|
1
|
Akin M, Buldukoglu OC, Adanir H, Suleymanlar I, Dincer D, Yildirim B. Effectiveness and safety of sofosbuvir/ledipasvir ± ribavirin treatment in liver and/or renal transplant patients with chronic hepatitis C: A single-center experience. SAGE Open Med 2018; 6:2050312118781416. [PMID: 29899985 PMCID: PMC5992795 DOI: 10.1177/2050312118781416] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Accepted: 05/14/2018] [Indexed: 12/27/2022] Open
Abstract
Objective: Successful treatment is possible with novel direct-acting oral antiviral agents in solid organ transplant patients with hepatitis C. In this study, the effectiveness and safety of sofosbuvir/ledipasvir ± ribavirin treatment in liver and/or renal transplant patients with chronic hepatitis C were evaluated. Materials and methods: A total of 23 liver and/or renal transplant patients who received sofosbuvir/ledipasvir ± ribavirin for chronic hepatitis C over 12 or 24 weeks were enrolled in the study. The treatment response, clinical and laboratory adverse effects, and effect on immunosuppressive drug levels were assessed. Results: A total of 12 patients had undergone renal transplantation and 11 had undergone liver transplantation. All of the renal transplant patients and 91% of liver transplant patients had genotype 1. In total, 10 renal transplant patients and 4 liver transplant patients had treatment experience. Two renal transplant patients and one liver transplant patient had compensated cirrhosis. Nine renal transplant patients were on tacrolimus, and two were on cyclosporine; all of the liver transplant patients were on tacrolimus-based immunosuppressive therapy. While hepatitis C RNA was negative in 75% of renal transplant patients and 91% of liver transplant patients at week 4, it was negative in all of the patients at the end of treatment and 12 weeks after treatment. Significantly reduced hemoglobin levels were observed in patients administered ribavirin during treatment (p = 0.01). There were no significant differences between the baseline and treatment period values of mean creatinine, estimated glomerular filtration rate, bilirubin, and tacrolimus levels. There were no adverse effects leading to treatment discontinuation. Conclusion: Sofosbuvir/ledipasvir ± ribavirin is quite safe and effective in hepatitis C treatment after liver and/or renal transplantation.
Collapse
Affiliation(s)
- Mete Akin
- Department of Gastroenterology, Akdeniz University Faculty of Medicine, Antalya, Turkey
| | | | - Haydar Adanir
- Department of Gastroenterology, Akdeniz University Faculty of Medicine, Antalya, Turkey
| | - Inci Suleymanlar
- Department of Gastroenterology, Akdeniz University Faculty of Medicine, Antalya, Turkey
| | - Dinc Dincer
- Department of Gastroenterology, Akdeniz University Faculty of Medicine, Antalya, Turkey
| | - Bulent Yildirim
- Department of Gastroenterology, Akdeniz University Faculty of Medicine, Antalya, Turkey
| |
Collapse
|
|
2
|
Nookala AU, Crismale J, Schiano T, Te H, Ahn J, Robertazzi S, Rodigas C, Satoskar R, Kc M, Hassan M, Smith C. Direct-acting antiviral regimens are safe and effective in the treatment of hepatitis C in simultaneous liver-kidney transplant recipients. Clin Transplant 2018; 32:e13198. [PMID: 29323755 DOI: 10.1111/ctr.13198] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/07/2018] [Indexed: 01/17/2023]
Abstract
Hepatitis C (HCV) remains the single most common etiology of end-stage liver disease leading to simultaneous liver/kidney transplant (SLKT) and has worse post-transplant survival compared to non-HCV patients. We aim to assess the effectiveness and tolerance of the all-oral direct-acting antiviral (DAA) agents with or without ribavirin (RBV) in the treatment of HCV recurrence post-SLKT. Thirty-four patients were studied retrospectively, composed predominantly of treatment-naïve (73.5%) non-Caucasian (61.8%) males (82.4%) infected with genotype 1a (64.7%). 94.1% reached a sustained virologic response (SVR) after 24 weeks (32/34 patients), without difference between 12 and 24 weeks of therapy. 64.7% had no clinical side effects. Three deaths occurred, all unrelated to treatment. One patient had liver rejection; tacrolimus was increased and prednisone was initiated while HCV treatment was continued and the patient ultimately achieved SVR. No liver graft losses. No kidney rejection or losses. We demonstrated that DAA combinations with or without RBV result in a remarkable SVR rate and tolerated in the majority of the studied SLKT patients. It is safe to wait to treat until post-kidney transplant and therefore increase the donor pool for these patients. Our cohort is ethnically diverse, making our results generalizable.
Collapse
Affiliation(s)
| | | | | | - Helen Te
- University of Chicago Medicine, Chicago, IL, USA
| | - Joseph Ahn
- Oregon Health and Sciences University, Portland, OR, USA
| | | | - Colleen Rodigas
- MedStar Georgetown Transplant Institute, Washington, DC, USA
| | - Rohit Satoskar
- MedStar Georgetown Transplant Institute, Washington, DC, USA
| | - Mandip Kc
- University of Minnesota, Minneapolis, MN, USA
| | | | - Coleman Smith
- MedStar Georgetown Transplant Institute, Washington, DC, USA
| |
Collapse
|
|
3
|
Kwok RM, Ahn J, Schiano TD, Te HS, Potosky DR, Tierney A, Satoskar R, Robertazzi S, Rodigas C, Lee Sang M, Wiegel J, Patel N, Gripshover J, Hassan MA, Branch A, Smith CI. Sofosbuvir plus ledispasvir for recurrent hepatitis C in liver transplant recipients. Liver Transpl 2016; 22:1536-1543. [PMID: 27543748 DOI: 10.1002/lt.24614] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2016] [Accepted: 08/08/2016] [Indexed: 12/14/2022]
Abstract
Hepatitis C virus (HCV) recurrence after liver transplantation (LT) is associated with worse outcomes. The combination of ledipasvir (LDV) and sofosbuvir (SOF) has been approved for HCV treatment after LT, but there are limited data on the effectiveness and safety of LDV/SOF in the "real-world" setting. This multicenter study is the largest report to date on the effectiveness and safety of LDV/SOF in the post-LT setting. A total of 204 patients (72% male, 68% Caucasian, 66% genotype [GT] 1a, 21% METAVIR F3-F4, 49% treatment-experienced) were treated with LDV/SOF. The mean duration from LT to treatment initiation was 4.8 years. The overall sustained virological response rate 12 weeks after completion of therapy (SVR12) was 96%. Patients treated with 8 or 12 weeks of LDV/SOF without RBV experienced an SVR12 rate of 100% and 96%, respectively. Calcineurin inhibitors were used in 89% of patients, and 32% of patients underwent adjustment in immunosuppression during treatment. One episode of mild rejection, responsive to an increase in immunosuppression dosage, was observed. There was no graft loss attributed to HCV treatment. Four deaths occurred unrelated to HCV treatment, and no significant serious adverse events were documented. In conclusion, SOF and LDV with or without RBV for 8, 12, or 24 weeks in post-LT patients was effective and safe with a high SVR12 rate across a spectrum of GTs and stages of fibrosis. Liver Transplantation 22 1536-1543 2016 AASLD.
Collapse
Affiliation(s)
- Ryan M Kwok
- Medstar Georgetown Transplant Institute, Georgetown University School of Medicine, Washington, DC.
| | - Joseph Ahn
- Oregon Health and Science University, Portland, OR
| | - Thomas D Schiano
- Division of Liver Diseases and Recanati-Miller Transplant Institute, Mount Sinai Medical Center, New York, NY
| | - Helen S Te
- Center for Liver Diseases, Department of Medicine, The University of Chicago Medical Center, Chicago, IL
| | - Darryn R Potosky
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD
| | - Amber Tierney
- University of Minnesota Medical School, Minneapolis, MN
| | - Rohit Satoskar
- Medstar Georgetown Transplant Institute, Georgetown University School of Medicine, Washington, DC
| | - Suzanne Robertazzi
- Medstar Georgetown Transplant Institute, Georgetown University School of Medicine, Washington, DC
| | - Colleen Rodigas
- Medstar Georgetown Transplant Institute, Georgetown University School of Medicine, Washington, DC
| | - Michelle Lee Sang
- Medstar Georgetown Transplant Institute, Georgetown University School of Medicine, Washington, DC
| | | | - Neal Patel
- Division of Liver Diseases and Recanati-Miller Transplant Institute, Mount Sinai Medical Center, New York, NY
| | - Janet Gripshover
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD
| | | | - Andrea Branch
- Division of Liver Diseases and Recanati-Miller Transplant Institute, Mount Sinai Medical Center, New York, NY
| | - Coleman I Smith
- Medstar Georgetown Transplant Institute, Georgetown University School of Medicine, Washington, DC
| |
Collapse
|
|
5
|
Fagiuoli S, Ravasio R, Lucà MG, Baldan A, Pecere S, Vitale A, Pasulo L. Management of hepatitis C infection before and after liver transplantation. World J Gastroenterol 2015; 21:4447-56. [PMID: 25914454 PMCID: PMC4402292 DOI: 10.3748/wjg.v21.i15.4447] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Revised: 02/11/2015] [Accepted: 03/12/2015] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C (CHC) is the most common indication for liver transplantation (LT). Aggressive treatment of hepatitis C virus (HCV) infection before cirrhosis development or decompensation may reduce LT need and risk of HCV recurrence post-LT. Factors associated with increased HCV risk or severity of recurrence include older age, immunosuppression, HCV genotype 1 and high viral load at LT. HCV recurrence post-LT leads to accelerated liver disease and cirrhosis development with reduced graft and patient survival. Currently, interferon (IFN)-based regimens can be used in dual-agent regimens with ribavirin, in triple-agent antiviral strategies with direct-acting antivirals (e.g., protease inhibitors telaprevir or boceprevir), or before transplant in compensated patients to reduce HCV viral load to prevent or reduce the risk of post-LT recurrence and complications; they cannot be used in patients with decompensated cirrhosis. IFN-based regimens are used in less than half of HCV-infected patients waiting for LT due to extremely low efficacy and poor tolerability. However, antiviral therapy is indicated after LT in patients with histologically confirmed CHC despite tolerability issues. Improvements in side effect management have increased survival in patients achieving therapeutic targets. HCV treatment pre- and post-LT results in significant health care costs especially when lack of efficacy leads to disease worsening, although studies have shown sofosbuvir treatment before LT vs conventional post-LT dual antiviral is cost effective. The suboptimal efficacy and tolerability of IFN-based therapies, plus the significant economic burden, means the need for effective and well tolerated IFN-free anti-HCV therapy for pre- and post-LT remains high.
Collapse
|
|
6
|
Karnik GS, Shetty K. Management of recurrent hepatitis C in orthotopic liver transplant recipients. Infect Dis Clin North Am 2013; 27:285-304. [PMID: 23714341 DOI: 10.1016/j.idc.2013.02.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
End-stage liver disease and hepatocellular carcinoma from chronic hepatitis C are the most common indications for orthotopic liver transplantation and the incidence of both are projected to increase over the next decade. Recurrent hepatitis C virus infection of the allograft is associated with an accelerated progression to cirrhosis, graft loss, and death. This article presents an overview of the natural history of hepatitis C virus recurrence in liver transplant recipients and guidance on optimal management strategies.
Collapse
Affiliation(s)
- Geeta S Karnik
- Department of Infectious Diseases, Georgetown University Hospital, Washington, DC 20007, USA.
| | | |
Collapse
|