Treatment of HCV in people with renal impairment

Management of hepatitis C in patients with renal impairment is possible. No dose adjustment is required for the current first-line DAA regimens of sofosbuvir plus velpatasvir, glecaprevir plus pibrentasvir, and sofosbuvir plus velpatasvir plus voxilaprevir. Patients with severe renal impairment (eGFR < 30 mL/min/1.73 m2 or haemodialysis) should be in specialist care, involving both a nephrologist and a clinician experienced in the treatment of hepatitis C.

Glecaprevir, pibrentasvir, velpatasvir and voxilaprevir are not renally excreted. Sofosbuvir is renally excreted; however, no dose adjustment for sofosbuvir-containing regimens is required for patients with renal impairment, including those with ESRD requiring dialysis.[109-113] Safety data remain limited for patients with severe renal impairment (eGFR < 30 mL/min/1.73 m2) and ESRD who are not receiving haemodialysis and are being treated with sofosbuvir.

Ribavirin is rarely used in the treatment of hepatitis C but is renally excreted and cannot be removed by dialysis. Ribavirin accumulates in the setting of renal impairment with creatinine clearance < 50 mL/min and can cause severe anaemia.[114] The product information recommends that ribavirin should not be used in individuals with an eGFR < 50 mL/min/1.73 m2. In specialist centres, ribavirin-containing regimens may be considered for those with an eGFR < 50 mL/min/1.73 m2. In this setting, ribavirin therapy should be started at a low dose, with close monitoring of haemoglobin levels. Recommended ribavirin dose according to eGFR is: > 50 mL/min/1.73 m2, no dose adjustment; 30–50 mL/min/1.73 m2, alternating doses of 200 mg and 400 mg every other day; < 30 mL/min/1.73 m2, 200 mg daily; haemodialysis, 200 mg pre-dialysis.

Treatment of people with hepatitis C and renal impairment is very effective. The efficacy of glecaprevir plus pibrentasvir in people with severe renal impairment was prospectively evaluated in 104 patients with Gt 1–6 HCV infection enrolled in a Phase III study.[115] All patients had an 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. Glecaprevir plus pibrentasvir is a preferred regimen for treating hepatitis C in people with severe renal impairment.

Hepatitis C may rarely be associated with intrinsic renal disease, including cryoglobulinaemia and glomerulonephritis.116 People with renal impairment should be investigated to determine the underlying cause and managed appropriately. Those with severe acute vasculitic manifestations may require immunosuppressive therapy, including anti-CD20 antibody therapy and/or plasma exchange (note that any patient with HCV who is treated with B cell-depleting therapy must be screened for HBV infection, and patients who have been exposed to HBV will require antiviral therapy to prevent HBV reactivation). In addition, the prevalence of anti-HCV antibodies is higher in patients requiring haemodialysis compared with the general population.