Tania Welzel of
Goethe University in Frankfurt,
Germany, presented findings from a multicentre compassionate use programme
in the European Union (AI444-237).
included 102 people with genotype 3 chronic hepatitis C, considered at high
risk of hepatic decompensation or death within 12 months if they did not
receive treatment. All were included in the safety analysis and 82 were
included in the efficacy analysis (20 did not reach the 12-week post-treatment
analysis or had missing data).
Nearly 70% were
men, 88% were white and the median age was 55 years; 15% had HIV co-infection and
5% also had hepatitis B. Over half (59%) had received prior hepatitis C
treatment. Most (85%) had liver cirrhosis, of whom 47% had Child-Pugh (CP)
class A, 39% had class B and 13% had class C. The median MELD score – a measure
of liver function impairment – was 10, and 10% had a score greater than 15. The
group included eight liver transplant recipients.
were treated with 60mg daclatasvir and 400mg sofosbuvir. Physicians had the
option to add ribavirin, and this was done in 39% of cases. Most people were
treated for 24 weeks but providers could opt for a shorter duration.
At 12 weeks
post-treatment, 86% of people treated with daclatasvir and sofosbuvir alone,
and 88% who added ribavirin achieved SVR12 in an intention-to-treat analysis.
There was one viral breakthrough during treatment, six relapses, one
discontinuation due to an adverse event and three deaths.
were 91% without and 100% with ribavirin for treatment-naive patients, and 82%
and 81%, respectively, for those treated previously. SVR12 rates were 86%
without and 71% with ribavirin for the small number of people treated for only
12 weeks. Response rates for people with HIV and HCV co-infection were 83%
without and 100% with ribavirin, and all transplant recipients were cured
either with or without ribavirin, but these numbers were small.
were about the same for people with cirrhosis treated with or without ribavirin
– 86% vs 88%, respectively – but there were some differences according to liver
disease severity. Among those using daclatasvir and sofosbuvir alone, SVR12
rates were 100% for CP class A, 80% for class B and 75% for class C.
Conversely, among those who added ribavirin, response rates were 85%, 86% and
100%, respectively. A similar pattern was seen according to MELD scores.
generally improved with treatment, with ALT and total bilirubin levels falling
on average, while albumin levels and platelet counts rose.
A majority of participants
in the study experienced adverse events – as expected for such a sick
population – but treatment-related serious adverse events were uncommon (3%
without and 5% with ribavirin). There were six adverse events leading to
treatment discontinuation or death. No one experienced severe ALT or AST liver
enzyme or creatinine elevations. Three people in the daclatasvir plus
sofosbuvir arm and four who added ribavirin developed anaemia.
"In a real-life clinical setting, [daclatasvir +
sofosbuvir with or without ribavirin] achieved high SVR rates (87%) in HCV
genotype 3-infected patients at high risk of hepatic decompensation or
death," the researchers concluded. "These findings suggest that
[daclatasvir + sofosbuvir with or without ribavirin] is an effective and
well-tolerated oral treatment for patients with genotype 3 infection, including
those with most advanced disease."