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

Abstract

Hepatitis C virus (HCV) infection among maintenance hemodialysis patients is implicated in increased morbidity and mortality compared to uninfected patients. Sofosbuvir (SOF)-based regimens may not be optimal among patients requiring hemodialysis. Several studies, however, provide evidence that use of SOF among HCV-positive patients with renal impairment, is effective and safe. We searched Pubmed and Embase to identify studies reporting the efficacy and safety of SOF-based regimens for the treatment of HCV-positive patients on maintenance hemodialysis and performed a random effects meta-analysis. The overall pooled estimate of the efficacy of SOF-based therapy was 95% (95% CI 91-98%). The efficacy of the SOF-based regimen was 92% (95% CI 80-99%), 98% (95% CI 96-100%), and 100% (95% CI 95-100%) for the following doses: 400 mg on alternate days, 400 mg daily, and 200 mg daily, respectively. The most frequent adverse event was fatigue with a pooled prevalence of 16% (95% CI 5-29%), followed by anemia 15% (95% CI 3-31%), and nausea or vomiting 14% (95% CI 4-27%). Anemia was more prevalent in treatment regimens containing ribavirin (46%, 95% CI 33-59%) compared to ribavirin-free regimens (3%, 95% CI 0-9%). This study suggests that SOF-based regimens in the treatment of HCV infection among hemodialysis patients are both effective and safe. Patients requiring hemodialysis are at an increased risk of acquiring hepatitis C virus (HCV) 1. Approximately 5% of patients on hemodialysis are diagnosed with HCV, compared to 1% in the United States population 2,3 and, among hemodialysis patients, HCV infection is associated with poor outcomes with substantially higher rates of hepatic-related mortality and hospitalizations, and lower health-related quality of life scores, compared to HCV negative hemodialysis patients 4. National guidelines for the treatment of HCV infection among hemodialysis patients recommend several direct-acting antivirals (DAA) 5,6. 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. Thus, we performed a systematic review and meta-analysis to quantify the efficacy and safety of SOF-based regimens among the subset of patients with severe renal impairment that required maintenance hemodialysis.

An updated systematic review and meta-analysis on efficacy of Sofosbuvir in treating hepatitis C-infected patients with advanced chronic kidney disease

“…The pooled incidence of SAE due to SOF-based regimen in our study was 11%, which was similar to the study by Li T et al, in which the pooled SAE rate for DAA-based antiviral therapies in HCV/Stage 4-5 CKD patients was 12.1% [51]. Shehadeh et al also reported a 10% incidence for SAE, which is quite similar to our results [20].…”

“…In a recent systematic review, the safety and efficacy of Sofosbuvir was explored among patients on HD [20] and results are quite similar to the results of the current study. However, there is a very important difference between the two studies.…”

“…Li M et al (2019) also suggested lower dose of SOF as routine or usage of half dose once every 2 days with the same efficacy [50]. Shehadeh et al also showed higher efficacy with low-dose treatment [20].…”

Effectiveness of Sofosbuvir and Velpatasvir Combination in Chronic Hepatitis C with Hemodialysis Patients

“…Our findings were comparable to the previous some studies. [13,14] We found that hypertension was the most common comorbidity found in 15 (55.55%) patients followed by obesity 8 (29.63%) and diabetes found in 3 (14.81%). [15] Among 27 cases 20 (74.04%) were naïve and 7 (25.96%) were treatment experienced.…”

“…[15] Among 27 cases 20 (74.04%) were naïve and 7 (25.96%) were treatment experienced. [13,14] Sustained virological response was found in 26 (96.3%) and 1 (3.7%) patients were lost at follow up. In 15 patients who were treated with SOF of 200 mg vs. 400 mg alternate day, the figure in Bhamidimarri et al [16] was 91% vs75% SVR12.…”