ledipasvir and Kidney-Failure--Chronic

Hepatitis C virus (HCV) infection is an independent risk factor associated with adverse outcomes in patients with end-stage renal disease (ESRD). Due to the wide variety of direct-acting antiviral regimens (DAAs) and the factor of renal insufficiency, careless selection of anti-hepatitis C treatment can lead to treatment failure and safety problems. The integrated evidence for optimized therapies for these patients is lacking. This study would conduct comparisons of different DAAs and facilitate clinical decision-making.. We conducted a systematic literature search in multiple databases (PubMed, Ovid, Embase, Cochrane Library, and Web of Science) up to 7 August 2023. Study data that contained patient characteristics, study design, treatment regimens, intention-to-treat sustained virologic response (SVR), and adverse event (AE) data per regimen were extracted into a structured electronic database and analyzed. The network meta-analysis of the estimation was performed by the Bayesian Markov Chain Monte Carlo methods.. Our search identified 5,278 articles; removing the studies with duplicates and ineligible criteria, a total of 62 studies (comprising 4,554 patients) were included. Overall, the analyses contained more than 2,489 male individuals, at least 202 patients with cirrhosis, and no less than 2,377 patients under hemodialysis. Network meta-analyses of the DAAs found that receiving ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (R) plus dasabuvir (DSV), glecaprevir (G)/pibrentasvir (P), and sofosbuvir (SOF)/ledipasvir (LDV) ranked as the top three efficacy factors for the HCV-infected ESRD patients. Stratified by genotype, the G/P would prioritize genotype 1 and 2 patients with 98.9%-100% SVR, the SOF/DCV regimen had the greatest SVR rates (98.7%; 95% CI, 93.0%-100.0%) in genotype 3, and the OBV/PTV/R regimen was the best choice for genotype 4, with the highest SVR of 98.1% (95% CI, 94.4%-99.9%). In the pan-genotypic DAAs comparison, the G/P regimen showed the best pooled SVR of 99.4% (95% CI, 98.6%-100%). DAA regimens without Ribavirin or SOF showed the lowest rates of AEs (49.9%; 95% CI, 38.4%-61.5%) in HCV-infected ESRD patients.. The G/P could be recommended as the best option for the treatment of pan-genotypic HCV-infected ESRD patients. The OBV/PTV/R plus DSV, SOF/Velpatasvir (VEL), SOF/Ledipasvir (LDV), and SOF/DCV would be reliable alternatives for HCV treatment with comparable efficacy and safety profiles.. https://www.crd.york.ac.uk/prospero/#searchadvanced, PROSPERO: CRD42021242359.

Topics: Antiviral Agents; Bayes Theorem; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Kidney Failure, Chronic; Male; Network Meta-Analysis; Ritonavir; Treatment Outcome

We evaluated 8, 12, or 24 weeks of ledipasvir/sofosbuvir in patients with hepatitis C virus and end-stage renal disease undergoing dialysis.. Primary efficacy end point was sustained virologic response 12 weeks after treatment. Primary safety end point was treatment discontinuation because of adverse events (AEs).. Ninety-four percent (89/95) achieved sustained virologic response 12 weeks after treatment. Six patients died during treatment (n = 4) or before study completion (n = 2); no deaths were related to treatment. No patients discontinued treatment because of AEs. Thirteen percent had serious AEs; none were related to treatment.. Treatment with ledipasvir/sofosbuvir was safe and effective in patients with end-stage renal disease undergoing dialysis.

Topics: Adult; Aged; Aged, 80 and over; Antiviral Agents; Benzimidazoles; Drug Administration Schedule; Female; Fluorenes; Hepatitis C; Humans; Kidney Failure, Chronic; Male; Middle Aged; Sofosbuvir; Sustained Virologic Response; Treatment Outcome

Direct-acting antivirals (DAAs) play a key role in the eradication of hepatitis C virus (HCV) infection. However, limited data are available on DAA for treating HCV infection in hemodialysis (HD) patients. This study was to evaluate the pharmacokinetic characteristics and effectiveness of daclatasvir/sofosbuvir (DAC/SOF) and ledipasvir/SOF (LDV/SOF) in HD patients.. Seven patients were given SOF coadministered with DAC or LDV once daily for 12 weeks. The plasma concentrations of SOF007, DAC, and LDV were determined by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.. A sustained virologic response in week 12 (SVR12) was achieved in 6 (100%) patients, except for 1 patient dying due to severe cerebral hemorrhage not related to antiviral therapy. The extraction ratio of SOF007 was 66.67%, and the estimated HD clearance of SOF007 was 5.65 L/h.. The combination of SOF with either DAC or LDV is well tolerated and offers high SVR12 in HD patients.

Topics: Adult; Aged; Benzimidazoles; Carbamates; Clinical Trials as Topic; Drug Monitoring; Drug Therapy, Combination; Female; Fluorenes; Hepatitis C, Chronic; Humans; Imidazoles; Kidney Failure, Chronic; Male; Middle Aged; Pyrrolidines; Renal Dialysis; Sofosbuvir; Treatment Outcome; Valine

Hepatitis C virus (HCV) infection in end stage renal disease (ESRD) is associated with increased mortality. Recently, numerous directly acting antiviral agents have been approved for the management of HCV. Ledipasvir along with Sofosbuvir has been approved for management of genotype 1 infection in patients with eGFR ≥30 mL/min. However, there is paucity of data regarding its role in the management of patients on dialysis.. This is a single center prospective open label observational study to assess the safety and efficacy of Ledipasvir and Sofosbuvir in hemodialysis (HD) patients who were diagnosed with HCV genotype 1 infection. Eligibility criteria were treatment naive HD patients with normal liver histology. We administered Ledipasvir and Sofosbuvir combination tablet on alternate days for a period of 12 weeks. Primary efficacy end point was the assessment of sustained virological response (SVR12), and the safety end point was the discontinuation of therapy secondary to adverse drug effects.. A total of 21 patients were treated with this regimen. Two patients expired during the study period and are not related to the therapy. SVR12 was achieved in all the 19 patients. None of the patients in our study discontinued the therapy or had severe adverse drug effects. One patient had head ache and another patient had giddiness which were managed symptomatically.. Ledipasvir and Sofosbuvir combination therapy on alternate days, is effective even in ESRD patients, with excellent SVR12 rates, and it is as safe as in other population groups, without any major adverse reactions.

Topics: Adult; Aged; Antiviral Agents; Benzimidazoles; Female; Fluorenes; Hepacivirus; Hepatitis C, Chronic; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis; Sofosbuvir; Treatment Outcome; Young Adult

Topics: Antiviral Agents; Benzimidazoles; Disease Progression; Drug Administration Schedule; Drug Therapy, Combination; Fluorenes; Hepatitis C; Humans; Kidney Failure, Chronic; Renal Dialysis; Sofosbuvir

The availability of direct acting antiviral agents (DAA) has transformed the treatment of hepatitis C virus (HCV) infection. The current study is a case series that reports the outcomes from a cohort of twenty-five HCV-infected ESRD patients who received a kidney from an anti-HCV-positive deceased organ donor followed by treatment with DAAs in the early post-transplant period. Time to transplantation and the efficacy of DAA therapy as measured by sustained viral response at 12 weeks were assessed. The median waiting time from original date of activation on the United Network Organ Sharing (UNOS) waiting list until transplantation was 427 days; however, the median time from entering the patient into UNet

Topics: Adult; Aged; Antiviral Agents; Benzimidazoles; Carbamates; Donor Selection; Drug Therapy, Combination; Female; Fluorenes; Follow-Up Studies; Hepatitis C, Chronic; Humans; Imidazoles; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Postoperative Care; Pyrrolidines; Retrospective Studies; Ribavirin; Simeprevir; Sofosbuvir; Tissue Donors; Treatment Outcome; Valine

We report here the successful treatment of hepatitis C virus (HCV) transmitted from a nucleic acid testing (NAT)-negative donor to three HCV-negative recipients-two renal transplants and one liver. Both renal recipients underwent standard deceased-donor renal transplantation with immediate graft function. The liver recipient underwent standard orthotopic liver transplantation and recovered uneventfully. The donor was a 39-year-old woman with a terminal serum creatinine of 0.7 mg/dL. She was high risk for bloodborne pathogens, based upon a history of sexual contact with an HCV-infected male partner. Recipient 1 was a 45-year-old man with a history of end-stage renal disease from systemic lupus erythematosus. Recipient 2 was a 62-year-old woman with a history of end-stage renal disease caused by hypertension and insulin-dependent diabetes. Recipient 3 was a 42-year-old man with acute liver failure from acetaminophen ingestion. All recipients became HCV polymerase chain reaction positive on post-transplant follow-up. Both kidney recipients were treated with ledipasvir/sofosbuvir combination therapy for 12 weeks without side effects or rejection episodes. Recipient 3 was treated with ledipasvir/sofosbuvir in combination with ribavirin for 12 weeks without side effects. All patients achieved a sustained viral response at 12 weeks and are considered cured of HCV. The kidney recipients maintained good allograft function with a serum creatinine of 1.4 mg/dL and 1.0 mg/dL, respectively. Both renal recipients maintained normal liver function post treatment and did not develop any evidence of fibrosis. The liver recipient's liver function tests returned to normal without further incident. This case report provides evidence for the successful treatment of donor-derived HCV in transplant recipients.

Topics: Acetaminophen; Adult; Allografts; Antiviral Agents; Benzimidazoles; Blood-Borne Pathogens; Chemical and Drug Induced Liver Injury; Disease Transmission, Infectious; Drug Therapy, Combination; Female; Fluorenes; Hepacivirus; Hepatitis C; Humans; Kidney Failure, Chronic; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Polymerase Chain Reaction; Ribavirin; RNA, Viral; Sofosbuvir; Transplant Recipients; Viral Load

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.. 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).. 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.. 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.

Topics: Adult; Aged; Antiviral Agents; Benzimidazoles; Drug Therapy, Combination; Female; Fluorenes; Glomerular Filtration Rate; Hepacivirus; Hepatitis C, Chronic; Humans; Kidney Failure, Chronic; Male; Middle Aged; Ohio; Renal Dialysis; Simeprevir; Sofosbuvir; Sustained Virologic Response