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Context: HCV infection in patients with chronic kidney disease (CKD) is important to be treated because it's associated with increased healthcare costs, utilization and is pertained with decrease in survival rate of HCV-infected patients who also have chronic kidney disease. Direct acting agents (DAAs) are novel form of treatment of HCV infection in patients with CKD. The aim of this study is meta-analysis and comparison of the efficacy of different regimen of DAAs used in the treatment of HCV in such patients.
Objective: Hepatitis C is a liver disease caused by the hepatitis C virus, the virus can cause both acute and chronic hepatitis. Hepatitis C virus (HCV) is a known risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD). HCV infection in CKD patients is also associated with increased healthcare costs and utilization, with further increases in those with ESRD. It should be also noted that survival among HCV-infected patients with chronic kidney disease without undertaking any treatment is low, various mechanisms such as increased liver-related mortality, low quality of life and high cardiovascular risk can explain this finding. The benefits of treatment may extend beyond the liver, with improvements in both cardiovascular and renal outcomes in patient with chronic kidney disease. Previously PEG-INTERFRON Based regimens have been used for treatment of CKD or ESRD Patients with chronic Hepatitis C but this treatment plan was associated with higher adverse effects and less efficacy. Nowadays new researches have shown the efficacy of the Direct Anti-Viral Agents (DAAs) In such patients.
Data Sources: A systematic literature searches in PubMed, EMBASE, Web of Science, and Scopus motor searches was done. Virologic response at 12 weeks after the end of treatment (SVR12) was extract from the included studies. Finally, SVR12 rate with 95% confidence intervals (CI) were pool analyzed with random-effects model.
Study Selection: Studies were included if they satisfied the following criteria: Participants being adult HCV patients with stage 3–5 CKD (age≥18 years), Interventions being DAA-based antiviral therapies, Outcomes being sustained virologic response at 12 weeks after the end of treatment (SVR12). Studies were excluded if having incomplete outcome data and had no sufficient data to calculate SVR12.
Data Extraction: The methodological quality of included observational studies was assessed by three reviewers independently by using the Newcastle–Ottawa scale (NOS), which is usually used for observational studies in meta-analyses.
Results: 20 studies comprising a total of 628 patients (from 20 studies) were included for our meta-analysis. The pooled analysis for SVR12 rate was 0.95 (95% Cl 0.92-0.96, I2= 0.00%), 0.92 (95% Cl 0.82-0.96 I2= 0.00%) and 0.95 (95% Cl 0.93-0.97, I2= 0.0%) for total population, sofosbuvir base treatment group and non sofosbuvir base treatment group.
Conclusion: DDAs have high efficacy in treatment of HCV in patient with CKD and it seems that there is no different between sofosbuvir versus non sofosbuvir based regimens for treatment of HCV infection in this patients.
Chen YC, Lin HY, Li CY, Lee MS, Su YC. A nationwide cohort study suggests that hepatitis C virus infection is associated with increased risk of chronic kidney disease. Kidney International. 2014;85(5): 1200-7.
Solid CA, Peter SA, Natwick T, Guo H, Collins AJ, Arduino JM. Impact of renal disease on patients with hepatitis C: A retrospective analysis of disease burden, clinical outcomes, and health care utilization and cost. Nephron. 2017;136(2): 54-61.
Kasiske BL, Zeier MG, Chapman JR, Craig JC, Ekberg H, Garvey CA, et al. KDIGO clinical practice guideline for the care of kidney transplant recipients: A summary. Kidney International. 2010;77(4):299-311.
Fabrizi F, Martin P, Messa P. New treatment for hepatitis C in chronic kidney disease, dialysis, and transplant. Kidney international. 2016;89(5):988-94.
Puenpatom A, Hull M, McPheeters J, Schwebke K. Disease burden, early discontinuation, and healthcare costs in Hepatitis C patients with and without Chronic Kidney disease treated with interferon-free direct-acting antiviral regimens. Clinical drug investigation. 2017; 37(7):687-97.
Kellum JA, Lameire N, Aspelin P, Barsoum RS, Burdmann EA, Goldstein SL, et al. Kidney disease: Improving global outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury. Kidney International Supplements. 2012;2(1):1-138.
Roth D, Nelson DR, Bruchfeld A, Liapakis A, Silva M, Monsour Jr H, et al. 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. The Lancet. 2015;386(10003):1537-45.
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 International. 2016;36(6): 798-801.
Ram BK, Frank C, Adam P, Cynthia L, Maria H, Lennox J, et al. Safety, efficacy and tolerability of half-dose sofosbuvir plus simeprevir in treatment of Hepatitis C in patients with end stage renal disease. Journal of hepatology. 2015;63(3):763-5.
Lens S, Rodriguez Tajes S, Llovet L-P, Maduell F, Londoño MC. Treating hepatitis C in patients with renal failure. Digestive Diseases. 2017;35(4):339-46.
Kusnir J, Roth D, editors. Direct‐acting antiviral agents for the hepatitis C virus‐infected chronic kidney disease population: The dawn of a New Era. Seminars in dialysis; Wiley Online Library; 2016.
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. PLoS Medicine. 2009;6(7):e1000100.
Castillo JJ, Mull N, Reagan JL, Nemr S, Mitri J. Increased incidence of non-Hodgkin lymphoma, leukemia and myeloma in patients with diabetes mellitus type 2: A meta-analysis of observational studies. Blood. 2012;blood-2011-06-362830.
Pockros PJ, Reddy KR, Mantry PS, Cohen E, Bennett M, Sulkowski MS, et al. Efficacy of direct-acting antiviral combination for patients with hepatitis C virus genotype 1 infection and severe renal impairment or end- stage renal disease. Gastroentero-logy. 2016;150(7):1590-8.
Hundemer GL, Sise ME, Wisocky J, Ufere N, Friedman LS, Corey KE, et al. Use of sofosbuvir-based direct-acting antiviral therapy for hepatitis C viral infection in patients with severe renal insufficiency. Infectious Diseases. 2015;47(12):924-9.
Gane EJ, Sola R, Cohen E, Roberts SK, George J, Skoien R, et al. editors. RUBY-II: Efficacy and safety of a ribavirin-free ombitasvir/paritaprevir/ritonavir+/-asabuvir regimen in patients with severe renal impairment or end-stage renal disease and HCV genotypes 1a or 4 infection. Hepatology; Wiley-Blackwell 111 River st, Hoboken 07030-5774, NJ USA; 2016.
Gane E, Lawitz E, Pugatch D, Papatheodoridis G, Bräu N, Brown A, et al. Expedition-4: Efficacy and safety of glecaprevir/pibrentasvir (ABT-493/ABT-530) in patients with renal impairment and chronic hepatitis C virus genotype 1–6 infection. Hepatology. 2016;64(6):1125A.
Toyoda H, Kumada T, Tada T, Takaguchi K, Ishikawa T, Tsuji K, et al. Safety and efficacy of dual direct-acting antiviral therapy (daclatasvir and asunaprevir) for chronic hepatitis C virus genotype 1 infection in patients on hemodialysis. Journal of gastroenterology. 2016;51(7): 741-7.
Desnoyer A, Pospai D, Lê M, Gervais A, Heurgué-Berlot A, Laradi A, et al. Sofosbuvir-containing regimen for HCV infection in hemodialysis patients: 400 mg daily or only on the day of hemodialysis. J Hepatol. 2016;65:40-7.
Muñoz‐Gómez R, Rincón D, Ahumada A, Hernández E, Devesa M, Izquierdo S, et al. Therapy with ombitasvir/ paritaprevir/ ritonavir plus dasabuvir is effective and safe for the treatment of genotypes 1 and 4 hepatitis C virus (HCV) infection in patients with severe renal impairment: A multicentre experience. Journal of viral hepatitis. 2017;24(6):464-71.
Sato K, Hosonuma K, Yamazaki Y, Kobayashi T, Takakusagi S, Horiguchi N, et al. Combination therapy with ombitasvir/paritaprevir/ritonavir for dialysis patients infected with hepatitis C virus: A prospective multi-institutional study. The Tohoku Journal of Experimental Medicine. 2017;241(1):45-53.
Ponziani FR, Siciliano M, Lionetti R, Pasquazzi C, Gianserra L, D’Offizi G, et al. Effectiveness of paritaprevir/ ritonavir/ ombitasvir/ dasabuvir in hemodialysis patients with hepatitis C virus infection and advanced liver fibrosis. American Journal of Kidney Diseases. 2017;70(2):297- 300.
Welzel T, Hinrichsen H, Sarrazin C, Buggisch P, Baumgarten A, Christensen S, et al. Real‐world experience with the all‐oral, interferon‐ free regimen of ombitasvir/ paritaprevir/ ritonavir and dasabuvir for the treatment of chronic hepatitis C virus infection in the German Hepatitis C Registry. Journal of viral hepatitis. 2017;24(10):840-9.
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 International. 2016;36(6):802-6.
Aggarwal A, Yoo ER, Perumpail RB, Cholankeril G, Kumari R, Daugherty TJ, et al. Sofosbuvir use in the setting of end-stage renal disease: A single center experience. Journal of Clinical and Translational Hepatology. 2017;5(1):23.
Sperl J, Kreidlova M, Merta D, Chmelova K, Senkerikova R, Frankova S. Paritaprevir/ ritonavir/ ombitasvir plus dasabuvir regimen in the treatment of genotype 1 chronic hepatitis C infection in patients with severe renal impairment and end-stage renal disease: A real-life cohort. Kidney and Blood Pressure Research. 2018;43(2):594-605.
Singh A, Kumari S, Leishangthem B, Singh V, editors. Sofosbuvir with NS5A Inhibitors in Hepatitis C Virus (HCV) Infected Renal Transplant Recipients. Hepatology; Wiley 111 River st, Hoboken 07030-5774, NJ USA; 2018.
Suda G, Kudo M, Nagasaka A, Furuya K, Yamamoto Y, Kobayashi T, et al. Efficacy and safety of daclatasvir and asunaprevir combination therapy in chronic hemodialysis patients with chronic hepatitis C. Journal of Gastroenterology. 2016; 51(7):733-40.
Miyazaki R, Miyagi K. Effect and safety of daclatasvir‐ asunaprevir combination therapy for chronic hepatitis C virus genotype 1b‐infected patients on hemodialysis. Therapeutic Apheresis and Dialysis. 2016;20(5):462-7.
Kawakami Y, Imamura M, Ikeda H, Suzuki M, Arataki K, Moriishi M, et al. Pharmacokinetics, efficacy and safety of daclatasvir plus asunaprevir in dialysis patients with chronic hepatitis C: Pilot study. Journal of viral hepatitis. 2016; 23(11):850-6.
Fernández I, Muñoz-Gómez R, Pascasio JM, Baliellas C, Polanco N, Esforzado N, et al. Efficacy and tolerability of interferon-free antiviral therapy in kidney transplant recipients with chronic hepatitis C. Journal of hepatology. 2017;66(4):718-23.
Lee J-J, Lin M-Y, Yang Y-H, Lu S-N, Chen H-C, Hwang S-J. Association of hepatitis C and B virus infection with CKD in an endemic area in Taiwan: A cross-sectional study. American Journal of Kidney Diseases. 2010;56(1):23-31.
Dai CY, Yeh ML, Huang CF, Hou CH, Hsieh MY, Huang JF, et al. Chronic hepatitis C infection is associated with insulin resistance and lipid profiles. Journal of Gastroenterology and Hepatology. 2015;30(5):879-84.
Mendizabal M, Reddy K. Chronic hepatitis C and chronic kidney disease: Advances, limitations and unchartered territories. Journal of viral hepatitis. 2017;24(6):442-53.
Hsu YC, Ho HJ, Huang YT, Wang HH, Wu MS, Lin JT, et al. Association between antiviral treatment and extrahepatic outcomes in patients with hepatitis C virus infection. Gut. 2015;64(3):495-503.
Dumortier J, Guillaud O, Gagnieu M-C, Janbon B, Juillard L, Morelon E, et al. Anti-viral triple therapy with telaprevir in haemodialysed HCV patients: Is it feasible? Journal of Clinical Virology. 2013;56(2):146-9.
Dumortier J, Bailly F, Pageaux G-P, Vallet-Pichard A, Radenne S, Habersetzer F, et al. Sofosbuvir-based antiviral therapy in hepatitis C virus patients with severe renal failure. Nephrology Dialysis Transplantation. 2016;32(12):2065-71.
Li T, Qu Y, Guo Y, Wang Y, Wang L. Efficacy and safety of DAA-based antiviral therapies for HCV patients with stage 4-5 chronic kidney disease: A meta-analysis. Liver international: Official journal of the International Association for the Study of the Liver. 2016;36:1-8.