A potential novel use for direct antiviral therapy

A 60-year-old male with a history of hepatitis C virus (HCV) infection, hypertension, and previous stroke presented for evaluation of increasing abdominal girth, lower extremity swelling, and increased confusion over the past 2 months. On physical examination, he had minimal ascites and bilateral pitting lower extremity edema. He was confused, scoring an 8 of 30 on the Montreal Cognitive Assessment, and had left-sided residual weakness from his previous stroke, but no other focal neurologic deficits, including no asterixis. Laboratory data on admission included a creatinine of 1.6 mg/dL (baseline, 1.0 mg/dL), and urinalysis showed proteinuria (greater than 1,000 mg/dL) and hematuria (336 red blood cells per high-field power). He had a witnessed seizure shortly after admission, which was evaluated with a magnetic resonance imaging, revealing multiple embolic infarcts (Fig. 1). He was subsequently found to have a cryoglobulin level of 5%, rheumatoid factor of 2,860 IU/mL, and C3/C4 complement levels of 55 and 2 mg/dL, respectively. His 24-hour urine collection had 12 g of protein with a positive M-spike. He was diagnosed with cerebral vasculitis resulting in acute microembolic strokes as well as cryoglobulin-related glomerulonephritis. He received eight sessions of plasma exchange and was started on concurrent telaprevir-based therapy for his HCV. After 2 weeks of therapy, his HCV viral load decreased from 2.9 million to 4,544 IU/mL, his cryoglobulin level decreased to 1%, and his rheumatoid factor decreased to 430 IU/mL. During this same time period, he had significant improvement in his mental status and was back at his baseline 1 month postdischarge. Treatment with telaprevir-based therapy was continued for 12 weeks, at which time his viral load was 775 IU/mL. Four weeks after discontinuation of his telaprevir, he experienced viral breakthrough, and his most recent viral load is 3.3 million IU/mL. (A) Cerebral vasculitis and emboli (arrow) secondary to HCV-related cryoglobulinemia. (B) Cerebral vasculitis resulting in acute microembolic stroke (arrow). HCV is a leading cause of decompensated cirrhosis and liver-related mortality in the United States.1 Approximately 40% of patients with HCV have extrahepatic manifestations, including the potential for mixed cryoglobulinemia or cerebral vasculitis.2 Treatment of acute cryoglobulinemia is primarily limited to those with severe disease and includes immunosuppressive medications (e.g. corticosteroids, and/or plasmapharesis). HCV treatment has demonstrated efficacy in patients with HCV-associated cyroglobulinemia and is recommended for long-term management.3 Pegylated IFN (Peg-IFN) and ribavirin (RBV) can achieve initial virologic response rates as high as 63% in patients with mild to moderate HCV-related cyroglobulinemia, but has been limited by low rates of sustained virologic response.3 In patients with severe disease, an induction phase of immunosuppresion has traditionally been regarded as first-line therapy, and Peg-IFN and RBV are traditionally started electively as an outpatient given the slow decline in viral load. The recent introduction of direct-acting antivirals, including telaprevir, currently allows for more-rapid reduction in HCV viral loads.4 In this case, we postulated that rapid virologic clearance would benefit our patient. Because our patient was treated with a combination of plasma exchange and telaprevir-based therapy concurrently, we are unable to determine the degree of clinical improvement attributable to HCV therapy alone. However, we were able to demonstrate a rapid decline in his HCV viral load over the first 2 weeks of therapy. We believe that the use of telapravir to acutely reduce HCV viral load and decrease the formation of immunoprecipitates in acute severe cryoglobulinemia was helpful for our patient and may represent a novel use for direct antiviral therapy. Emre Turer, M.D., Ph.D.1 Don C. Rockey, M.D.1 Amit G. Singal, M.D., M.S.1,2 1Department of Medicine Division of Gastroenterology University of Texas Southwestern Medical Center and Parkland Hospital Dallas, TX 2Department of Clinical Sciences University of Texas Southwestern Dallas, TX HCV, hepatitis C virus; Peg-IFN; pegylated interferon; RBV, ribavirin.

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