Sofosbuvir-based regimen is safe and effective for hepatitis C infected patients with stage 4–5 chronic kidney disease: a systematic review and meta-analysis

Abstract

BackgroundWhether sofosbuvir is suitable for hepatitis C virus (HCV) infected patients with severe renal impairment is inconclusive. This systematic review aims to evaluate the safety and effectiveness of SOF-based regimen in the setting of stage 4 and 5 chronic kidney disease (CKD).MethodsWe conducted a systematic literature search in PubMed, Web of Science, EMBASE and Google Scholar with searching strategy: (sofosbuvir OR Sovaldi OR Harvoni OR Epclusa OR Vosevi) AND (severe kidney impairment OR severe renal impairment OR end-stage renal disease OR dialysis OR renal failure OR ESRD OR renal insufficiency OR hepatorenal syndrome OR HRS). Sustained virological response (SVR12/24) rate and serious adverse event (SAE) rate with 95% confidence intervals were aggregated. Subgroup analysis was implemented to evaluate the impact of treatment strategy and patient characteristics.ResultsTwenty-one studies met inclusion criteria, totaling 717 HCV infected patients with CKD stage 4 or 5 (58.4% on dialysis). Pooled SVR12/24 was 97.1% (95% CI 93.9–99.3%), and SAE rate was 4.8% (95% CI 2.1–10.3%). There was no significant difference at SVR12/24 (97.1% vs 96.2%, p = 0.72) or SAE rate (8.8% vs 2.9%, p = 0.13) between subgroups applying full or decreased dose of sofosbuvir. Cirrhotic and non-cirrhotic patients achieved comparable sustained virological response (RR 0.93, 95% CI 0.85–1.02). Four studies reported eGFR/serum creatinine pre- and post- treatment, with no significant modification.ConclusionsOur study suggests SOF-based regimen might be used safely and effectively in patients living with HCV infection/stage 4–5 CKD, with normal and reduced dose of sofosbuvir. Prospective and well-controlled trials are needed to confirm these findings.Trial registrationPROSPERO CRD42018107440.Electronic supplementary materialThe online version of this article (10.1186/s12985-019-1140-x) contains supplementary material, which is available to authorized users.

Hematological Changes in HCV Patients Treated with Different Sofosbuvir-Based Regimens

“…This is near to what we found in ALLY-3 trial, where 152 treatment-naive and treatment-experienced subjects with HCV genotype 3 infection were treated with dclatasvir in combination with sofosbuvir [12]. The safety and beneficial effects of sofosbuvir not only confined to the combinations we used as with what reported with daclatasvir [13], but also reported in other combinations as with velpatasvir [14], and moreover this safety and beneficial effects have been found in special difficult to treat cases [15] . For patients suffering compensated chronic hepatitis C virus infection and received treatment by regimens containing sofosbuvir combined with interferon or ribavirin or both together, there was a significant decrease in the levels of hemoglobin, total leucocytic count and platelet count before and after treatment.…”

Efficacy and safety of sofosbuvir in the treatment of hep C among patients on hemodialysis: a systematic review and meta-analysis

“…Several large-scale studies evaluated the efficacy and safety among patients with HCV infection and severe renal impairment, treated with SOF-based regimens 8,9 . A longitudinal prospective study by Saxena et al compared outcomes of HCV infection between 1716 pts with estimated glomerular filtration rate (eGFR) > 45 ml/ min/1.73 m 2 to 73 patients with an eGFR ≤ 45, of which five were on hemodialysis.…”

“…Sofosbuvir (SOF)-based regimens are not recommended for patients requiring hemodialysis since renal clearance of SOF is the major elimination pathway, although since the recent U.S. Federal Drug Administration change in label, removing restrictions on its use in renal impairment, this will undoubtedly change 7 . Nevertheless, clinical studies provide evidence that use of SOF, among HCV positive patients with renal impairment, is effective and safe 8 , 9 . Data focusing only on patients requiring maintenance hemodialysis are limited.…”

Immediate administration of antiviral therapy after transplantation of hepatitis C-infected livers into uninfected recipients: Implications for therapeutic planning

“…At the time of trial initiation, the only available alternative pangenotypic DAA regimen was sofosbuvir based and had not yet been approved for use in patients with limited renal function. The safety of sofosbuvir‐based DAA regimens in patients with renal compromise has now been demonstrated, and given that these regimens have not been found to cause hepatotoxicity, we acknowledge that alongside GP, consideration should be given to use of sofosbuvir‐based regimens in patients experiencing delayed recovery of liver graft function.…”