Two combinations proved highly effective in curing hepatitis
C in people who had experienced the failure of a previous combination containing
an NS5A inhibitor, studies in Europe and New Zealand show.
The findings, presented at the International Liver Congress
this week, provide reassurance that the vast majority of people with hepatitis
C who experience the failure of their first treatment combination can be cured
with a follow-up course of treatment, without the need for adding the potentially
toxic drug ribavirin.
Re-treatment after failure of a direct-acting antiviral
combination that contains an NS5A inhibitor (daclatasvir, ledipasvir, elbasvir,
pibrentasvir or velpatasvir) may be challenging if resistance to the NS5A
inhibitor emerges as a result of treatment failure.
- decompensated cirrhosis
The later stage of
cirrhosis, during which the liver cannot perform some vital functions and
complications occur. See also ‘cirrhosis’ and ‘compensated cirrhosis’.
European and US guidelines recommend 12 weeks of treatment with
voxilaprevir/velpatasvir/sofosbuvir (Vosevi) or 12 weeks of glecaprevir/pibrentasvir
(Maviret) plus sofosbuvir (Sovaldi), with or without ribavirin.
However, each recommendation is based on small numbers of treated patients and
the added value of using ribavirin as an extra drug in these cases of treatment
failure is uncertain.
An international study looked at real-world responses to the
three-drug combination voxilaprevir/velpatasvir/sofosbuvir (Vosevi) in
people who had experienced the failure of at least one previous regimen. The
study recruited all patients re-treated with this combination at 153 liver clinics
in Austria, Belgium, Germany and Switzerland between May 2015 and November
The study recruited 458 participants with a median age of 55
years, 79% male, predominantly genotype 1 (54%) or genotype 3 (39%). Participants
received Vosevi for 12 weeks; 4% received ribavirin too.
Of those recruited, 427 were evaluable. Of these, 26
relapsed after the completion of treatment, a cure rate of 94%.
Treatment failure occurred more frequently in people with
genotype 3 infection and those with hepatocellular carcinoma but the
effectiveness of treatment was not affected by baseline hepatitis C RNA level,
previous DAA regimen or the presence of cirrhosis. The presence of resistance
mutations did not compromise the effectiveness of treatment.
Another study, carried out in New Zealand, looked at responses
to re-treatment with glecaprevir and pibrentasvir (Maviret) and generic
sofosbuvir for 16 weeks in people whose first regimen had failed and who had NS5A
resistance mutations. The study excluded people with decompensated cirrhosis or
hepatocellular carcinoma, as well as people with post-transplant hepatitis C.
Vosevi is not available and Sovaldi is not
approved for re-treatment of hepatitis C in New Zealand, so the study investigators
added generic sofosbuvir, supplied by Pharco in Egypt, to glecaprevir/pibrentasvir.
The study recruited 66 participants, 54% with previous
failure of a glecaprevir/pibrentasvir regimen, 38% with failure of ombitasvir,
paritaprevir, dasabuvir and ritonavir, and the remainder with failure of grazoprevir/elbasvir, ledipasvir/sofosbuvir or sofosbuvir/velpatasvir.
Six patients had experienced failure of more than one regimen. Thirty-nine
per cent had multiple NS5A resistance mutations.
completed treatment and had post-treatment HCV RNA results available. Fifty of
51 had been cured (98%).
participants were lost to follow-up and three interrupted treatment during the
study. Dr Gane said that the biggest challenge to curing people who had
experienced first-line failure was social factors and non-adherence, not drug
resistance. “The most common reason for DAA treatment failure now is
non-virologic,” he concluded. Rather than worrying about drug resistance, or whether
to add ribavirin, adherence and loss to follow-up were the problems that need
to be addressed.
He said the study
findings emphasised the need for wrap-around support for people undergoing
hepatitis C treatment, including psychosocial interventions, daily dispensing
for people who are using drugs or receiving opioid substitution therapy and
outreach teams who can deliver medication and follow-up people in the