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."
Regarding HIV/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 or buprenorphine.
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