Hepatitis C treatment managed by non-specialists
such as primary care physicians and nurse practitioners is as safe and
effective as treatment delivered by specialists and could help increase the
number of people receiving therapy, according to findings from the ASCEND study
presented at the 2016 International Liver
Congress this week in Barcelona.
The advent of direct-acting
antivirals (DAAs) used in interferon-free regimens has made chronic hepatitis C
treatment simpler, shorter, more tolerable and much more effective. While interferon-based
therapy required expertise to determine who needs treatment for progressive
liver disease and when to discontinue futile therapy, treatment with DAAs is
more straightforward and can potentially be managed by a wider variety of
The latest EASL guidelines and AASLD/IDSA
guidelines recommend that everyone with chronic
hepatitis C should be considered for treatment rather than waiting until they
develop advanced liver disease, making eradication of hepatitis C virus
(HCV) an achievable goal. But challenges remain,
including the high cost of therapy and the lack of enough specialists to treat
everyone living with the disease.
Sarah Kattakuzhy of the University of Maryland
and colleagues conducted the ASCEND trial to evaluate the safety and effectiveness of task
shifting of hepatitis C treatment to community-based non-specialist providers.
"Currently, the limited availability of experienced specialists
restricts rapid expansion of hepatitis C treatment, compromising the goal of
global eradication," Kattakuzhy said. "As such,
care models which bypass this therapeutic bottleneck must be explored."
This open-label, phase 4 trial enrolled 600 people
with chronic hepatitis C at two urban community health centres in Washington,
DC, who started treatment between May and November 2015.
About 70% were men, almost all (96%) were black
and the average age was approximately 59 years. Nearly a quarter had HIV
co-infection. A majority (72%) had hard-to-treat HCV genotype 1a (the rest had
1b), 18% were hepatitis C treatment-experienced and 20% had compensated liver
cirrhosis. Patient characteristics were comparable across provider assignments.
A total of 16 providers participated in the study: six hepatologist or
infectious disease specialists, five primary care physicians and five nurse
practitioners. Patients were allocated in a non-randomised manner to receive
treatment from the specialists (n = 294), primary care doctors (n = 156) or
nurses (n = 150). All providers underwent the same three-hour training on the
All patients were treated with sofosbuvir/ledipasvir (the drugs in Harvoni) according to US Food and Drug
Administration (FDA) label directions. Most patients (90%) were treated for 12
weeks; although more than 300 met the label criteria for 8 weeks of therapy, only
29 received this shorter duration.
Overall, 71 patients discontinued treatment early, mostly
due to loss to follow-up (53 people). Seven stopped due to adverse
events, five due to personal decision and three due to death unrelated to study
participation. Kattakuzhy noted that the 9% loss to follow-up
was consistent with other studies of real-world urban populations.
The primary outcome was sustained virological response, or undetectable
HCV RNA at 12 weeks after completion of treatment (SVR12).
The overall SVR12 rate was 94.2% in a per-protocol analysis of 382
patients with available data. Cure rates were statistically similar
for patients treated by primary care physicians (97.3%), nurse practitioners (95.2%) and
HIV co-infection status had no impact on SVR12 rates overall (90.9%) or
by provider type (90.9, 88.9 and 91.2%, respectively). The only factor
significantly associated with treatment failure was having genotype 1a as
opposed to 1b.
Overall, adherence to treatment dropped off over time in all provider
groups. Among the 456 patients who completed 12 weeks of therapy, however, cumulative
adherence was significantly lower among people treated by specialists (63.8%) compared
to those treated by nurse practitioners (81.5%) or primary care physicians
"The ASCEND investigation
demonstrates that HCV treatment administered independently by primary-care
physicians and nurse practitioners is safe and equally effective as care
observed with experienced specialists, inclusive of challenging sub-populations
of the epidemic, and within the largest black cohort described to date," the
researchers concluded. "The ASCEND model could increase
the availability of community-based, non-specialist providers to significantly
expand the scale of HCV therapy, and bridge existing gaps in the hepatitis C
Kattakuzhy added that this may be especially
relevant for underserved and rural hepatitis C patients.
"We know we have too few experienced specialists treating HCV and
this is severely hampering our ability to eradicate this disease once and for
all," vice secretary of the European Association for the Study of the Liver
(EASL) Prof. Tom Hemming Karlsen stated in an EASL
press release about the study. "This research has the
potential to be a genuine game changer in the way we look at HCV treatment
across the board, and could provide the opportunity to increase access to care
and treatment to many regions of the world."