Combination ledipasvir-sofosbuvir for the treatment of chronic hepatitis C virus infection: a review and clinical perspective

Abstract

Chronic hepatitis C treatment has continued to evolve, and interferon-free, oral treatment with direct-acting antiviral agents is the current standard of care. Recently, a new treatment, which is a combination of two direct-acting antiviral agents, ledipasvir 90 mg (anti-NS5A) and sofosbuvir 400 mg (anti-NS5B), has been approved in the US and the European Union for the treatment of chronic hepatitis C viral infection. In Phase III trials among chronic hepatitis C virus genotype 1 monoinfected (treatment-naïve, treatment-experienced, and with advanced liver disease or posttransplant) patients and HIV–hepatitis C virus coinfected patients, the ledipasvir-sofosbuvir fixed-dose combination is associated with a higher rate of sustained virologic response at 12 weeks after therapy has ceased. According to preliminary data, the ledipasvir-sofosbuvir combination also may be effective against hepatitis C genotype 4 virus infection. The ledipasvir-sofosbuvir combination taken orally is generally well-tolerated. Moreover, the combination treatment may suppress the effect of predictive factors of chronic hepatitis C that have historically been known to be associated with treatment failure. Thus, the fixed-dose single-tablet combination of ledipasvir-sofosbuvir offers a new era for the effective treatment of a variety of patients suffering from chronic hepatitis C virus infection.

Ledipasvir/sofosbuvir for treatment of hepatitis C virus in sofosbuvir‐experienced, NS5A treatment‐naïve patients: Findings from two randomized trials

“…Two of the relapsed participants had confirmed NS5A RAS at baseline, however, all 10 had emergent mutations at position 30 and/or 93. The NS5A RAS observed in these studies have previously been attributed to reduced efficacy of LDV in vitro and detected at treatment failure in phase III studies . No emergent NS5B RAS were observed in any of the relapsed participants.…”

Post Hepatitis C Cirrhosis in Sub-Sahara Kidney Transplant, Treated with Sofosbuvir/Ledipasvir: Report of Case and Review of Literature

“…There are no major studies evaluating the combination Sofosbuvir/Ledipasvir in HCV infected patients with HCV genotype 2 and Ledipasvir has a low activity on HCV genotype [12]. We did not find in the literature a study evaluating the combination sofosbuvir/ledipasvir in kidney transplant patients infected with HCV genotype 2.…”

Eltrombopag enables initiation and completion of pegylated interferon/ribavirin therapy in Japanese HCV‑infected patients with chronic liver disease and thrombocytopenia

“…Furthermore, the long-term effects of DAAs remain unclear. Certain DAAs have been associated with the worsening of dyslipidemia (6,7). Although some recent reports have suggested that an SVR by DAA therapy reduces the risk of developing hepatocellular carcinoma (HCC), the role of DAAs in the recurrence of HCC in patients treated for hepatic decompensation remains controversial, and thus, warrants further elucidation and follow-up in the HCC high-risk group (8).…”