Ledipasvir/Sofosbuvir in the Treatment of Hepatitis C Virus Genotype 6

Abstract

Chronic hepatitis C virus (HCV) is the leading cause of liver cirrhosis and the primary reason for liver transplant referral in the United States (US). In the US, most HCV infections are due to HCV genotype 1 (HCV-1), which was traditionally treated with 48 weeks of pegylated interferon (IFN) and ribavirin with a cure rate of approximately 40% and substantial treatment-related toxicity. Recently, the IFN-free single tablet regimen of ledipasvir/sofosbuvir (LDV/SOF) was approved for HCV-1 infection with cure rate >90%. The utility of LDV/SOF in less common genotypes, such as HCV genotype 6 (HCV-6), is unknown. The standard of care for patients with HCV-6 continues to be pegylated-IFN and ribavirin. Herein, we report a case of HCV-6 successfully treated with LDV/SOF. A 34-year-old Vietnamese-American woman who acquired HCV-6 through vertical transmission was found to have stage 2 fibrosis on liver biopsy. In 2010, she was treated with pegylated-IFN and ribavirin; however, therapy was discontinued at week 4 due to non-response. With the availability of direct-acting antiviral (DAA) agents she was considered for retreatment in 2014. At that time, she was asymptomatic, lab work revealed total bilirubin 0.3 mg/dL, alkaline phosphatase 41 IU/L, alanine transaminase (ALT) 133 IU/L, aspartate transaminase (AST) 75 IU/L, total protein 7.6 g/dL, albumin 4.2 g/dL, and HCV viral load (VL) 846,636 IU. She was treated off-label with 12 weeks of once-daily LDV/SOF after informed consent. By week 2, her VL was detectable, but below the limit of quantitation (< 15 IU), and her ALT and AST normalized to 32 IU/L and 24 IU/L, respectively. At treatment weeks 4 and 8, her VL was undetectable and all biochemical and hematologic parameters were normal. She had no reported treatment side effects. Off treatment VL at weeks 4 and 12 were undetectable, consistent with sustained virologic response (SVR). HCV-6 is endemic to Southeast Asia; however, in the US, is primarily found in Asian immigrants. Thus, it is important to be aware of potential treatment options for HCV-6 as the US population of Asian immigrants grows. Since IFN based therapy, with associated treatment toxicity and low cure rates, remains the standard of care for HCV-6, there exists a major unmet need to bring safer and more efficacious options to this HCV population. Here, we report the successful cure of HCV-6 with 12 weeks of LDV/SOF. With new DAA agents available, the treatment of HCV-6 is rapidly evolving.