A short course of sofosbuvir/ledipasvir (Harvoni) taken for 6 weeks cured 100% of HIV-negative people with genotype 1 acute hepatitis C virus (HCV) infection, including those with high viral loads, according to study results presented at the 2016 AASLD Liver Meeting in Boston.
Studies done in the interferon era showed that treating people during the acute phase of HCV infection — within the first 6 months — led to higher response rates and required a shorter duration of therapy than treatment of chronic infection. The advent of interferon-free direct-acting antiviral (DAA) therapy has made treatment of chronic hepatitis C treatment shorter, better tolerated, and more effective, leading experts to ask if this would also be the case for acute HCV infection.
Around a quarter of people will naturally clear HCV, and given that interferon-based therapy was poorly tolerated, many patients and providers preferred to wait and see if this would occur before starting treatment. Direct-acting antiviral therapy is well-tolerated, but its high cost may be another reason to wait. On the other hand, prompt treatment during acute infection can improve symptoms sooner and prevent onward HCV transmission at a time when viral load may be high.
Katja Deterding from Hannover Medical School in Germany and colleagueswith the German HepNet Acute HCV IV Study assessed the safety and efficacy of sofosbuvir/ledipasvir taken for 6 weeks for people with acute hepatitis C monoinfection; HIV/HCV coinfected people were not included.
This pilot study enrolled 20 participants at 10 centers in Germany. A majority (60%) were men and the mean age was 46 years. Over half (55%) had harder-to-treat HCV genotype 1a, the rest had 1b. The mean alanine transaminase (ALT) level was 463 IU/L and the mean bilirubin level was 24 mg/dL, but some patients had very high ALTlevels and jaundice. The most common risk factors for HCV infection were sexual transmission (11 people, including 5 men who have sex with men) and medical procedures or needle-stick injuries (5 people).
All study participants were treated with sofosbuvir/ledipasvir in a fixed-dose coformulation (400/90 mg) without ribavirin for 6 weeks. The usual recommended duration of sofosbuvir/ledipasvir for chronic hepatitis C treatment is 12 weeks, although patients with no prior treatment experience, no cirrhosis, and low HCV viral load can be treated for 8 weeks.
The primary study endpoint was sustained virological response at 12 weeks after completion of treatment (SVR12). Deterding presented these results at this year’s EASL International Liver Congress. The poster at the Liver Meeting looked at continued follow-up through 24 weeks post-treatment.
- All 20 treated participants achieved SVR12.
- 1 person was later lost to follow-up, so the SVR24 rate fell to 95%.
- People with high baseline HCV RNA took longer to reach viral suppression, but all had undetectable viral load by the end of treatment.
- Study participants experienced steep declines in ALT and bilirubin, reaching normal levels by the end of treatment.
- Treatment was generally safe and well-tolerated with no drug-related serious adverse events.
“Short treatment of only 6 weeks was highly effective with an SVR12 rate of 100% in acute genotype 1 monoinfected patients,” the researchers summarized. “High baseline viral load was associated with a delayed virological response — which however did not lead to treatment failures. A rapid biochemical response was observed in patients with severe acute hepatitis C treated with an interferon-free regimen.”
Given that more than half of study participants achieved undetectable viral load by week 4 of treatment, they suggested that even shorter durations remain to be studied.
The efficacy of 6 weeks of sofosbuvir/ledipasvir needs to be confirmed for other HCV genotypes, they added. People with genotype 3 would likely do better with a pangenotypic regimen such as sofosbuvir/velpatasvir (Epclusa).
The effectiveness of this regimen also needs to be confirmed for HIV/HCV coinfected individuals, as HIV-positive people are more likely to acquire HCV via sexual transmission, are more frequently monitored for liver abnormalities, and make up a substantial proportion of people diagnosed during acute HCV infection.
At this year’s Conference on Retroviruses and Opportunistic Infections, Jürgen Rockstroh from the University of Bonn reported findings from a study of the same sofosbuvir/ledipasvir regimen for HIV-positive men with acute HCV. In that study 6 weeks of therapy cured HIV/HCV coinfected people with low baseline HCV viral load, but there were 3 relapses among patients with high HCV RNA levels; these relapses, along with a case of reinfection and 2 people lost to follow-up, resulted in an SVR12 rate of just 77%.
The HepNet researchers encouraged treatment of acute HCV infection rather than waiting for possible spontaneous clearance, as treating early with a short regimen rapidly improves acute hepatitis C symptoms, could prevent transmission of HCV in high-risk populations, and could be cost-saving compared with longer treatment of chronic hepatitis C.
By Liz Highleyman
K Deterding, CD Spinner, E Schott, H Wedemeyer, et al. Six weeks of sofosbuvir/ledipasvir treatment of acute hepatitis C virus genotype 1 monoinfection: Final results of the The German HepNet Acute HCV IV Study. AASLD Liver Meeting. Boston, November 11-15, 2016. Abstract 847.