Successful adherence to hepatitis C treatment may require
physicians and care teams to address a wide range of factors, according to
research from the United States
and Germany presented at The Liver Meeting 2012, the
63rd annual meeting of the American Association for the Study of Liver
Diseases (AASLD) in Boston last month.
Hepatitis C treatment presents a number of adherence
challenges that are distinct from other disease areas, due to the use of
pegylated interferon, which causes both physical and psychological side-effects
that affect numerous areas of a patient’s life during a treatment course that
may last up to 48 weeks, and which may be undergone several times if the first
course is unsuccessful.
Non-adherence to pegylated interferon and ribavirin often
consists of non-completion of the treatment course, but a large cohort study of US
veterans has also observed that adherence to ribavirin (as measured by
prescription refills) declined after the first 12 weeks of therapy, even if
the treatment course was completed, and that sustained virologic response was
associated with higher levels of ribavirin adherence throughout the 48-week
An inherited gene which all individuals have. There are three genotypes of IL28B; these influence response to hepatitis C and its treatment. People with CC genotype are more likely to spontaneously clear acute infection or (during chronic infection) respond well to interferon-based treatment. The other two genotypes are known as CT and TT.
New direct-acting antivirals (DAAs) also present adherence
challenges, because they must be taken up to three times a day for 12 to 24 weeks
in most cases, and can cause side-effects that also interfere with daily
In addition to non-completion of the treatment course,
missing doses of antivirals is a problematic form of non-adherence to
DAA treatment, because it presents a risk of loss of virological control, resulting
either in failure to achieve a rapid virologic response during the first four
weeks of treatment (RVR), or in viral breakthrough after initial suppression
has been achieved. This may lead to drug resistance to the antiviral agent.
people’s ability to adhere to treatment requires an understanding of
behavioural as well as biological factors, including socioeconomic status,
access to treatment, the disease stage, a patient’s individual ability to adapt
and moderate behaviour, the treatment itself, its side-effects and cost.
Lauren Rover of George
Virginia, and Inova Health Systems, a large
non-profit healthcare provider in northern Virginia, told a conference session that, for
short-term treatment regimens, adherence rates of 70 to 80% are often achieved.
For longer-term treatments, adherence rates drop to 40 to 50%, while adherence
rates for therapies that also include an element of behaviour change are stuck
at around 20 to 30%.
It is worth noting, however, that in one disease area – HIV
infection – long-term adherence rates are closer to those for short-term
medication courses than for chronic medication, due in part to the
simplification of therapy and the provision of intensive adherence support.
Rover and colleagues carried out a study to examine the
correlation between a range of psycho-behavioural measures and adherence to
pegylated interferon and ribavirin in 63 people. Sociodemographic information included sex, race,
substance use history, state of marriage and employment. Economic status and
education were not measured.
scores were based on:
showing up to appointments
“adherence to doctor’s
filling out forms correctly.
patient-reported outcomes were assessed at baseline: expressing anger verbally
or physically, level of angry reactions, anger as part of personality (“trait
anger”), and expression of anger, all of which were higher in those who were
already taking antidepressants at baseline; higher levels of emotions and
worry were expressed by the same group all the way through the study. Of those
patients (84%) who completed all patient reports, 45 individuals (71%) adhered
to treatment (as defined) and 18 (29%) did not. Adherence was significantly
lower in those who reported more frequently that they felt like expressing
anger verbally (p < 0.01), and patients who reported more anger and worry at
baseline were less likely to adhere to the course of treatment.
research group concluded that it may be helpful to assess levels of anger and
worry before treatment, and to use psycho-behavioural measures as a tool for
monitoring people during treatment and to address need for specific
issue not reported on was how many people started antidepressants during the
study (a not-uncommon occurrence with pegylated interferon) and if that changed
outcomes within that group.
the two groups measured (those who were adherent to treatment and those who were not), age (47 vs
46 years old), marriage, substance-use history and employment were all similar,
and therefore not considered predictive factors in adherence. Men had better
adherence scores, as did Caucasians.
discussions after the presentation, the session moderator and audience members
suggested that lower adherence in women may be explained by women putting their
roles as caregivers above their own health needs, and by possible gender
differences in adverse events that affect treatment adherence. Both areas
require further research.
lower adherence in non-Caucasians may be a consequence of poorer early
virological outcomes due to an unfavourable IL28B (non-CC) genotype, rather
than a determinant of virologic response, since poor early response may act as
a disincentive to subsequent adherence. Once again, further research would be