P0475CRESCENTIC GLOMERULONEPHRITIS FOLLOWING HCV TREATMENT WITH DAAS, THE NON-CLASSIC TALE

Abstract

Abstract Background and Aims Observational studies suggest that acute kidney injury may occur in up to 15% of patients treated with sofosbuvir based regimens. Histological findings show features of acute interstitial nephritis (AIN) or acute tubular necrosis (ATN). Here, we report the first case of small vessel vasculitis following sofosbuvir treatment. Method A 65-year-old female with controlled T2DM was recently diagnosed with HCV. She attained sustained viral response (SVR) after a three-month course of (sofosbuvir + daclatasvir + ribavirin). Kidney functions were normal pre and post treatment. Three months later, she presented with puffiness, bilateral lower extremities edema (no rash) and vomiting. Labs showed acute kidney injury (AKI), nephrotic proteinuria and haematuria (table 1). Immunological investigations (C3, C4, ANA, ANCA and anti-GBM), paraproteinemia workup and cryoglobulins were all negative. Renal US was also normal. Kidney biopsy revealed focal necrotizing glomerulonephritis with 70% crescents (figure 3,4). No chronic changes were detected in the glomeruli, interstitium or tubules. The patient received pulse methylprednisolone 0.5 gm for 3 days followed by oral prednisolone 60 mg/day. Oral cyclophosphamide was initiated at 150 mg after biopsy result was obtained. Our patient showed clinical and laboratory improvement (figure 1,2), however, she developed bone marrow suppression that required cessation of cyclophosphamide. Valsartan initiated to control proteinuria with slight increase in serum creatinine to 1.4 mg/dl. The patient is still under close follow up every two weeks, with a plan to introduce rituximab if serum creatinine continued to increase. Results AKI following HCV treatment with DAA has been reported. Explanation includes AIN, ATN and cryoglobulinemic vasculitis (CV). AIN and ATN usually occur during the treatment course, which is not the case in our patient as she developed AKI three months following the end of the treatment, and the biopsy did not show signs of either ATN or AIN. New onset CV has been reported previously in 3 case reports following SVR after DAA treatment. Previous reports explained that HCV can induce B-cell clonal proliferation that may persist independent of viral eradication and produce IgM kappa which will result in cryoglobulinemic GN, again this is not true in our case. Our patient did not have a rash, her serum cryoglobulin was negative and complement levels (C3 and C4) were normal and biopsy did not show evidence of CV. As far as we know, this is the first case with suspected sofosbuvir associated small vessel vasculitis to be reported. Despite the patient had a negative serum ANCA levels, we suspect that this is a case of drug induced vasculitis. Drug induced vasculitis has been reported with hydralazine, propylthiouracil and cocaine, none of these drugs were used in our case. Also, there is no reported case of vasculitis associated with ribavirin or daclatasvir. Thus, we suspect Sofosbuvir is the cause of drug induced vasculitis in this patient. Conclusion Crescentic GN following HCV treatment using DAA is a serious complication that should be promptly diagnosed and managed. Physicians treating HCV infected patients should be aware of this possible complication and monitor for kidney function even after achieving SVR.