Sofosbuvir plus velpatasvir for 8 weeks in patients with acute hepatitis C: The HepNet acute HCV-V study

Abstract

Background & aims: EASL guidelines recommend 8 weeks of treatment with sofosbuvir plus velpatasvir (SOF/VEL) for the treatment of acute or recently acquired HCV infection, but only 6- and 12-week data are available. Therefore, the aim of this study was to evaluate the safety and efficacy of a shortened 8-week SOF/VEL treatment for acute HCV monoinfection.

Methods: In this investigator-initiated, prospective, multicentre, single-arm study, we recruited 20 adult patients with acute HCV monoinfection from nine centers in Germany. Patients received SOF/VEL (400/100 mg) as a fixed-dose combination tablet once daily for 8 weeks. The primary efficacy endpoint was the proportion of patients with sustained virological response 12 weeks after the end of treatment (SVR12).

Results: The median HCV RNA viral load at baseline was 104,307 IU/ml; the distribution of HCV genotypes was as follows: GT1a/1b/2/3/4: n = 12/1/1/3/3. Thirteen (65%) of the 20 patients were taking medication for HIV pre-exposure prophylaxis. SVR12 was achieved in all patients who complied with the study protocol (n = 18/18 [100%], per protocol analysis), but the primary endpoint was not met in the intention-to-treat analysis (n = 18/20 [90%]) because two patients were lost to follow-up. One serious adverse event (unrelated to study drug) occurred during 12 weeks of post-treatment follow-up.

Conclusions: The 8-week treatment with SOF/VEL was well tolerated and highly effective in all adherent patients with acute HCV monoinfection. Early treatment of hepatitis C might effectively prevent the spread of HCV in high-risk groups.

Clinical trial number: NCT03818308.

Impact and implications: The HepNet acute HCV-V study (NCT03818308), an investigator-initiated, single-arm, multicenter pilot study, demonstrates the efficacy and safety of 8 weeks of daily treatment with the fixed-dose combination sofosbuvir/velpatasvir (400/100 mg) in patients with acute hepatitis C virus (HCV) infection. All patients who completed therapy and were followed-up achieved sustained virologic response. Thus, early treatment with SOF/VEL which might effectively prevent the spread of HCV in high-risk groups can be recommended for patients with acute HCV monoinfection.

Keywords: ALT, alanine aminotransferase; HCV, hepatitis C virus; ITT, intention-to-treat; LLOQ, lower limit of quantification; PP, per protocol; SVR, sustained virologic response; ULN, upper limit of normal; acute HCV infection; direct-acting antivirals; hepatitis C elimination; recently acquired infection.

Graphical abstract

Fig. 1

Virological and biochemical response. (A) Response to antiviral treatment by patients with serum HCV RNA levels <10 IU/ml LLOQ in ITT and PP analysis. Two patients were lost to follow-up. Percentage of patients ±95 Wilson confidence interval. (B) Decline of ALT by scatter plot with median line; Friedman test with post hoc analysis (n = 20). ALT, alanine aminotransferase; ITT, intention-to-treat; PP, per protocol; SOF/VEL, sofosbuvir/velpatasvir; ULN, upper limit of normal.