A regimen of sofosbuvir/ledipasvir (Harvoni) taken for six weeks cured all
patients with genotype 1 acute hepatitis C virus (HCV) infection, including
those with high viral loads, according to findings from a German study presented
on Saturday at the 2016 International Liver
Congress in Barcelona. The researchers said treating hepatitis C early with a
short regimen would improve symptoms sooner, prevent HCV transmission and cost
less than treatment initiated during chronic infection.
Studies done in the interferon era
showed that treating people in the acute phase of HCV infection led to higher
response rates and required a shorter duration than treatment of chronic
infection. But because interferon-based therapy is poorly tolerated, many
preferred to wait to see if the immune system would naturally clear HCV, which
happens approximately 25% of the time.
The advent of interferon-free
direct-acting antiviral (DAA) therapy has made chronic hepatitis C treatment
shorter, better tolerated and more effective, leading experts to expect the
same may be true for acute HCV infection. Yet there are currently no DAA
regimens approved specifically for the treatment of acute hepatitis C, with current guidelines recommending
the same options as used for chronic infection.
- direct-acting antiviral (DAA)
A drug which prevents hepatitis C from reproducing by blocking certain steps in its lifecycle.
Katja Deterding and Heiner Wedemeyer of Hannover
Medical School and fellow investigators with the German HepNet Acute HCV IV
Study evaluated the safety and efficacy of sofosbuvir/ledipasvir for people
with acute hepatitis C mono-infection. Dr Deterding presented the findings at a
late-breaker session and Prof. Wedemeyer gave an overview during a press
This is the latest in a series of HepNet investigator-initiated acute
hepatitis C studies. The others looked at interferon regimens taken for six
months and saw sustained response rates ranging from 90 to 98%.
The prospective pilot study enrolled 20 participants
at 10 centres in Germany between November 2014 and October 2015. Most (60%)
were men and the mean age was 46 years. People with HIV co-infection were not
Acute HCV infection was defined as having known or
suspected exposure to HCV within the prior four months, documented
seroconversion from HCV antibody negative to positive, or an alanine
aminotransferase (ALT) liver enzyme level more than 10 times the upper limit of
normal – an indicator of acute liver inflammation.
The most commonly reported risk factors for HCV
infection were sexual transmission (11 people or 55%) and medical procedures or
needlestick injuries (five patients or 25%); only one reported injection drug
use. Five of the suspected sexual transmissions were among men who have sex
with men, with the remainder among heterosexual men and women. Although
outbreaks of sexually transmitted HCV have been seen among HIV-positive gay
men, heterosexual transmission is thought to be rare and HIV-negative gay men
have HCV infection rates similar to those of the general population.
Eleven people had harder-to-treat HCV genotype 1a,
while nine had 1b. Pre-treatment HCV viral load ranged from 3.3 to 6.7 log10
IU/ml. The mean ALT level was 463 IU/l and the mean bilirubin level was 24
mg/dl. But some patients had
very high levels, Prof. Wedemeyer said; the highest ALT level was over 2700
IU/ml and some patients had such high bilirubin levels they had icterus or
jaundice, with yellowing of the skin and eyes.
All study participants were treated with sofosbuvir/ledipasvir
in a fixed-dose co-formulation (400/90mg), without ribavirin, for six weeks. The usual recommended
duration of sofosbuvir/ledipasvir for chronic hepatitis C treatment is 12
weeks, though people with no prior treatment experience, no cirrhosis and low
viral load can be treated for eight weeks.
Everyone completed the full course of treatment and
all had sustained virological response, or continued undetectable HCV RNA at
the end of a 12-week post-treatment follow-up period (SVR12).
looked at the relationship between baseline viral load and early virological
response. People with higher viral loads suppressed HCV more slowly, but all
were undetectable by the end of treatment. This raises the prospect that an even
shorter treatment duration may be adequate for some people.
Along with viral suppression, the patients experienced
rapid biochemical response, or sharp declines in liver enzymes and bilirubin,
with ALT normalisation and normal bilirubin levels by the end of treatment.
Treatment was generally safe and well-tolerated. There
was one unrelated serious adverse event and no-one discontinued treatment early
due to side-effects. The most frequently reported adverse events were
gastrointestinal symptoms (20%), fatigue (15%) and hair loss (15%).
"Short treatment of only six weeks was highly
effective with an SVR12 rate of 100% in acute HCV genotype 1 mono-infected
patients," the researchers concluded. "High baseline viral load was
associated with a delayed virological response, which however did not lead to
After Dr Deterding’s presentation, Prof. Jürgen Rockstroh of the
University of Bonn pointed out that his group conducted a study of the same
regimen for HIV-positive men with acute HCV co-infection. As he
reported at the recent Conference on Retroviruses and Opportunistic Infections, six weeks
of therapy cured co-infected people with low HCV viral load, but there were three relapses
among patients with high baseline HCV RNA levels. These, along with a case of
reinfection and two people lost to follow-up, resulted in an SVR12 rate of just
told aidsmap.com that unlike in Prof. Rockstroh’s study, the HIV-negative patients
with high viral load in the HepNet study "cleared more slowly but stayed
cleared." While some experts are now saying people with HIV and HCV co-infection
are no longer a ‘special population’ when it comes to hepatitis C, he suggested
"there is still a difference", even if they have high CD4 counts and
At both the
press briefing and the late-breaker session, attendees brought up the issue of
delaying treatment for acute HCV infection to see if spontaneous clearance will
occur, as was common practice in the interferon era.
recommend to start [during acute infection] due to the high SVR rate and rapid
improvement of symptoms," Dr Deterding responded.
If treatment is
delayed, "patients would be ill for months," which could interfere
with employment and lead to stigma due to jaundice, Prof. Wedemeyer elaborated.
It usually takes up to eight weeks for liver enzymes and bilirubin to normalise
after acute infection, compared to just one week in this study.
added that early treatment is also important for preventing HCV transmission,
given that viral load is often high during the acute stage. Further, he noted,
cutting treatment duration from 12 weeks during chronic infection to six weeks
during acute infection would reduce the price by half, which "could be an enormous
health cost savings."