In addition to specific antiviral regimens, the
guidelines also include recommendations on monitoring during treatment,
managing side-effects and drug-drug interactions, improving adherence and
options for re-treatment of non-responders.
Re-treatment is largely dependent
on what regimen a person received initially and whether they carry
drug-resistant viral variants. For people starting treatment for the first
time, Pawlotsky suggested it may be advantageous to "slightly over-treat"
with first-line therapy – rather than trying to shorten treatment or reduce
the number of drugs as much as possible – to avoid the need for re-treatment.
While monitoring HCV viral load before, during and
after treatment was a critical aspect of treatment with interferon-based
therapy, "monitoring HCV RNA on therapy will
not help you make decisions about treatment [with DAAs]," Pawlotsky
stressed. "If it goes down fast, that's good,
but it doesn’t predict a cure."
HIV and HCV co-infection, studies have shown that people with co-infection and people
with HCV mono-infection respond equally well to interferon-free therapy, and
indications for treatment are therefore now "identical" save for
taking into account drug-drug interactions with antiretroviral therapy, said
panel member Puoti. With some 30 antiretrovirals available, "now it is possible to treat all patients with HIV [for hepatitis C]
without changing their antiretroviral regimen," though in some cases dose
adjustments may be indicated. "HIV specialists are used to managing
drug-drug interactions," he added.
Looking at people who are awaiting or have received a
liver transplant, treatment recommendations are not as definitive, with several
areas of remaining uncertainty. Treatment is generally indicated pre-transplant
as it can prevent infection of the donor liver graft. But the optimal timing
requires individual assessment, Pawlotsky said.
In some cases, it may be best to give very sick
patients a transplant right away, if available, and then start treatment once
they have their new functional liver. While curing hepatitis C remains the
primary goal, effective treatment could have the unfortunate effect of reducing
a patient's CPT and MELD scores enough to lower their priority for
transplantation, but not enough so that they no longer need one – a situation
Jensen dubbed "MELD purgatory."
The guidelines also contain sections on treating other
special populations including people with HBV co-infection, people with
chronic kidney disease and those undergoing kidney dialysis (the safety of
sofosbuvir may be reduced in these patients), people with bleeding disorders,
and active substance users and people on opioid substitution therapy.
"HCV treatment must be considered for [people who
inject drugs], provided they wish to receive treatment and are able and willing
to maintain regular appointments," the guidelines state. "HCV
treatment has been delivered successfully to drug users through various
clinical models, including within general hospital liver disease and viral
hepatitis clinics, drug detoxification clinics, opioid substitution therapy
clinics, prisons, and community-based clinics." While DAA trials have
usually excluded people who are currently using drugs, many have included participants on opioid
substitution therapy, and drug-drug interaction studies to date have not found
clinically important interactions with methadone