Sofosbuvir Given the Green Light
Compared with the 2018 guideline, which recommended against sofosbuvir in patients with CKD G4 and G5, including those on dialysis, because of concerns about metabolization via the kidneys, the new guideline suggests that sofosbuvir-based DAA regimens are appropriate in patients with glomerular filtration rate (GFR) less than 30 mL/min per 1.73 m2, including those receiving dialysis.
This recommendation was based on a systematic review of 106 studies including both sofosbuvir-based and non-sofosbuvir-based DAA regimens that showed high safety and efficacy for all DAA regimen types across a broad variety of patient types.
“DAAs are highly effective and well tolerated treatments for hepatitis C in patients across all stages of CKD, including those undergoing dialysis and kidney transplant recipients, with no need for dose adjustment,” Dr. Awan and colleagues wrote.
Loosened Biopsy Requirements
Unlike the 2018 guideline, which advised kidney biopsy in HCV-positive patients with clinical evidence of glomerular disease prior to initiating DAA treatment, the new guideline suggests that HCV-infected patients with a typical presentation of immune-complex proliferative glomerulonephritis do not require confirmatory kidney biopsy.
“Because almost all patients with chronic hepatitis C (with or without glomerulonephritis) should be treated with DAAs, a kidney biopsy is unlikely to change management in most patients with hepatitis C and clinical glomerulonephritis,” the panelists wrote.
If kidney disease does not stabilize or improve with achievement of sustained virologic response, or if there is evidence of rapidly progressive glomerulonephritis, then a kidney biopsy should be considered before beginning immunosuppressive therapy, according to the guideline, which includes a flow chart to guide clinicians through this decision-making process.
Individualizing Immunosuppressive Therapy
Consistent with the old guideline, the new guideline recommends DAA treatment with concurrent immunosuppressive therapy for patients with cryoglobulinemic flare or rapidly progressive kidney failure. But in contrast, the new guideline calls for an individualized approach to immunosuppression in patients with nephrotic syndrome.
Dr. Awan and colleagues suggested that “nephrotic-range proteinuria (greater than 3.5 g/d) alone does not warrant use of immunosuppressive treatment because such patients can achieve remission of proteinuria after treatment with DAAs.” Still, if other associated complications — such as anasarca, thromboembolic disease, or severe hypoalbuminemia — are present, then immunosuppressive therapy may be warranted, with rituximab remaining the preferred first-line agent.
More Work Is Needed
Dr. Awan and colleagues concluded the guideline by highlighting areas of unmet need, and how filling these knowledge gaps could lead to additional guideline updates.
“Future studies of kidney donations from HCV-positive donors to HCV-negative recipients are needed to refine and clarify the timing of initiation and duration of DAA therapy and to assess long-term outcomes associated with this practice,” they wrote. “Also, randomized controlled trials are needed to determine which patients with HCV-associated kidney disease can be treated with DAA therapy alone versus in combination with immunosuppression and plasma exchange. KDIGO will assess the currency of its recommendations and the need to update them in the next 3 years.”
The guideline was funded by KDIGO. The investigators disclosed relationships with GSK, Gilead, Intercept, Novo Nordisk, and others. Dr. Rastogi and Dr. Debes had no conflicts of interest.