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Introduction:
Millions of people worldwide suffer from hepatitis
C, which can lead to severe liver disease, liver
cancer, and death. Numerous previous interventions
have been used for hepatitis C, but none of these
interventions have proven effective on patient-
centred outcomes. DAAs are relatively new but
expensive interventions for hepatitis C, and
preliminary results have shown that DAAs seem to
eradicate hepatitis C virus from the blood (sustained
virological response).However, it is questionable if
an eradication of hepatitis C virus in the blood leads
no hepatitis C in the body and improved survival
and fewer complications. In this Cochrane Review,
the authors assessed the evidence on the clinical
effects of DAAs for hepatitis C.
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VIRALLIFECYCLEANDREPLICATION:-
The main targets of the direct-acting antiviral
agents are the HCV-encodedproteins that are vital
to the replication of the virus (figure 1).The
infectious viral structure is comprised of envelope
glycoproteins in a lipid bilayer that contain the viral
core protein and RNA [2]. After cell entry, the viral
RNA is translatedthrough host machinery into a
polyprotein, which is cleaved during and after
translation by both host and viral-encoded proteases
into 10 mature viral proteins, including a number of
nonstructural(NS) proteins. One of the viral
proteases involved in this post-translational
processing is a heterodimericcomplex of the NS3
and NS4A proteins (NS3/NS4A).NS3 possesses the
proteolytic activity and NS4 is a membrane protein
that acts as a cofactor. Synthesis of new viral RNA
occurs in a highly structuredreplication complex
that consists of NS3, NS4A, NS4B, NS5A, and NS5B.
NS5B is an RNA-dependent RNA polymerase that is
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essential for viral replication. NS5A has a
presumptive role in the organization of the
replication complex and in regulating replication. It
is also involved in assembly of the viral particle that
is released from the host cell. Direct-acting
antivirals are inhibitors of the NS3/4A protease, the
NS5A protein, and the NS5B polymerase.
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Current hepatitis C treatments are made up
of combinations of drugs called direct-
acting antivirals (DAAs).DAAs directly
target the hep C virus in different ways to
stop it from making copies of itself and do
this so well that they promise a much
brighter future for people living with
hepatitis C. DAAs promise treatments with
shorter treatment times, much higher cure
rates, and fewer side effects.
There are four classes of direct-acting
antivirals that combine in different ways to
make up the different hep C DAA
treatments.
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1)NS3/4AProteaseInhibitors(PIs):- NS3/4A protease
inhibitors work by blocking a viral enzyme (protease)
that enables the hep C virus to survive and replicate
in host cells. Ex: glecaprevir, voxilaprevir .
2)Nucleosideand Nucleotide NS5B Polymerase
Inhibitors:- They directly target the hep C virus to
stop it from making copies of itself in the liver. They
attach themselves onto the genetic information, called
RNA, to block the virus from multiplying. Ex:-
sofisbuvir .
3)NS5A Inhibitors:-They block a virus protein, NS5A,
that HCV needs to reproduce and for various stages
of infection Ex:- ombitasvir,pibrentasvirand elbasvir.
4)Non-Nucleoside NS5B PolymeraseInhibitors:- They
work to stop HCV from reproducing by inserting
themselves into the virus so that other pieces of the
hep C virus cannot attach to it. Ex: Dasabuvir .
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Sofosbuvir
sold under the brand name Sovaldiamong
others, is a medication used for the treatment of
hepatitis C. It is only recommendedwith some
combination,simeprevir,ledipasvir, daclatasvir.
It is a prescription medicine used with other
antiviral medicines to treat adults with chronic
(lasting a long time) hepatitis C (HepC) with or
without cirrhosis (compensated).In those with
Hep C genotype (GT)1 or 4 infection, SOVALDI
is used in combination with peginterferon alfa
and ribavirin. In those with GT 2 or 3 infection,
SOVALDIis used in combination with ribavirin.
It is not known if SOVALDIis safe and effective
in adults who have had a liver transplant.
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Important Safety Information -
What is the most important
information I should know about
SOVALDI?
SOVALDIcan cause serious side effects,
including: Hepatitis B virus reactivation: Before
starting SOVALDItreatment,your healthcare
provider will do blood tests to check for
hepatitis B infection. If you have ever had
hepatitis B, the hepatitis B virus could become
active again during and after treatment with
SOVALDI.This may cause serious liver
problems, including liver
failure and death. If you are at
risk, your healthcare provider
will monitor you during and
after taking SOVALDI.
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MAVYRET:-
is a fixed-dose combination of
glecaprevir, a hepatitis C virus
(HCV) NS3/4A protease inhibitor,
and pibrentasvir,an HCV NS5A inhibitor, and is
indicated for the treatmentof patients with chronic
HCV genotype (GT) 1, 2, 3, 4, 5 or 6 infection
without cirrhosis and with compensatedcirrhosis
(Child-Pugh A). MAVYRETis also indicated for the
treatment of adult patients with HCV genotype 1
infection, who previously have
been treated with a regimen
containing an HCV NS5A
inhibitor or an NS3/4A protease
inhibitor, but not both. DOSAGE
FORMSAND STRENGTHS:
Tablets: 100 mg glecaprevir and 40 mg pibrentasvir.
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Contraindications : • Coadministration with
atazanavir and rifampin.
HowtheyWork?
Combination antiviral therapy helps prevent the
virus that causes hepatitis C from reproducing in the
body. Peginterferon and ribavirin often are
combined for treatment.A protease inhibitor or a
nucleotide analog inhibitor may be given along with
peginterferon and ribavirin or with ribavirin alone.
But some newer treatments do not use peginterferon
or ribavirin.
The length of your treatment depends on what
hepatitis C genotype you have. Genotypes 1 and 2
generally are treated for 12 weeks, and genotype 3
generally is treated for 12 or 24 weeks. If your viral
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load does not improve after initial treatment,a
different set of medicines may be used.
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Whentheyareused?
Combination antiviral therapy is prescribed
for people who have ongoing (chronic)
hepatitis C infection. It may be given to
people who have never had treatment or
when the first set of medicines has failed to
cure the infection.
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TreatmentSideEffectsgenerally:-
Hepatitis C drugs cause side effects, most commonly
a flu-like reaction that goes away after a few weeks.
Most of the side effects aren’t life-threatening.
However, it can be difficult to tolerate the side
effects for the full course of treatment,which lasts
from six months to a year. Being knowledgeable
about your treatmentand its side effects can help
you manage them.
The most common physical side effects from
hepatitis C drugs include:
fever
headache
muscle aches fatigue
nausea, vomiting, or diarrhea
dry mouth, thick saliva,
and mouth ulcers poor appetite
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While being treated for hepatitis C, it’s important to
be in good health. You should eat a well-balanced,
nutritious diet and make sure to drink plenty of
water to avoid dehydration.
Hepatitis C drugs may also cause side effects that
affect your mental health These include:
poor sleep or insomnia
anxiety
being irritable or short-tempered
low mood or depression Interferon stimulates
certain parts of the body, sometimes making it
difficult to sleep. Lack of good sleep and rest may
cause other problems such as anxiety, being short-
temperedor feeling sad.
Talk to your doctor about ways to improve your
sleep. Keeping a regular sleep schedule, learning
relaxation techniques, timing your medications, and
talking to others about how you’re feeling—both
physically and mentally—can help.
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OtherPotentialSideEffects
Treating hepatitis C can cause other side effects,
including:
Hair loss is common for those taking interferon.
Once treatment ends, your hair will grow back.
Skin rashes from ribavirin may come and go,
mainly on the body and arms. Cool baths and skin
lotions can help. You can reduce injection-site
reactions by changing the injection spot and
applying an ice pack. Talk to your doctor if you’re
concerned about these problems.
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When to Call Your Doctor Although it doesn’t
happen very often, hepatitis C drugs may cause
serious side effects. It’s important to learn what they
are so you can identify them and get immediate
medical help.
Seriousside effectsinclude:
chest pain
shortness of breath
vision changes
thyroid problems
Any of these side effects can be potentially serious.
Speak with your doctor about how you’re feeling
and don’t hesitate to go to the emergencyroom if
necessary.
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References:-
1-US Food and Drug Administration. Approval of
Victrelis (boceprevir) a direct acting antiviral drug
(DAA) to treat hepatitis C virus (HCV).
http://www.fda.gov/forconsumers/byaudience/forpat
ientadvocates/ ucm255413.(Accessedon August 1,
2013).
2- Sofosbuvir (Sovaldi) - Treatment - Hepatitis C
Online". www.hepatitisc.uw.edu. Retrieved8
January 2017.
3-FDA, News Release (June 28, 2016). "FDA
approves Epclusa for treatment of chronic Hepatitis
C virus infection".
