Drugs that are primarily metabolised by the liver can be used in people with severe renal impairment and in those receiving haemodialysis; drugs excreted by the kidneys should be avoided or the dose regimen modified. As sofosbuvir is renally excreted and there are limited safety data on its use in people with severe renal impairment, it is not currently recommended for use in people with an eGFR < 30 mL/min/1.73 m2. This advice was based on pharmacokinetic studies of a single 400 mg dose of sofosbuvir that resulted in an increased area under the curve of 171% for sofosbuvir and 451% for its inactive metabolite (GS-331007), which is excreted exclusively by the kidneys, in people with an eGFR < 30 mL/min/1.73 m2. However, data showing the clinical safety of sofosbuvir-based regimens in patients with severe CKD are emerging. The US FDA has recently approved updated labelling for sofosbuvir-containing regimens, stating that no dosage adjustment is recommended for patients with any degree of renal impairment, including patients requiring dialysis. An update to the Australian product information is anticipated.
Glecaprevir and pibrentasvir are cleared by hepatic metabolism, and this is now a preferred treatment regimen for people with severe renal impairment. The efficacy of this pan-genotypic regimen was evaluated in 104 patients with Gt 1–6 HCV infection enrolled in a Phase III study.  All patients had severe renal impairment (eGFR < 30 mL/min/1.73 m2) or were dependent on dialysis. The SVR rate was 98% (102/104). No virological failures were observed. Adverse events were common, and 24% of patients experienced at least one serious adverse event. High rates of adverse events, including serious adverse events, are common in people with severe renal impairment.
Elbasvir and grazoprevir are also cleared by hepatic metabolism and can be used in people with severe renal impairment. This was the first regimen to be evaluated in a large Phase III study enrolling people with severe renal impairment. Its efficacy in people with chronic kidney disease (eGFR < 30 mL/min/1.73 m2, with or without haemodialysis requirements) was evaluated in a large Phase III randomised study in which 224 people with chronic Gt 1 HCV infection were randomly assigned to immediate or deferred therapy with elbasvir and grazoprevir.  The deferred treatment arm provided a placebo comparator to the immediate treatment arm. Ribavirin was not used, despite 52% of the cohort being infected with Gt 1a HCV. In the immediate treatment arm, the SVR rate was 94.3% in the full analysis set. The SVR rate was 99.1% in a modified analysis set that excluded patients who discontinued treatment for reasons that were not related to virological failure. Adverse events were frequent in this population with significant comorbidities but were comparable between the immediate and deferred treatment groups (76% v 84%). People with Gt 1a or Gt 1b HCV, as well as those with Gt 4 HCV infection, who have severe renal impairment (eGFR < 30 mL/min/1.73 m2) or end-stage renal disease, including patients receiving dialysis, should be treated with elbasvir plus grazoprevir without ribavirin. 
As noted above, severe renal impairment necessitates a significant dose reduction for ribavirin. Ribavirin should only be used in this setting under the supervision of a specialist with experience in treating HCV infection in people with severe renal impairment.