Rates of hepatitis
C virus (HCV) reoccurrence after successful therapy differ markedly between
risk groups, according to the results of a meta-analysis presented at the
recent Conference on Retroviruses and Opportunistic Infections (CROI 2015) in Seattle, USA.
At one end of the
spectrum, over a fifth of people with HIV co-infection who cleared HCV
infection with treatment experienced a recurrence of the infection. This
compared to a rate of just 1% in people with no HCV risk factors. The UK
investigators leading the study believe these large differences point to
re-infection rather than relapse being the cause of the re-emergence of HCV
after treatment response.
HCV infection is
an increasingly important cause of liver-related illness and death around the
world. Diagnosing and treating HCV is therefore a global health priority,
especially as therapy with combinations of new direct-acting anti-HCV drugs can
achieve a cure or sustained virological response (SVR) – absence of HCV RNA 24
weeks after the completion of therapy – in up to 90% of patients.
- sustained virological response (SVR)
Undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 24 weeks (six months) after ending treatment and is considered to be a cure. SVR4 and SVR12 refer to RNA remaining undetectable for 4 and 12 weeks respectively.
But a minority of
people who have a successful response to therapy experience a subsequent
reoccurrence of HCV infection. Many treated patients continue to have an
ongoing risk of HCV infection, so it is possible that recurrences are due to HCV
re-infection rather than relapse after treatment.
To see if this is
the case, researchers looked at rates of HCV recurrence among patients who were
successfully treated for HCV.
The patients were
divided into three groups according to their HCV risk: low risk (mono-infected
patients with no risk factors for re-infection); high-risk (people who inject drugs and people in prison settings); and people with HIV/HCV co-infection.
treatment was defined as SVR 24 weeks after the completion of therapy. Recurrence was
defined as detection of HCV RNA six or more months after SVR.
Results of 66
separate studies involving over 11,000 people were analysed by the
investigators. Most individuals received treatment consisting of pegylated
interferon and ribavirin.
There were 43
studies involving low-risk patients (n = 9419). During a mean of 4.1 years of
follow-up, 87 of these individuals experienced a recurrence of HCV. This
provided a recurrence incidence of 0.23 per 100 person-years and a five-year
recurrence rate of just over 1%.
involved high-risk patients (n = 819). These individuals were followed for a
mean of 2.9 years post-SVR and during this time 53 individuals had a recurrence
of the infection. The incidence rate was 2.8 per 100 person-years, and there
was a 13% five-year recurrence rate.
There were seven
studies involving people with HIV and HCV co-infection (n = 833). There were 123
cases of HCV recurrence during a mean of 3.1 years of follow-up. Incidence was
4.78 per 100 person-years, and the five-year recurrence rate was almost 22%.
Five-year incidence among people with co-infection differed according to study
design, and was a little over 1% for those enrolled in randomised controlled
trials but 25% for those in cohort studies.
Because of the
large differences in outcomes between risk groups, the investigators conclude
that most HCV recurrences after SVR are probably due to re-infection due to
ongoing risk rather than relapse.