluation reported that all patients completing treatment to date had viral response (100%, 14/14) but data on sustained viral response are under evaluation. Treatments were generally well tolerated.
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Affiliation(s)
| | - Piergiorgio Messa
- a Division of Nephrology, Maggiore Hospital, IRCCS Foundation , Milano, Italy
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Prabhu RA, Nair S, Pai G, Reddy NP, Suvarna D. Interventions for dialysis patients with hepatitis C virus (HCV) infection. Cochrane Database Syst Rev 2015; 2015:CD007003. [PMID: 26287983 PMCID: PMC9208657 DOI: 10.1002/14651858.cd007003.pub2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is common in chronic kidney disease (CKD) patients on dialysis, causes chronic liver disease, increases mortality and impacts kidney transplant outcomes. Sustained response to the preferred treatment with standard or pegylated (PEG) interferon is seen in 39% with side effects necessitating treatment discontinuation in 20%. We collated evidence for treatment response and harms of interventions for HCV infection in dialysis. OBJECTIVES We aimed to look at the benefits and harms of various interventions for HCV infection in CKD patients on HD or peritoneal dialysis, specifically on mortality, disease relapse, response to treatment, treatment discontinuation, time to recovery, quality of life, cost effectiveness,adverse effects, and other outcomes. We aimed to study comparisons of available interventions with a placebo or control group, combinations of interventions with placebo or control group, interventions with each other singly and in combination, available standard interventions with newer treatment modalities. SEARCH METHODS We searched Cochrane Kidney and Transplant's Specialised Register to 24 March 2015 through contact with the Trials' Search Co-ordinator. We also checked references of reviews, studies and contacted study authors to identify additional studies. SELECTION CRITERIA Randomised controlled trials (RCTs), quasi-RCTs, first period of randomised cross-over studies on interventions for HCV in CKD on dialysis were considered. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by the Cochrane Collaboration and also collected adverse effects data listed in included RCTs. MAIN RESULTS Ten RCTs (361 participants) met our inclusion criteria. Five RCTs (152 participants, 134 analysed) with low to moderate quality of evidence compared standard recombinant interferon with placebo or control. There was no significant difference for mortality (5 studies (134 participants): RR 0.89, 95% CI 0.06 to 13.23), relapses (1 study (36 participants): RR 0.72, 95% CI 0.28 to 1.88), sustained virological response (4 studies (98 participants): RR 3.25, 95% CI 0.81 to 13.07), treatment discontinuation (4 studies (116 participants): RR 4.59, 95% CI 0.49 to 42.69) and number with adverse events (5 studies (143 participants): RR 3.56, 95% CI 0.98 to 13.01). End of treatment response was significantly more for standard interferon (5 studies (132 participants): RR 8.62, 95% CI 3.03 to 24.55). There was overall low to unclear risk of bias and no significant heterogeneity.One RCT (50 participants) with moderate quality of evidence compared PEG interferon and standard interferon. There was no significant difference in mortality (RR 0.33, 95% CI 0.01 to 7.81), relapses (RR 0.72, 95% CI 0.41 to 1.25), sustained virological response (RR 2.40, 95% CI 0.99 to 5.81), treatment discontinuation (RR 0.11, 95% CI 0.01 to 1.96) and number with major adverse events (RR 0.11, 95% CI 0.01 to 1.96). End of treatment response was significantly more for PEG interferon (RR 1.53, 95% CI 1.09 to 2.15). There was overall low risk of bias.Two RCTs (97 participants) with moderate quality of evidence compared two doses of two different preparations of PEG interferon. Subgroup analysis comparing high and low doses of PEG interferon alpha-2a (135 µg/week versus 90 µg/week) and PEG interferon alpha-2b (1 µg/kg versus 0.5 µg/kg body weight/week) found no significant difference in mortality (2 studies (97 participants): RR 4.30, 95% CI 0.76 to 24.33), relapses (1 study (81 participants): RR 1.11, 95% CI 0.45 to 2.77), end of treatment response (2 studies (97 participants): RR 1.42, 95% CI 0.51 to 3.90), sustained virological response (2 studies (97 participants): RR 1.19, 95% CI 0.68 to 2.07), treatment discontinuation (2 studies (97 participants): RR 1.20, 95% CI 0.63 to 2.28), patients with adverse events (2 studies (97 participants): RR 1.05, 95% CI 0.61 to 1.83) or serious adverse events (2 studies (97 participants): RR 1.24, 95% CI 0.72 to 2.14). Both had overall low risk of bias and no significant subgroup differences.Two RCTs (62 participants) with moderate quality of evidence compared standard or PEG interferon alone or in combination with ribavirin. The only reported outcome in both was treatment discontinuation which was significantly more with ribavirin in the one study (RR 0.34, 95% CI 0.14 to 0.84) and pooled 7/10 in the second.No RCTs had data on time to recovery, cost-effectiveness, quality of life, and other outcomes and in peritoneal dialysis. AUTHORS' CONCLUSIONS Our review demonstrated that in CKD patients on haemodialysis with HCV infection treatment with standard interferon brings about an end of treatment but not a sustained virological response and is relatively well tolerated. PEG interferon is more effective than standard interferon for end of treatment response but not for sustained response; both were equally tolerated. Increasing doses of PEG interferon did not improve responses but high and low doses are equally tolerated. Addition of ribavirin results in more treatment discontinuation.
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Affiliation(s)
- Ravindra A Prabhu
- Kasturba Medical College and Hospital Manipal, Manipal UniversityDepartment of NephrologyPO Box 7 Madhav NagarManipalKarnatakaIndia576104
| | - Sreekumar Nair
- Manipal UniversityDepartment of Statistics6th Floor, Health Sciences Library BuildingMadhav NagarManipalKarnatakaIndia576 104
| | - Ganesh Pai
- Kasturba Medical College, Manipal UniversityDepartment of GastroenterologyMadhav NagarManipalKarnatakaIndia576104
| | - Nageswara P Reddy
- Kasturba Medical College, Manipal UniversityDepartment of NephrologyMadhavnagar StreetManipalKarnatakaIndia576104
| | - Deepak Suvarna
- Kasturba Medical College, Manipal UniversityDepartment of GastroenterologyMadhav NagarManipalKarnatakaIndia576104
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Hundemer GL, Sise ME, Wisocky J, Ufere N, Friedman LS, Corey KE, Chung RT. Use of sofosbuvir-based direct-acting antiviral therapy for hepatitis C viral infection in patients with severe renal insufficiency. Infect Dis (Lond) 2015; 47:924-9. [PMID: 26365684 PMCID: PMC4732277 DOI: 10.3109/23744235.2015.1078908] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Sofosbuvir-based direct-acting antiviral therapy revolutionized the treatment of hepatitis C virus (HCV) infection. However, sofosbuvir use is not approved for patients with severe renal insufficiency (estimated glomerular filtration (eGFR) rate below 30 ml/min) or end-stage renal disease (ESRD) based on concerns raised during premarket animal testing over hepatobiliary and cardiovascular toxicity in this population. We report the first published data on use of sofosbuvir-based regimens in patients with severe renal insufficiency and ESRD, focusing on clinical efficacy and safety. Six patients were treated with full dose sofosbuvir; three received sofosbuvir and simeprevir, two received sofosbuvir and ribavirin, and one received sofosbuvir, ribavirin, and interferon. Three of the patients had cirrhosis. On-treatment viral suppression was 100% and sustained virological response (SVR) rate at 12 weeks was 67%. One patient had to discontinue antiviral therapy early due to side effects. No hepatobiliary or cardiovascular toxicity was reported.
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Affiliation(s)
- Gregory L. Hundemer
- Department of Medicine, Massachusetts General Hospital
- Department of Medicine, Harvard Medical School
| | - Meghan E. Sise
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital
- Department of Medicine, Harvard Medical School
| | - Jessica Wisocky
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital
- Department of Medicine, Harvard Medical School
| | - Nneka Ufere
- Department of Medicine, Massachusetts General Hospital
- Department of Medicine, Harvard Medical School
| | - Lawrence S. Friedman
- Department of Medicine, Newton-Wellesley Hospital
- Department of Medicine, Harvard Medical School
- Department of Medicine, Tufts University School of Medicine
| | - Kathleen E. Corey
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital
- Department of Medicine, Harvard Medical School
| | - Raymond T. Chung
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital
- Department of Medicine, Harvard Medical School
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50
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Dzekova-Vidimliski P, Nikolov IG, Matevska-Geshkovska N, Mena S, Rostaing L, Dimovski A, Sikole A. Single nucleotide polymorphisms near IL28B gene and response to treatment of chronic hepatitis C in hemodialysis patients. Ren Fail 2015; 37:1180-4. [PMID: 26156685 DOI: 10.3109/0886022x.2015.1061872] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND It has been shown that single nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) gene were associated with sustained virological response following standard antivirological treatment of chronic hepatitis C. OBJECTIVES The aim of the study was to evaluate the association between SNPs near the IL28B gene and response to the treatment of chronic hepatitis C in hemodialysis patients. PATIENTS AND METHODS The study group included 24 hemodialysis patients with chronic hepatitis C routinely treated with pegylated interferon α-2 a. HCV genotype 1 was the cause of chronic hepatitis C in all study participants. Sustained virological response was determined by an assay with a sensitivity of 20 IU/mL, 6 months after completion of the antivirological treatment. The genotyping of the three most widely studied IL28B gene polymorphisms (rs12979860, rs8099917, and rs12980275) was performed in all study participants. RESULTS Sustained virological response was achieved in 50% of the treated patients. The treatment response was significantly associated with the CC genotype of rs12979860, TT genotype of rs8099917, and AA genotype of rs12980275 (p = 0.003, p = 0.009, and p = 0.012, respectively). CONCLUSIONS The three most widely studied SNPs near the IL28B gene were associated with sustained virological response following antivirological treatment of chronic hepatitis C in hemodialysis patients.
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Affiliation(s)
| | - Igor G Nikolov
- a Department of Dialysis , University Hospital of Nephrology , Skopje , R. Macedonia
| | | | - Sami Mena
- c Special Hospital for Nephrology and Dialysis , Struga , R. Macedonia , and
| | - Lionel Rostaing
- d Department of Nephrology , Dialysis and Organ Transplantation , CHU Rangueil , Toulouse , France
| | - Aleksandar Dimovski
- b Faculty of Pharmacy , University "Ss Cyril and Methodius" , Skopje , R. Macedonia
| | - Aleksandar Sikole
- a Department of Dialysis , University Hospital of Nephrology , Skopje , R. Macedonia
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