Grazoprevir plus elbasvir in HCV genotype-1 or -4 infected patients with stage 4/5 severe chronic kidney disease is safe and effective
2018; Elsevier BV; Volume: 94; Issue: 1 Linguagem: Inglês
10.1016/j.kint.2018.02.019
ISSN1523-1755
AutoresLaurent Alric, Isabelle Ollivier‐Hourmand, Emilie Bérard, Sophie Hillaire, Maéva Guillaume, Anaı̈s Vallet-Pichard, Brigitte Bernard‐Chabert, V. Loustaud‐Ratti, Marc Bourlière, Victor de Lédinghen, I. Fouchard‐Hubert, V. Canva, Anne Minello, Eric Nguyen‐Khac, Vincent Leroy, David Saadoun, Dominique Trias, Stanislas Pol, Nassim Kamar,
Tópico(s)Hepatitis B Virus Studies
ResumoPatients with advanced chronic kidney disease who receive direct-acting antiviral drugs require special consideration regarding comorbid conditions. Here we assessed the efficacy and safety of grazoprevir plus elbasvir in 93 patients infected with HCV genotype 1 or 4 and with advanced chronic kidney disease in a non-randomized, multicenter, nationwide observational survey. Twenty patients with HCV genotype 1a, 51 patients with 1b, four unclassified genotype 1, 17 with genotype 4 and one with genotype 6 received grazoprevir plus elbasvir (100/50 mg) once daily. All patients had severe chronic kidney disease with 70 patients stage G5, including patients on hemodialysis (74.2%), and 23 were stage G4 chronic kidney disease. Severe liver disease (Metavir F3/F4) was found in 33 patients. A sustained virologic response 12 weeks after the end of therapy was achieved in 87 of 90 patients. Two patients had a virologic breakthrough and one had a relapse after treatment withdrawal. Most patients received many concomitant medications (mean 7.7) related to comorbid conditions. Serious adverse events occurred in six patients, including three deaths while on grazoprevir plus elbasvir, not related to this therapy. Thus, once-daily grazoprevir plus elbasvir was highly effective with a low rate of adverse events in this advanced chronic kidney disease difficult-to-treat population with an HCV genotype 1 or 4 infection. Patients with advanced chronic kidney disease who receive direct-acting antiviral drugs require special consideration regarding comorbid conditions. Here we assessed the efficacy and safety of grazoprevir plus elbasvir in 93 patients infected with HCV genotype 1 or 4 and with advanced chronic kidney disease in a non-randomized, multicenter, nationwide observational survey. Twenty patients with HCV genotype 1a, 51 patients with 1b, four unclassified genotype 1, 17 with genotype 4 and one with genotype 6 received grazoprevir plus elbasvir (100/50 mg) once daily. All patients had severe chronic kidney disease with 70 patients stage G5, including patients on hemodialysis (74.2%), and 23 were stage G4 chronic kidney disease. Severe liver disease (Metavir F3/F4) was found in 33 patients. A sustained virologic response 12 weeks after the end of therapy was achieved in 87 of 90 patients. Two patients had a virologic breakthrough and one had a relapse after treatment withdrawal. Most patients received many concomitant medications (mean 7.7) related to comorbid conditions. Serious adverse events occurred in six patients, including three deaths while on grazoprevir plus elbasvir, not related to this therapy. Thus, once-daily grazoprevir plus elbasvir was highly effective with a low rate of adverse events in this advanced chronic kidney disease difficult-to-treat population with an HCV genotype 1 or 4 infection. The prevalence of hepatitis C virus (HCV) infection in patients with end-stage renal disease (ESRD), despite its prevalence declining over time, remains 4 times greater in dialysis patients and kidney-transplant recipients than in the general population.1Butt A.A. Wang X. Fried L.F. HCV infection and the incidence of CKD.Am J Kidney Dis. 2011; 57: 396-402Google Scholar, 2Goodkin D.A. Bieber B. Gillespie B. et al.Hepatitis C infection is very rarely treated among hemodialysis patients.Am J Nephrol. 2013; 38: 405-412Google Scholar, 3Isnard Bagnis C. Couchoud C. Bowens M. et al.Epidemiology update for hepatitis C virus and hepatitis B virus in end-stage renal disease in France.Liver Int. 2017; 37: 820-826Google Scholar, 4Ladino M. Pedraza F. Roth D. Hepatitis C virus infection in chronic kidney disease.J Am Soc Nephrol. 2016; 27: 2238-2246Scopus (44) Google Scholar In the general population, apart from its impact on the liver, chronic HCV infection is associated with increased global mortality related to higher rates of diabetes, neurologic stroke, and cardiovascular disease. In addition, HCV infection increases the risk of chronic kidney disease (CKD), leading to ESRD.5Hsu Y.-C. Ho H.J. Huang Y.-T. et al.Association between antiviral treatment and extrahepatic outcomes in patients with hepatitis C virus infection.Gut. 2015; 64: 495-503Google Scholar After renal transplantation, HCV infection is an independent factor for global mortality and the loss of the kidney graft.6Fabrizi F. Martin P. Dixit V. et al.Hepatitis C virus antibody status and survival after renal transplantation: meta-analysis of observational studies.Am J Transplant. 2005; 5: 1452-1461Google Scholar This worse prognosis in HCV-infected kidney recipients is usually thought to be caused in part by a more rapid progression of liver fibrosis and an increased risk of de novo transplant glomerulopathy.7Alric L. Di-Martino V. Selves J. et al.Long-term impact of renal transplantation on liver fibrosis during hepatitis C virus infection.Gastroenterology. 2002; 123: 1494-1499Google Scholar, 8Morales J.M. Fabrizi F. Hepatitis C and its impact on renal transplantation.Nat Rev Nephrol. 2015; 11: 172-182Google Scholar Currently, direct-acting antiviral drugs (DAAs) are the gold standard for treating HCV infection.9Falade-Nwulia O. Suarez-Cuervo C. Nelson D.R. et al.Oral direct-acting agent therapy for hepatitis C virus infection: a systematic review.Ann Intern Med. 2017; 166: 637-648Google Scholar There are numerous types of DAAs, and the combination of at least 2 different classes results in a high sustained virologic response, as defined by an undetectable HCV RNA 12 weeks after the end of therapy (SVR12). Sofosbuvir was the first pan-genotypic DAA to become available. A second wave of DAAs that are active against HCV genotypes 1, 2, 3, 4, 5, and 6 were subsequently approved. A combination of these drugs, with or without ribavirin, has been shown to be effective and well tolerated in treatment-naïve and treatment-experienced patients with HCV infection. Indeed, >90% of HCV patients can be cured of the infection, and an SVR is generally associated with resolution of liver fibrosis in patients without cirrhosis.9Falade-Nwulia O. Suarez-Cuervo C. Nelson D.R. et al.Oral direct-acting agent therapy for hepatitis C virus infection: a systematic review.Ann Intern Med. 2017; 166: 637-648Google Scholar Because sofosbuvir is primarily eliminated by the kidney,10Kanter C.T. Drenth J.P. Arends J.E. et al.Viral hepatitis C therapy: pharmacokinetic and pharmacodynamic considerations.Clin Pharmacokinet. 2014; 53: 409-427Google Scholar its use is not recommended for patients with ESRD, including patients with an estimated glomerular filtration rate (eGFR) <30 ml/min per 1.73 m2 or those receiving hemodialysis. Consequently, the safety and efficacy of sofosbuvir-containing regimens have not been clearly established in such patients. In addition, therapy with DAAs given to CKD patients requires special consideration regarding comorbid conditions and drug-to-drug interactions.10Kanter C.T. Drenth J.P. Arends J.E. et al.Viral hepatitis C therapy: pharmacokinetic and pharmacodynamic considerations.Clin Pharmacokinet. 2014; 53: 409-427Google Scholar, 11Fabrizi F. Martin P. Messa P. New treatment for hepatitis C in chronic kidney disease, dialysis, and transplant.Kidney Int. 2016; 89: 988-994Google Scholar, 12Li T. Qu Y. Guo Y. et al.Efficacy and safety of direct-acting antivirals-based antiviral therapies for hepatitis C virus patients with stage 4-5 chronic kidney disease: a meta-analysis.Liver Int. 2017; 37: 974-981Google Scholar Phase 2 and 3 trials using grazoprevir (GZR), an NS3/4A protease inhibitor, and elbasvir (EBR), an NS5A protein inhibitor of HCV, have shown very good results against HCV genotype 1 and 4 infections.13Lawitz E. Gane E. Pearlman B. et al.Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients infected with hepatitis C virus genotype 1 with cirrhosis or previous null response (C-WORTHY): a randomized, open-label phase 2 trial.Lancet. 2015; 385: 1075-1086Google Scholar, 14Jacobson I.M. Lawitz E. Kwo P.Y. et al.Safety and efficacy of elbasvir/grazoprevir in patients with hepatitis C virus infection and compensated cirrhosis: an integrated analysis.Gastroenterology. 2017; 152: 1372-1382Abstract Full Text Full Text PDF Scopus (76) Google Scholar Less than 1% of GZR+EBR is renally excreted; thus, dose adjustments of GZR+EBR are not needed for patients with nondialysis-dependent stage 4/5 CKD or those who are dialysis dependent. C-Surfer15Roth D. Nelson D.R. Bruchfeld A. 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.Lancet. 2015; 386: 1537-1545Google Scholar was the first randomized, placebo-controlled phase 3 study to evaluate an all-oral, ribavirin-free regimen in HCV genotype 1–infected patients, with stage 4 or 5 advanced CKD, including subjects on hemodialysis. Once-daily GZR+EBR was highly effective, with a low rate of adverse events in patients with advanced CKD and a HCV genotype 1 infection. Taking into account the results of the C-Surfer study, GZR+EBR is a good therapy option for this specific population. In 2015, the French National Agency for Medicine and Health-Product Safety granted nominative temporary authorization (ATUn) for the use of GZR+EBR, which is an early-access program that gives patients access to a medication before it is authorized for marketing. Patients were mainly CKD stage 4/5, infected with HCV genotype 1 or 4, sometimes with a history of kidney or liver transplantation or on a transplantation list, were treatment-naïve or experienced, regardless of fibrosis stage or comorbid conditions. Most of these patients had been excluded from phase 2 or 3 trials. The aims of this multicenter cohort study were to report, in real-life clinical practice, the efficacy and safety of GZR + EBR-based therapy given to HCV-infected patients with advanced CKD and differing clinical profiles. As shown in Figure 1, 93 patients with CKD were included in the study. They were enrolled at 28 centers, and 90 patients reached week 12 of the follow-up after GZR + EBR withdrawal. Three patients died while receiving GZR + EBR; thus, SVR12 was not assessed. The baseline demographic and disease characteristics are shown in Table 1. Most patients were on hemodialysis (69/93, 74.2%). All patients had severe CKD: 70 (75.3%) were stage G5 and 23 (24.7%) were stage G4. The duration of hemodialysis before GZR + EBR treatment was 27.5 ± 3.5 months. Previous anti-HCV treatment with pegylated interferon + ribavirin failed in 37 patients (39.8%). Most patients were HCV genotype 1b (54.8%); the prevalence of HCV genotype 1a (21.5%) or genotype 4 (18.3%) was substantial. At baseline, liver fibrosis was mild in 53 patients (57.0%), and severe liver disease (METAVIR F3/F4) was observed in 33 patients (35.5%); 19 patients (20.4%) were METAVIR F3. Fourteen patients (15.1%) had compensated cirrhosis. Most of the patients (76.3%) received GZR + EBR for 12 weeks, 16.1% for 16 weeks, and only 1 patient for 24 weeks (Table 1). This extended duration of antiviral therapy was for patients with HCV genotype 1a infection or those with cirrhosis. Six patients (6.5%) were treated for 800,000 IU/ml39 (41.9) Missing5 (5.4)HCV treatment history, N (%) Treatment naïve56 (60.2) Previous HCV treatment37 (39.8)Treatment duration, wk, N (%) 1271 (76.3) 1615 (16.1) 241 (1.1) Other6 (6.5)Combination with ribavirin, N (%)3 (3.2)Chronic kidney disease stage, N (%) Stage G423 (24.7) Stage G5, not receiving hemodialysis1 (1) Stage G5, receiving hemodialysis69 (69.8)Previous renal transplantation, N (%)16 (17.2)Patients with functioning kidney allograft, N (%)12 (12.9)Main cause of kidney disease, N (%) Genetic disease6 (6.5) Glomerulonephritis16 (17.2) Tubulointerstitial nephritis7 (7.5) Cryoglobulinemia11 (11.8) Diabetes8 (8.6) Hypertension and nephroangiosclerosis5 (5.4) OtheraVascular nephropathy, tubulointerstitial nephropathy, lupus, hyperoxaluria type 2, cardiorenal syndrome, oligomeganephronic, nephropathy of vesicoureteral reflux, segmental and focal hyalinosis, thrombotic microangiopathy, Henoch-Schönlein purpura.22 (23.7) Undetermined18 (19.3)Comorbidities, N (%) Liver transplanted4 (4.3) HIV coinfected7 (7.5) Diabetes22 (23.7) Hypertension67 (72.0) Dyslipidemia23 (24.7) Cardiac disease35 (37.6) Vascular disease7 (7.5) Respiratory disease4 (4.3) Alcohol uptake11 (11.8) i.v drug addiction1 (1.1) Cancer7 (7.5) Other (not listed)31 (33.3)HCV, hepatitis C virus.Data are N (%) or mean ± SD (range).a Vascular nephropathy, tubulointerstitial nephropathy, lupus, hyperoxaluria type 2, cardiorenal syndrome, oligomeganephronic, nephropathy of vesicoureteral reflux, segmental and focal hyalinosis, thrombotic microangiopathy, Henoch-Schönlein purpura. Open table in a new tab HCV, hepatitis C virus. Data are N (%) or mean ± SD (range). Of the 90 patients who received GZR + EBR and completed the 12-week follow-up after treatment withdrawal, a virologic response at the end of antiviral therapy was observed in 88 patients (97.8%) (Table 2). The primary endpoint (i.e., SVR12), was achieved in 87 patients (96.7%) (95% confidence interval 0.91–0.99). A virologic breakthrough was observed in 2 patients and a relapse in 1 patient (Table 2). Of the 87 patients who achieved an SVR12, 2 patients discontinued treatment prematurely at 5 and 8 weeks, with no effect on virologic response. The first patient stopped treatment because of an adverse event, and 1 patient decided to stop treatment.Table 2Virological responseGrazoprevir + elbasvir treatmentOn hemodialysis (N = 67)Not on hemodialysis (N = 23)Total (N = 90)aDeath occurred in 3 of 93 patients before the end of grazoprevir + elbasvir therapy: 90 patients were analyzed for SVR12.SVR (HCV RNA <LLoQ) End of treatment, N (%)66 (98.5)22 (95.6)88 (97.7) Follow-up week 12, N (%)65 (97)22 (95.7)87 (96.7) Relapse101 Breakthrough112HCV, hepatitis C virus; LLoQ, lower limit of quantification (HCV RNA is detected but <15 mIU/ml); SVR, sustained virological response.Data are N (%).a Death occurred in 3 of 93 patients before the end of grazoprevir + elbasvir therapy: 90 patients were analyzed for SVR12. Open table in a new tab HCV, hepatitis C virus; LLoQ, lower limit of quantification (HCV RNA is detected but 800,000 IU/ml or 1.0 change from baseline. 8.5–11.0 g/dl10 (10.8) 1.0 change from baseline. 1.5–2.5 × baseline2 (2.2) >2.5 × baseline0 (0) >5 × baseline0 (0)Aspartate aminotransferasecData presented for patients with >1.0 change from baseline. 1.5–2.5 × baseline1 (1.1) >2.5 × baseline1 (1.1) >5 × baseline0 (0)BilirubincData presented for patients with >1.0 change from baseline. >2.5–5 × baseline1 (1.1) >5.0–10.0 × baseline0 (0)CreatininecData presented for patients with >1.0 change from baseline. >2.5 × baseline2 (2.1)Data are n (%).a Incidence during the initial treatment period and for 30 days after the completion of treatment (all patients treated).b Back pain, weakness of the legs, abdominal pain, hypercalcemia, arthralgia, amenorrhea, hair loss, and decreased libido.c Data presented for patients with >1.0 change from baseline. Open table in a new tab HCV, hepatitis C virus. Data are n (%). Data regarding change in proteinuria with antiviral therapy were not available in these patients, most of whom were on hemodialysis. Kidney function became impaired between the screening and the initiation of therapy in 8 patients who required starting hemodialysis rapidly. This was unrelated to GZR + EBR. With respect to the 24 nonhemodialysis patients, only 2 (8.3%) had a severe worsening of kidney function during antiviral therapy (Table 4). Three patients (12.5%) had an improvement in eGFR (>10 ml/min) compared with pretreatment values. Overall, the mean eGFR remained unchanged (i.e., 20.5 ± 8.5 ml/min per 1.73 m2 at the initiation of therapy and 21.4 ± 6.9 ml/min per 1.73 m2 at the end of the therapy. No other significant changes in other blood test results were observed during GZR + EBR treatment (Table 4). Serious adverse events occurred in 6 of 93 patients (6.45%), leading to early discontinuation of GZR + EBR in 2 of 90 patients (2.2%). A 41-year-old woman with a previous renal transplantation and cirrhosis had a first episode of ascites during GZR+EBR therapy, but rapidly recovered with diuretics without recurrence. One woman had severe anemia (7.5 g/dl) that required a blood transfusion; she was not on hemodialysis and was noncirrhotic. She did not receive ribavirin. Hepatocellular carcinoma developed in a cirrhotic 64-year-old woman during antiviral therapy that was treated by radiofrequency ablation, but GZR + EBR was not stopped. All 3 patients achieved SVR12. Of the 6 serious adverse events, deaths occurred in 3 of 93 patients (3.2%) during the course of GZR + EBR. A 78-year-old man died of a brain hemorrhage after 38 days of antiviral therapy. A second cirrhotic patient with diabetes who was 58 years old died of severe hypoglycemia followed by multiorgan failure 19 days after GZR + EBR initiation. The last death was a 78-year-old man who died of septic shock a few days after withdrawal of antiviral therapy. These 3 deaths seemed to be more related to comorbid conditions than to the GZR + EBR therapy. Because the 3 patients died during GZR + EBR therapy, HCV RNA was not available at 12 weeks after antiviral therapy withdrawal. Our study confirms that once-daily GZR+EBR is highly effective and has a low rate of adverse events in a real-life population with ESRD and HCV genotype 1 or 4 infection. Extensive treatment of HCV-infected patients with advanced CKD stage 4/5 is a very important issue for many reasons. HCV-infected patients with advanced CKD have an increased risk of all-cause death and liver-related diseases; and the decline of kidney function is also accelerated.4Ladino M. Pedraza F. Roth D. Hepatitis C virus infection in chronic kidney disease.J Am Soc Nephrol. 2016; 27: 2238-2246Scopus (44) Google Scholar In addition, HCV infection decreases patient and graft survival after kidney transplantation.1Butt A.A. Wang X. Fried L.F. HCV infection and the incidence of CKD.Am J Kidney Dis. 2011; 57: 396-402Google Scholar, 4Ladino M. Pedraza F. Roth D. Hepatitis C virus infection in chronic kidney disease.J Am Soc Nephrol. 2016; 27: 2238-2246Scopus (44) Google Scholar The reported prevalence of HCV infection in patients with ESRD varies between 5% and 15%.2Goodkin D.A. Bieber B. Gillespie B. et al.Hepatitis C infection is very rarely treated among hemodialysis patients.Am J Nephrol. 2013; 38: 405-412Google Scholar, 3Isnard Bagnis C. Couchoud C. Bowens M. et al.Epidemiology update for hepatitis C virus and hepatitis B virus in end-stage renal disease in France.Liver Int. 2017; 37: 820-826Google Scholar DOPPS (Dialysis Outcomes and Practice Patterns Study),2Goodkin D.A. Bieber B. Gillespie B. et al.Hepatitis C infection is very rarely treated among hemodialysis patients.Am J Nephrol. 2013; 38: 405-412Google Scholar which provided data on 49,762 dialyzed patients, reported a mean prevalence of HCV infection of 9.5%, and only 1% of HCV-infected patients received antiviral therapy. Among 617 HCV-infected patients on a waiting list for renal transplantation, only 3.7% received antiviral therapy.2Goodkin D.A. Bieber B. Gillespie B. et al.Hepatitis C infection is very rarely treated among hemodialysis patients.Am J Nephrol. 2013; 38: 405-412Google Scholar Combined therapy of pegylated interferon-α ± ribavirin was the first demonstrably effective treatment for HCV infection, but was poorly tolerated in ESRD.16Izopet J. Rostaing L. Moussion F. et al.High rate of hepatitis C virus clearance in hemodialysis patients after interferon-α therapy.J Infect Dis. 1997; 176: 1614-1617Google Scholar This explains the low rate of anti-HCV therapy given to patients with CKD. However, HCV therapy can reduce the progression of liver fibrosis and extrahepatic manifestations in patients with CKD.17Alric L. Plaisier E. Thébault S. et al.Influence of antiviral therapy in hepatitis C virus-associated cryoglobulinemic MPGN.Am J Kidney Dis. 2004; 43: 617-623Google Scholar, 18Saadoun D. Pol S. Ferfar Y. et al.Efficacy and safety of sofosbuvir plus daclatasvir for treatment of HCV-associated cryoglobulinemia vasculitis.Gastroenterology. 2017; 153: 49-52Google Scholar Currently, DAAs are the gold-standard treatment for HCV infection. DAAs result in a high SVR with very good safety in the general population.9Falade-Nwulia O. Suarez-Cuervo C. Nelson D.R. et al.Oral direct-acting agent therapy for hepatitis C virus infection: a systematic review.Ann Intern Med. 2017; 166: 637-648Google Scholar, 19Loannou G.N. Beste L.A. Chang M.F. et al.Effectiveness of sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ritonavir/ombitasvir and dasabuvir regimens for treatment of patients with hepatitis C in the Veterans Affairs national health care system.Gastroenterology. 2016; 151: 457-471Google Scholar Most studies using DAAs have excluded patients with stage 4 to 5 CKD. Indeed, many DAAs have kidney elimination,10Kanter C.T. Drenth J.P. Arends J.E. et al.Viral hepatitis C therapy: pharmacokinetic and pharmacodynamic considerations.Clin Pharmacokinet. 2014; 53: 409-427Google Scholar need potential dose adjustments, and are associated with the risk of drug-to-drug interactions. The few data available on patients with severe kidney disease and treated with current regimens are often from small sample sizes.20Sise M.E. Backman E. Ortiz G.A. et al.Effect of sofosbuvir-based hepatitis C virus therapy on kidney function in patients with CKD.J Am Soc Nephrol. 2017; 12: 1615-1623Google Scholar, 21Singh T. Guirguis J. Anthony S. et al.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: 802-806Google Scholar, 22Saxena V. Koraishy F.M. Sise M.E. et al.Safety and efficacy of sofosbuvir-containing regimens in hepatitis C-infected patients with impaired renal function.Liver Int. 2016; 36: 807-816Google Scholar, 23Dumortier J. Bailly F. Pageaux G.P. et al.Sofosbuvir-based antiviral therapy in hepatitis C virus patients with severe renal failure.Nephrol Dial Transplant. 2016; (pii:gfw348)Google Scholar, 24Bourliere M. Gordon S.C. Flamm S.L. et al.Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection.N Engl J Med. 2017; 376: 2134-2146Google Scholar Sofosbuvir-based therapies have dramatically improved the prognosis of HCV infection. However, sofosbuvir is metabolized into GS-331007, the active form.10Kanter C.T. Drenth J.P. Arends J.E. et al.Viral hepatitis C therapy: pharmacokinetic and pharmacodynamic considerations.Clin Pharmacokinet. 2014; 53: 409-427Google Scholar, 23Dumortier J. Bailly F. Pageaux G.P. et al.Sofosbuvir-based antiviral therapy in hepatitis C virus patients with severe renal failure.Nephrol Dial Transplant. 2016; (pii:gfw348)Google Scholar The kidney is the major organ involved in eliminating sofosbuvir and its metabolites. In patients with severe renal impairment, the pharmacokinetics of sofosbuvir and GS-331007 were 171% and 451% higher, respectively, than in patients with normal renal function.23Dumortier J. Bailly F. Pageaux G.P. et al.Sofosbuvir-based antiviral therapy in hepatitis C virus patients with severe renal failure.Nephrol Dial Transplant. 2016; (pii:gfw348)Google Scholar There was no evidence of clinically relevant consequences from sofosbuvir toxicity.20Sise M.E. Backman E. Ortiz G.A. et al.Effect of sofosbuvir-based hepatitis C virus therapy on kidney function in patients with CKD.J Am Soc Nephrol. 2017; 12: 1615-1623Google Scholar, 21Singh T. Guirguis J. Anthony S. et al.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: 802-806Google Scholar, 22Saxena V. Koraishy F.M. Sise M.E. et al.Safety and efficacy of sofosbuvir-containing regimens in hepatitis
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