Six weeks of sofosbuvir/ledipasvir cures genotype 1 acute hepatitis C in people without HIV

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 earlier this month in Boston.

Studies done in the interferon era showed that treating people during the acute phase of HCV infection – within the first six 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 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 of Hannover Medical School in Germany and colleagues with 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; people with HIV/HCV co-infection were not included.

This pilot study enrolled 20 participants at 10 centres 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 people had very high ALT levels and jaundice. The most common risk factors for HCV infection were sexual transmission (11 people, including five men who have sex with men) and medical procedures or needle-stick injuries (five people).

All study participants were treated with sofosbuvir/ledipasvir in a fixed-dose co-formulation (400/90mg) without ribavirin for 6 weeks. The usual recommended duration of sofosbuvir/ledipasvir for chronic hepatitis C treatment is 12 weeks, although people 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). Dr 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 study participants completed treatment and all achieved SVR12. However, one 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 summarised. "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 individuals with HIV/HCV co-infection, 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 (CROI 2016), Jürgen Rockstroh of 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 people with HIV/HCV co-infection with low baseline HCV viral load, but there were three relapses among people with high HCV RNA levels; these relapses, along with a case of reinfection and two 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.