New and Emerging Evidence on the Use of Second-Generation Direct Acting Antivirals for the Treatment of Hepatitis C Virus in Renal Impairment

2016 ◽  
Vol 30 (3) ◽  
pp. 359-365 ◽  
Author(s):  
Maria A. Sorbera ◽  
Michelle L. Friedman ◽  
Rebecca Cope
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Kidney Disease ◽  
Renal Impairment ◽  
Second Generation ◽  
Severe Renal Impairment ◽  
Treatment Options ◽  
Uncertain Data ◽  
Treatment Regimens ◽  
Direct Acting

Due to the intimate relationship between liver and kidney disease in hepatitis C virus (HCV) infection, treatment options for HCV-positive patients at any stage of chronic kidney disease (CKD) are essential. The availability of second-generation, direct-acting antiviral (DAA) combinations has allowed for the advent of interferon-sparing treatment regimens with shorter durations and minimal side effects. While many of the second-generation DAAs are principally metabolized by the hepatic system, dosing in severe renal impairment (creatinine clearance [CrCl] <30 mL/min) or dialysis has remained questionable due to limited experience. New evidence regarding the use of these agents in renal impairment continues to become available, as real-world experience with these treatment regimens is reported. Simeprevir, ledipasvir, paritaprevir, ombitasvir, dasabuvir, and daclatasvir have data to suggest safety in end-stage renal disease. While safety and efficacy with sofosbuvir remains uncertain, data are now available to support utilizing a dose adjustment when glomerular filtration rates are <30 mL/min. Upcoming regimens grazoprevir/elbasvir and daclatasvir/asunaprevir/beclavubir may provide further options for patients with advanced kidney disease, and ongoing studies will continue to provide guidance for this unique patient population. This article will review the currently available literature, including the newest emerging evidence, on the use of second-generation DAAs in CKD stages 3 to 5 and dialysis.

scholarly journals Safety and efficacy of sofosbuvir based regimen in the treatment of hepatitis C virus infection among hemodialysis patients in Morocco

2021 ◽  
Vol 5 (3) ◽  
pp. 077-080
Author(s):  
Tamzaourte Mouna ◽  
Zajjari Yassir ◽  
Berrag Sanae ◽  
Adioui Tarik ◽  
Aourarh Aziz ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Side Effects ◽  
Treatment Options ◽  
Hemodialysis Patients ◽  
Direct Acting Antiviral ◽  
Treatment Regimens ◽  
Patient Reported ◽  
Chronic Hcv ◽  
Direct Acting

The introduction of a new class of drugs known as direct acting antiviral (DAA) agents represents a revolution in the treatment of hepatitis C virus (HCV) in the general population, as these regimens are associated with higher sustained virological response (SVR) rates and fewer side effects. However, for patients with advanced chronic kidney disease suffering from HVC infection, treatment options including DAA remain limited. The aim of this study is to report our experience on Sofosbuvir (SOF) based regimen in the treatment of HCV in hemodialysis patients. In this observational study, we included all patients with chronic HCV infection on hemodialysis who were treated with SOF in our Hospital between April 2016 and March 2018. All patients were treated with a combination of 400 mg of SOF three times a week after hemodialysis and of 60 mg of Daclatasvir daily for a total of 12 to 24 weeks. A total of 20 hemodialysis patients were included in this study. 12 were females and the mean age was 52.1 ± 15.5 years. 11 patients were infected with HCV genotypes 1b. All patients achieved SVR. Clinical and biological tolerance was very good for all patients and none of them had to discontinue treatment because of side effects or developed hepatobiliary and cardiac toxicity. Two patients reported fatigue and another patient reported headaches. However, these symptoms were spontaneously resolved after the end of the treatment. In Morocco, despite the absence of new DAA combination treatment regimens which are not renally eliminated, our study concludes that SOF based treatment without Ribavirin or Peginterferon was effective and safe with minimal side effects. However, larger studies are still needed in order to validate these results.

scholarly journals Hepatocellular Carcinoma Risk According to Regimens for Eradication of Hepatitis C Virus; Interferon or Direct Acting Antivirals

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3414
Author(s):  
Hye Won Lee ◽  
Dai Hoon Han ◽  
Hye Jung Shin ◽  
Jae Seung Lee ◽  
Seung Up Kim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Pegylated Interferon ◽  
Direct Acting Antivirals ◽  
Treatment Regimens ◽  
Direct Acting ◽  
Similar Risk ◽  
Carcinoma Risk

By pegylated interferon (PegIFN)-free direct-acting antivirals (DAAs) against hepatitis C virus (HCV) infection, a sustained virological response (SVR) rate >95% can be attained with a satisfactory tolerability and shorter treatment duration. However, it remains controversial whether there is any difference in prognosis depending on regimens—PegIFN or DAAs. We compared the probabilities of hepatocellular carcinoma (HCC) development between patients achieving an SVR by PegIFN/ribavirin (PegIFN group, n = 603) and DAAs (DAAs group, n = 479). The DAAs group was significantly older and had a higher proportion of cirrhosis than the PegIFN group. Before adjustment, the DAAs group had a higher HCC incidence than the PegIFN group (p < 0.001). However, by multivariate analyses, the DAAs (vs. PegIFN) group was not associated with HCC risk (adjusted hazard ratio 0.968, 95% confidence interval 0.380–2.468; p = 0.946). Old age, male, higher body mass index, cirrhosis, and lower platelet count were associated with increased HCC risk (all p < 0.05). After propensity score matching (PSM), a similar HCC risk between the two groups was observed (p = 0.372). We also compared HCC incidences according to sofosbuvir (SOF)-based and SOF-free DAAs, showing a similar risk in both groups before adjustment (p = 0.478) and after PSM (p = 0.855). In conclusion, post-SVR HCC risks were comparable according to treatment regimens; PegIFN- vs. DAA-based regimens and SOF-based vs. SOF-free DAA regimens. Further studies with a longer follow-up period are required.

scholarly journals Effects of Renal Impairment and Hemodialysis on the Pharmacokinetics and Safety of the Glecaprevir and Pibrentasvir Combination in Hepatitis C Virus-Negative Subjects

2017 ◽  
Vol 62 (3) ◽  
Author(s):  
Matthew P. Kosloski ◽  
Weihan Zhao ◽  
Thomas C. Marbury ◽  
Richard A. Preston ◽  
Michael G. Collins ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Kidney Disease ◽  
Renal Impairment ◽  
Combined Treatment ◽  
Hcv Infection ◽  
Renal Elimination ◽  
Genotype 2

ABSTRACT Hepatitis C virus (HCV) infection is an independent risk factor for developing chronic renal impairment and end-stage renal disease. Limited treatment options are available for HCV genotype 2, 3, 5, and 6 infections in patients with an estimated glomerular filtration rate (eGFR) of <30 ml/min. Glecaprevir and pibrentasvir are active against all six major HCV genotypes, are primarily excreted in the bile, and have minimal renal elimination. Therefore, combined treatment with these direct-acting antivirals may be useful for patients with HCV infection and chronic kidney disease. A phase 1, multicenter, open-label study evaluated the effects of renal impairment on the pharmacokinetics and safety of glecaprevir-pibrentasvir. In substudy 1, 38 subjects with stage 2 to 5 chronic kidney disease who were not on dialysis or who had normal renal function received single doses of the combination of 300 mg glecaprevir and 120 mg pibrentasvir. In substudy 2, 8 subjects requiring hemodialysis received single doses of the combination of 300 mg glecaprevir and 120 mg pibrentasvir under dialysis and nondialysis conditions. Regression analyses demonstrated increased glecaprevir and pibrentasvir plasma exposures, as determined by the area under the curve, with decreasing renal function, up to 56% and 46%, respectively, in subjects with an eGFR of <15 ml/min/1.73 m 2 . In dialysis-dependent subjects, glecaprevir and pibrentasvir exposures were similar (≤18% difference) when study drugs were administered before hemodialysis or on a nondialysis day. Adverse events were mostly mild, with the most common being self-limited fatigue (3 subjects). The study findings support the clinical evaluation of glecaprevir-pibrentasvir without dose adjustment in HCV-infected subjects with renal impairment. (This study has been registered at ClinicalTrials.gov under registration number NCT02442258.)

Glecaprevir/pibrentasvir for patients with chronic hepatitis C virus infection and severe renal impairment

2020 ◽  
Vol 27 (6) ◽  
pp. 568-575 ◽  
Author(s):  
Chen‐Hua Liu ◽  
Sheng‐Shun Yang ◽  
Cheng‐Yuan Peng ◽  
Woan‐Tyy Lin ◽  
Chun‐Jen Liu ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Renal Impairment ◽  
Chronic Hepatitis C ◽  
Severe Renal Impairment ◽  
Hepatitis C Virus Infection ◽  
Chronic Hepatitis C Virus

Direct-acting Antivirals for Hepatitis C Virus in Patients on Maintenance Dialysis

2017 ◽  
Vol 40 (10) ◽  
pp. 531-541 ◽  
Author(s):  
Fabrizio Fabrizi ◽  
Francesca M. Donato ◽  
Piergiorgio Messa
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Severe Renal Impairment ◽  
Controlled Trial ◽  
Hcv Infection ◽  
Direct Acting Antivirals ◽  
Safety And Efficacy ◽  
Maintenance Dialysis ◽  
Chronic Hcv ◽  
Direct Acting

The frequency of hepatitis C virus (HCV) infection remains high in patients with chronic kidney disease (CKD) and plays a detrimental role in mortality in this population. According to the latest survey, the adjusted hazard ratio for HCV-positive versus HCV-negative patients on long-term dialysis was 1.12 (95% CI, 1.05 to 1.20) and 1.10 (95% CI, 0.98 to 1.22) for all-cause and cardiovascular mortality, respectively. An impairment on quality of life has also been documented in HCV-infected patients undergoing regular dialysis. Most clinicians have been so far reluctant to treat hepatitis C in patients with advanced CKD, due to concerns regarding low efficacy and safety of interferon-based regimens. The advent of all-oral, direct-acting antivirals (DAAs) has revolutionized treatment paradigms for HCV, including patients with other comorbidities such as CKD. Two combinations of DAAs have been recently approved for the treatment of HCV in advanced CKD: elbasvir/grazoprevir (evaluated in 1 randomized controlled trial) and ombitasvir/paritaprevir/ritonavir/dasabuvir with or without ribavirin (examined in some observational, single-arm studies). These antiviral combinations have provided high safety and efficacy (SVR12 rates >90%) in HCV-infected patients with stage 4–5 CKD. Sofosbuvir, a nucleotide analogue inhibitor of the HCV NS5B polymerase, is the cornerstone of most anti-HCV current regimens but is not currently recommended for patients with severe renal insufficiency (eGFR <30 mL/min per 1.73 m2). However, several small-sized studies have been published on the safety and efficacy of sofosbuvir-based regimens for patients with hepatitis C on maintenance dialysis>; overall, the viral response was satisfactory (SVR12 rates ranging between 58% and 100%) with a few drug-related drop-outs. Studies are in progress to assess whether ribavirin-free antiviral combinations with novel DAAs are a viable option for patients with severe renal impairment and chronic HCV infection.

scholarly journals The Efficacy and Safety of Sofosbuvir/Daclatasvir Fixed-Dose Combination in Iranian Hemodialysis Patients with Hepatitis C Virus Infection

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Kasra Ghanaat ◽  
Heidar Sharafi ◽  
Seyed Moayed Alavian
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Renal Impairment ◽  
Severe Renal Impairment ◽  
Hemodialysis Patients ◽  
Virologic Response ◽  
Hcv Infection ◽  
Fixed Dose ◽  
Efficacy And Safety ◽  
Patient Reported

Background: Although several regimens have been approved for the treatment of hepatitis C virus (HCV) infection, sofosbuvir-based regimens are not approved for the treatment of HCV infection in patients with severe renal impairment. Methods: This study was conducted on 51 hemodialysis patients infected with HCV. The patients received a constant dose of sofosbuvir/daclatasvir (SOF/DCV). Sustained virologic response (SVR) was evaluated 12 weeks after completion of treatment. The subjects were selected and treated with a combination of SOF/DCV. Eleven patients expired during the anti-HCV treatment due to causes not related to liver disease or antiviral therapy. Results: Finally, 40 patients finished the treatment, and 36 cases were evaluated for SVR. Among those tested for SVR, 35 (97.2%, 95% CI: 85.5 - 99.9%) achieved SVR and one (2.8%, 95% CI: 0.1 - 14.5%) relapsed. No patient reported severe adverse events. Conclusions: The combination of SOF/DCV showed great efficacy and safety in hemodialysis patients with severe renal impairment and chronic HCV infection.

scholarly journals Comorbidities and concomitant medications in patients with chronic hepatitis C virus infection receiving second-generation direct-acting antiviral regimens in Belgium : an observational study

2021 ◽  
Vol 84 (1) ◽  
pp. 33-41
Author(s):  
S Bourgeois ◽  
JP Mulkay ◽  
M Cool ◽  
X Verhelst ◽  
G Robaeys ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Concomitant Medication ◽  
Second Generation ◽  
Treatment Initiation ◽  
Primary Objective ◽  
Hcv Infection ◽  
Direct Acting Antiviral ◽  
Concomitant Medications ◽  
Direct Acting

Objective : To describe comorbidities and concomitant medications in patients initiating treatment for hepatitis C virus (HCV) infection with direct-acting antiviral (DAA) regimens in Belgium. Methods : This was a noninterventional, observational, multi-center study of data from patient charts. Adult patients with HCV infection receiving second-generation DAA therapy were included. Comorbidities were assessed at the time of HCV treatment initiation. Concomitant medications were recorded at the time of diagnosis and at treatment initiation. Potential clinically relevant drug-drug interactions (DDIs) were assessed based on information available at www.hep-druginteractions.org.The primary objective was to describe concomitant medication use ; secondary objectives were to describe modifications in concomitant therapies and comorbidities. Results : 405 patients were included. A total of 956 comorbidities were reported by 362 patients (median, 2 ; range, 0-15). The most common comorbidities were hypertension (27.2%) ; HIV coinfection (22.5%), and type 2 diabetes mellitus (14.3%). Overall, 1455 concomitant medications were being taken by 365 patients (90.1% ; median, 3 ; range 0-16). The most common concomitant medications were psycholeptics (28.6%), antiviral agents (24.2%), and medications for acid-related disorders (21.0%) Overall, 74/365 (20.3%) patients receiving a concomitant medication required an adaptation to their concomitant medication. The medications that most frequently required change were drugs for acid-related disorders (n = 14) and antiviral drugs (n = 5) ; those that were most frequently stopped were lipid-modifying drugs (n = 25) and drugs for acid-related disorders (n = 13). Conclusion : Physicians are aware of the potential for DDIs with DAAs, but improved alignment between clinical practice and theoretical recommendations is required. (Acta gastroenterol. belg., 2021, 84, 33-41).

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