final program.qxd - Parallels Plesk Panel

OP 9.3
Future options in non responders and relaspers after current anti HCV therapy
Marc Bourlière, MD 1
1
Service Hépato-gastroentérologie, Hôpital Saint Joseph, Marseille, France
Pegylated interferons in combination with ribavirin, allow viral eradication in 54-66% of
treatment-naïve patients (1-5). Although the response rates seen with pegylated
interferons plus ribavirin are substantially greater than with earlier therapeutic
interventions such as conventional interferon mono- and combination therapy, a
proportion of those treated still fail to achieve a sustained virological response (SVR).
Thus, non-responders to prior antiviral therapy comprise a growing, and increasingly
important population of hepatitis C patients.
Natural history studies indicate that between 3-20% of individuals who remain infected
with hepatitis C virus (HCV) will develop cirrhosis over a period of 20-25 years, and these
patients are also at risk of developing end-stage liver disease and hepatocellular
carcinoma. Eradication of HCV following successful therapeutic intervention has
numerous benefits, including a reduced risk of progressive liver disease, regression of
fibrosis, improved quality of life, and a reduced risk of HCV transmission to others.
A lack of response to anti-HCV treatment can generally be categorised as either a
complete non-response (where HCV RNA levels do not significantly decline by >2-log10
throughout therapy), or virological relapse (where HCV RNA becomes undetectable
during treatment but is detected again after discontinuation of therapy).
Retreatment studies have generally shown a differing pattern of response among
non-responders and relapsers, with relapsers showing a greater SVR rate than true
non-responders.
Non-response to treatment can be attributed to a number of potential factors, which fall
into two broad categories.
i) Therapeutic insufficiency. In this situation the dose of interferon and/or ribavirin, or the
duration of treatment, have been inadequate and have failed to maintain sufficient
antiviral pressure to eradicate HCV(6,7).
ii) Virological resistance. Despite sufficient doses of interferon and ribavirin and an
adequate duration of therapy, the patient remains HCV RNA-positive. Numerous host-,
viral-, and disease-related factors have been shown to compromise the efficacy of
anti-viral therapy (8).
1) Retreatment of Patients Whose Non-Response is Attributed to Therapeutic
Insufficiency
There are a number of different factors which can contribute to the overall success, or
failure, of initial anti-HCV treatment. While the majority of host-, viral- and disease-related
factors associated with a reduced response rate cannot be modified, factors that
contribute to 'therapeutic insufficiency' during initial treatment (such as the type of
previous treatment, adherence and side effects) can be improved, and this should be
considered prior to starting retreatment.
Due to the increased SVR rate associated with pegylated interferons in treatment-naive
patients, those who have failed to eradicate HCV with an initial course of conventional
interferon mono- or combination therapy may benefit from retreatment with the newer,
more effective pegylated interferon/ribavirin combination regimen (9-12).
“ Focusing FIRST on PEOPLE “ 72 w w w . i s h e i d . c o m