{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T12:29:35Z","timestamp":1787574575605,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Direct-acting antiviral (DAA) therapy has dramatically transformed the management of hepatitis C virus (HCV) infection in chronic kidney disease (CKD). Severe renal impairment and dialysis dependence are no longer considered major barriers to virologic cure. The main difficulties have shifted toward efficient diagnosis, choosing the regimen in the presence of cirrhosis and drug interactions, coordinating treatment with kidney transplantation, managing HCV-associated immune-complex kidney disease, and providing treatment in dialysis and resource-limited settings. This narrative review aims to discuss these issues in a decision-oriented manner, using verified guidelines, systematic reviews, important clinical trials, transplant cohorts, and studies of cryoglobulinemic disease, while explicitly comparing the strength and consistency of the underlying evidence and highlighting areas of genuine clinical uncertainty. Present evidence supports using the recommended DAA regimens without renal dose adjustment, while ribavirin needs dose modification when kidney function is reduced and can result in hemolytic anemia. Kidneys from HCV-viremic donors can be transplanted to recipients without HCV infection when proper informed consent, rapid access to DAA treatment, and organized post-transplant monitoring are available, although the minimum effective duration of peri-transplant antiviral prophylaxis remains unresolved. Antiviral therapy is the first-line treatment for HCV-associated glomerular disease, while rituximab-based immunosuppression is largely reserved for severe, rapidly progressive, or persistent cryoglobulinemic vasculitis. Future progress will depend less on proving antiviral efficacy and more on closing the gaps between screening, confirmatory testing, starting treatment, transplantation pathways, and long-term follow-up, gaps that stem from inequities in diagnostic infrastructure, drug reimbursement, and healthcare-system organization as much as from any remaining biomedical uncertainty.<\/jats:p>","DOI":"10.3390\/jcm15176504","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:47:19Z","timestamp":1787572039000},"page":"6504","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hepatitis C in Chronic Kidney Disease After the DAA Revolution: Clinical Decisions, Transplantation, and Implementation Challenges"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9353-6520","authenticated-orcid":false,"given":"Mostafa","family":"Mohrag","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Someili","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwa","family":"Elmakki","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6057-9858","authenticated-orcid":false,"given":"Mohammed","family":"Abdulrasak","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Malm\u00f6, Lund University, 203 13 Malmo, Sweden"},{"name":"Department of Gastroenterology and Nutrition, Skane University Hospital, 205 02 Malmo, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S129","DOI":"10.1016\/j.kint.2022.07.013","article-title":"KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease","volume":"102","author":"Jadoul","year":"2022","journal-title":"Kidney Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3801","DOI":"10.1007\/s10620-015-3801-y","article-title":"Hepatitis C Virus Infection Increases the Risk of Developing Chronic Kidney Disease: A Systematic Review and Meta-Analysis","volume":"60","author":"Fabrizi","year":"2015","journal-title":"Dig. Dis. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/hep.29505","article-title":"Chronic Hepatitis C Virus (HCV) Increases the Risk of Chronic Kidney Disease (CKD) While Effective HCV Treatment Decreases the Incidence of CKD","volume":"67","author":"Park","year":"2017","journal-title":"Hepatology"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kenfack-Momo, R., Ngounoue, M.D., Kenmoe, S., Takuissu, G.R., Ebogo-Belobo, J.T., Kengne-Nd\u00e9, C., Mbaga, D.S., Menkem, E.Z., Fogang, R.L., and Tchatchouang, S. (2024). Global Epidemiology of Hepatitis C Virus in Dialysis Patients: A Systematic Review and Meta-Analysis. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0284169"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.ekir.2022.11.008","article-title":"A Systematic Review of Direct-Acting Antivirals for Hepatitis C in Advanced CKD","volume":"8","author":"Balk","year":"2022","journal-title":"Kidney Int. Rep."},{"key":"ref_6","unstructured":"(2026, July 19). AASLD-IDSA HCV Guidance Panel. Persons with Renal Impairment. HCV Guidance: Recommendations for Testing, Man-aging, and Treating Hepatitis C. Available online: https:\/\/www.hcvguidelines.org\/guidance\/patients-with-renal-impairment\/."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.rr6902a1","article-title":"CDC Recommendations for Hepatitis C Screening among Adults\u2014United States, 2020","volume":"69","author":"Schillie","year":"2020","journal-title":"MMWR Recomm. Rep."},{"key":"ref_8","unstructured":"(2026, July 19). AASLD-IDSA HCV Guidance Panel. HCV Testing and Linkage to Care. HCV Guidance: Recommendations for Testing, Manag-ing, and Treating Hepatitis C. Available online: https:\/\/www.hcvguidelines.org\/guidance\/hcv-testing-and-linkage-to-care\/."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"345","DOI":"10.7326\/M16-0065","article-title":"Hepatitis C Core Antigen Testing for Diagnosis of Hepatitis C Virus Infection","volume":"165","author":"Freiman","year":"2016","journal-title":"Ann. Intern. Med."},{"key":"ref_10","unstructured":"World Health Organization (2022). Updated Recommendations on Simplified Service Delivery and Diagnostics for Hepatitis C Infection: Policy Brief, World Health Organization. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789240052697."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Bhattacharya, D., Aronsohn, A., Price, J., Lo Re, V., the American Association for the Study of Liver Diseases\u2013Infectious Diseases Society of America HCV Guidance Panel, Heald, J., Demisashi, G., Durzy, E., Davis-Owino, A., and Tynes, S. (2023). Hepatitis C Guidance 2023 Update: American Association for the Study of Liver Diseases\u2013 Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Clin. Infect. Dis., ciad319.","DOI":"10.1093\/cid\/ciad319"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1016\/S0140-6736(15)00349-9","article-title":"Grazoprevir plus Elbasvir in Treatment-Naive and Treatment-Experienced Patients with Hepatitis C Virus Genotype 1 Infection and Stage 4\u20135 Chronic Kidney Disease (the C-SURFER Study): A Combination Phase 3 Study","volume":"386","author":"Roth","year":"2015","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1056\/NEJMoa1704053","article-title":"Glecaprevir and Pibrentasvir in Patients with HCV and Severe Renal Impairment","volume":"377","author":"Gane","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1111\/liv.14320","article-title":"Efficacy and Safety of Glecaprevir\/Pibrentasvir in Renally Impaired Patients with Chronic HCV Infection","volume":"40","author":"Lawitz","year":"2019","journal-title":"Liver Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1111\/apt.16830","article-title":"Sofosbuvir and Risk of Estimated Glomerular Filtration Rate Decline or End-stage Renal Disease in Patients with Renal Impairment","volume":"55","author":"Sulkowski","year":"2022","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s12985-019-1140-x","article-title":"Sofosbuvir-Based Regimen Is Safe and Effective for Hepatitis C Infected Patients with Stage 4\u20135 Chronic Kidney Disease: A Systematic Review and Meta-Analysis","volume":"16","author":"Li","year":"2019","journal-title":"Virol. J."},{"key":"ref_17","unstructured":"(2026, July 19). AASLD-IDSA HCV Guidance Panel. Monitoring Patients Who Are Starting HCV Treatment, Are on Treatment, or Have Completed Therapy. Available online: https:\/\/www.hcvguidelines.org\/guidance\/monitoring-patients-who-are-starting-hcv-treatment-are-on-treatment-or-have-completed-therapy\/."},{"key":"ref_18","unstructured":"(2026, July 19). AASLD-IDSA HCV Guidance Panel. Persons with Decompensated Cirrhosis. Available online: https:\/\/www.hcvguidelines.org\/guidance\/patients-with-decompensated-cirrhosis\/."},{"key":"ref_19","unstructured":"(2026, July 19). AASLD-IDSA HCV Guidance Panel. Kidney Transplant Recipients. Available online: https:\/\/www.hcvguidelines.org\/guidance\/kidney-transplant-patients\/."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"109","DOI":"10.7326\/M16-1205","article-title":"Treatment with Ledipasvir\u2013Sofosbuvir for 12 or 24 Weeks in Kidney Transplant Recipients with Chronic Hepatitis C Virus Genotype 1 or 4 Infection","volume":"166","author":"Colombo","year":"2016","journal-title":"Ann. Intern. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1002\/hep.30046","article-title":"Glecaprevir\/Pibrentasvir Treatment in Liver or Kidney Transplant Patients with Hepatitis C Virus Infection","volume":"68","author":"Reau","year":"2018","journal-title":"Hepatology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1056\/NEJMc1705221","article-title":"Trial of Transplantation of HCV-Infected Kidneys into Uninfected Recipients","volume":"376","author":"Goldberg","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"533","DOI":"10.7326\/M17-2871","article-title":"Direct-Acting Antiviral Prophylaxis in Kidney Transplantation from Hepatitis C Virus\u2013Infected Donors to Noninfected Recipients","volume":"168","author":"Durand","year":"2018","journal-title":"Ann. Intern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2678","DOI":"10.1681\/ASN.2020050686","article-title":"Multicenter Study to Transplant Hepatitis C\u2013Infected Kidneys (MYTHIC): An Open-Label Study of Combined Glecaprevir and Pibrentasvir to Treat Recipients of Transplanted Kidneys from Deceased Donors with Hepatitis C Virus Infection","volume":"31","author":"Sise","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1053\/j.ajkd.2022.12.019","article-title":"Kidney Transplantation from Hepatitis C Virus\u2013Infected Donors to Uninfected Recipients: A Systematic Review for the KDIGO 2022 Hepatitis C Clinical Practice Guideline Update","volume":"82","author":"Gordon","year":"2023","journal-title":"Am. J. Kidney Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1001\/jama.2022.12868","article-title":"Five-Year Allograft Survival for Recipients of Kidney Transplants from Hepatitis C Virus Infected vs Uninfected Deceased Donors in the Direct-Acting Antiviral Therapy Era","volume":"328","author":"Schaubel","year":"2022","journal-title":"JAMA"},{"key":"ref_27","unstructured":"AASLD-IDSA HCV Guidance Panel (2026, July 19). Treatment of HCV-Uninfected Transplant Recipients Receiving Organs from HCV-Viremic Donors. Available online: https:\/\/www.hcvguidelines.org\/guidance\/treatment-of-hcv-uninfected-transplant-recipients-receiving-organs-from-hcv-viremic-donors\/."},{"key":"ref_28","first-page":"586","article-title":"Direct-Acting Antiviral Therapy Improves Kidney Survival in Hepatitis C Virus-Associated Cryoglobulinaemia: The RENALCRYOGLOBULINEMIC Study","volume":"14","author":"Carbayo","year":"2020","journal-title":"Clin. Kidney J."},{"key":"ref_29","first-page":"843","article-title":"A Randomized Controlled Trial of Rituximab for the Treatment of Severe Cryoglobulinemic Vasculitis","volume":"64","author":"Quartuccio","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1002\/art.34322","article-title":"A Randomized Controlled Trial of Rituximab Following Failure of Antiviral Therapy for Hepatitis C Virus\u2013Associated Cryoglobulinemic Vasculitis","volume":"64","author":"Sneller","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_31","unstructured":"Centers for Disease Control and Prevention (2001). Recommendations for preventing transmission of infections among chronic hemodialysis patients. MMWR Recomm. Rep., 50, 1\u201343."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.ajic.2008.05.013","article-title":"Mathematical Modeling of Hepatitis C Virus Transmission in Hemodialysis","volume":"37","author":"Laporte","year":"2008","journal-title":"Am. J. Infect. Control"},{"key":"ref_33","first-page":"CD006420","article-title":"Isolation as a Strategy for Controlling the Transmission of Hepatitis C Virus (HCV) Infection in Haemodialysis units","volume":"2016","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1111\/ajt.15664","article-title":"Ultra-Short Duration Direct Acting Antiviral Prophylaxis to Prevent Virus Transmission from Hepatitis C Viremic Donors to Hepatitis C Negative Kidney Transplant Recipients","volume":"20","author":"Gupta","year":"2019","journal-title":"Am. J. Transplant."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3734","DOI":"10.1111\/ajt.16747","article-title":"Outcomes of Short-Duration Antiviral Prophylaxis for Hepatitis C Positive Donor Kidney Transplants","volume":"21","author":"Gupta","year":"2021","journal-title":"Am. J. Transplant."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/S2468-1253(20)30081-9","article-title":"Short-Course, Direct-Acting Antivirals and Ezetimibe to Prevent HCV Infection in Recipients of Organs from HCV-Infected Donors: A Phase 3, Single-Centre, Open-Label Study","volume":"5","author":"Feld","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"215","DOI":"10.7326\/M15-0406","article-title":"Restrictions for Medicaid Reimbursement of Sofosbuvir for the Treatment of Hepatitis C Virus Infection in the United States","volume":"163","author":"Barua","year":"2015","journal-title":"Ann. Intern. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"World Health Organization (2024). Global Hepatitis Report 2024: Action for Access in Low- and Middle-Income Countries, World Health Organization. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789240091672.","DOI":"10.54394\/CJQU6666"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/17\/6504\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T12:07:39Z","timestamp":1787573259000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/17\/6504"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,22]]},"references-count":38,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["jcm15176504"],"URL":"https:\/\/doi.org\/10.3390\/jcm15176504","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,22]]}}}