People with HIV/HCV co-infection can use the
same regimens as HIV-negative people – and cure rates are the same for both
groups – but they need to take into account the potential for drug-drug
interactions with antiretroviral therapy. Sofosbuvir-based regimens and
daclatasvir have fewer interactions than other HCV regimens, though
sofosbuvir/velpatasvir should not be taken with most NNRTIs including the
widely used efavirenz (Sustiva).
"In
HIV patients HCV screening is almost universal, and it is possible to eradicate
HCV in this population that has a high rate of liver-related death," said
Massimo Puoti.
People with HCV/hepatitis B virus (HBV) co-infection can be treated for hepatitis C according
to the general recommendations, but they should be carefully monitored because
HBV may become more active once HCV is eliminated, and they may need to start
HBV antivirals such as tenofovir (Viread)
or entecavir (Baraclude).
People with decompensated cirrhosis remain one of the
most challenging groups to treat. Those who are not on a waiting list for a
liver transplant should be treated urgently, according to the guidelines.
However, those with current or past decompensation (Child-Pugh class B and C)
should not use HCV protease inhibitors (grazoprevir, paritaprevir or
simeprevir), as they can lead to worsening liver failure and death. The
recommended regimens for these people are sofosbuvir/ledipasvir,
sofosbuvir/velpatasvir or sofosbuvir plus daclatasvir, all with ribavirin if
tolerated.
People with
decompensated cirrhosis but without hepatocellular carcinoma (HCC) who are awaiting a liver transplant should
be treated for hepatitis C if they have a MELD score below 18-20. In some cases
they may improve enough that they no longer need a transplant. Those with
higher MELD scores should receive a transplant first and be treated afterwards,
unless their expected waiting time is more than six months. People on the
transplant list with HCC should be treated before transplantation if possible.
If HCV recurs after a liver transplant, treatment
should be started as soon as possible once the patient is stabilised after
surgery. Recommended regimens are sofosbuvir/ledipasvir or sofosbuvir plus
daclatasvir, both with ribavirin. Sofosbuvir/velpatasvir may become an option
once its interactions with immune-suppressing drugs are known.
People with chronic kidney disease who
have an estimated glomerular filtration rate (eGFR) >30 ml/min can be
treated according to the general recommendations. Those with worse kidney
disease or receiving kidney dialysis should use sofosbuvir with caution.
People with genotypes 1 or 4 can use the paritaprevir-based 3D regimen or
grazoprevir/elbasvir; those with other genotypes can use sofosbuvir-based
regimens with close monitoring of kidney function.
People who were not cured with prior
DAA treatment are generally easy to treat using the recommended regimens if
they were not previously exposed to NS5A inhibitors (daclatasvir, ledipasvir or
velpatasvir). Those who were exposed can try regimens containing sofosbuvir
plus two or three other DAAs and ribavirin – for example sofosbuvir plus the 3D
regimen or grazoprevir/elbasvir – but these off-label combinations are expensive and have very
limited safety data.
"The
experience of the panel is that only these kinds of combinations can work, and
even these combinations do not always work when you retreat patients who have
selected NS5A-resistant viruses," Prof Pawlotsky cautioned. "This is
another reason to optimise therapy from the very beginning."
For
people who inject drugs – both active injectors and people on opioid
substitution therapy – decisions about treatment should be made on a
case-by-case basis. "HCV treatment must be considered for [people who
inject drugs] who are willing to receive treatment, are able and willing to
maintain regular appointments and adherence, and accept to undergo integrated
management of their substance abuse, including syringe exchange program,
substitution therapy and other general harm reduction strategies," the
guidelines advise.
The C-EDGE CO-STAR trial found that people on opioid substitution
therapy treated with grazoprevir/elbasvir had response rates, adherence and
side-effects similar to those of non-drug users in other studies. Modelling
studies suggest that hepatitis C treatment for people who inject drugs could
reduce transmission when combined with other prevention measures.
For people with acute HCV infection, the panel recommended
sofosbuvir/ledipasvir, sofosbuvir/velpatasvir or sofosbuvir plus daclatasvir
without ribavirin, generally for 8 weeks, but extended to 12 weeks for
HIV-positive people or those with high HCV viral load.