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
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.
- alanine transaminase (ALT)
is an enzyme found in the liver that helps the body metabolise protein. When
the liver is damaged, ALT is released into the bloodstream, resulting in elevated enzymes in blood tests.
enzyme that can be measured in a blood sample that indicates the health of the
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
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
"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
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.
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).
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.
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