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THE CASE
A 45 years old Egyptian gentleman known case of diabetes mellitus
and hypertension for 6 years.
His laboratory workup showed normal CBC, Urea and Electrolytes &
INR.
Mildly elevated transaminases however normal bilirubin and albumin.
No SVR achieved.
INTRODUCTION
Chronic hepatitis C virus (HCV) infection is one of the most common
chronic liver disease and accounts for 8000 to 13,000 deaths each
year.
The majority of liver transplants performed in the United States are
for chronic HCV.
Globally, it was estimated that in 2005, more than 185 million people
had hepatitis C virus (HCV) antibodies (prevalence of 2.8 percent).
The existence of hepatitis C originally identifiable only as a type of
non-A non-B hepatitis was suggested in the 1970s and proven in
1989.
STRUCTURE
Hepatitis C virus (HCV) is a small (5565 nm in size),
enveloped, positive-sense single-stranded RNA virus of the
family Flaviviridae.
The hepatitis C virus particle consists of a core of RNA, surrounded by
an icosahedral protective shell of protein, and further encased in a
lipid envelope of cellular origin.
INTRODUCTION
INTRODUCTION
REPLICATION
The virus replicates mainly in the hepatocytes, where it is estimated
that daily each infected cell produces approximately fifty virions
(virus particles) with a calculated total of one trillion virions
generated.
HCV has a wide variety of genotypes and mutates rapidly due to a
high error rate on the part of the virus' RNA-dependent RNA
polymerase.
The mutation rate produces so many variants of the virus it is
considered a quasispecies rather than a conventional virus species.
Entry into host cells occur through complex interactions between virions
and cell-surface molecules.
The NS proteins then recruit the viral genome into an RNA replication
complex, which is associated with rearranged cytoplasmic membranes.
INTRODUCTION
TRANSMISSION
Most patients infected with HCV in the United States and Europe
acquired the disease through intravenous drug use or blood
transfusion, the latter of which has become rare since routine testing of
the blood supply for HCV was begun in 1990.
NATURAL HISTORY
Acute infection
Hepatitis C infection causes acute symptoms in 15% of cases which
are mild and vague, including a decreased appetite,
fatigue, nausea, muscle or joint pains, and weight loss.
Chronic infection
DIAGNOSIS
There are a number of diagnostic tests for hepatitis C, including
HCV antibody enzyme immunoassay or ELISA, and quantitative
HCV RNA polymerase chain reaction (PCR).
HCV RNA can be detected by PCR typically one to two weeks after
infection, while antibodies can take substantially longer to form and
thus be detected.
TREATMENT
A greater understanding of the hepatitis C virus (HCV) genome and
proteins has enabled efforts to improve efficacy and tolerability of
HCV treatment.
Notably, this has led to the development of multiple direct-acting
antivirals (DAAs), which are medications targeted at specific steps
within the HCV life cycle.
DAAs are molecules that target specific nonstructural proteins of the
virus and results in disruption of viral replication and infection.
There are four classes of DAAs, which are defined by their mechanism
of action and therapeutic target. The four classes are nonstructural
proteins 3/4A (NS3/4A) protease inhibitors (PIs), NS5B nucleoside
polymerase inhibitors (NPIs), NS5B non-nucleoside polymerase
inhibitors (NNPIs), and NS5A inhibitors
NS5A inhibitors
NS5B nucleotide
polymerase
inhibitors (NPI)
NS5B nonnucleoside
polymerase
inhibitors (NNPIs)
NS3/4A protease
inhibitors
Daclatasavir (DCV)
Sofosbuvir (SOF)
Dasabuvir (DSV)
Simepravir (SMV)
Elbasvir (EBR)
Paritapravir (PTV)
Ledipasvir (LDV)
Grazoprevir (GZR)
Ombitasvir (OBV)
Boceprevir (BOC)
Velpatasvir (VEL)
Telaprevir (TVR)
Regimen
HCV Genotype
1a
1b
5 or 6
SOF + PR
12 wks
12 wks
12 wks
SMV + PR
Not
recommended
LDV/SOF
12 wks, no RBV
12 wks, no RBV
Not recommended
Not
recommended
Not recommended
12 wks + RBV
Not
recommended
SOF + SMV
12 wks, no RBV
12 wks, no RBV
Not
recommended
SOF + DCV
12 wks, no RBV
12 wks, no RBV
12 wks, no RBV
OBV/PTV/RTV
+ DSV
OBV/PTV/RTV
12 wks
+ RBV
12 wks,
no RBV
Regimen
HCV Genotype
1a
1b
5 or 6
SOF + PR
12 wks
12 wks
12 wks
SMV + PR
Not recommended
LDV/SOF
Not recommended
Not recommended
Not recommended
24 wks + RBV
Not recommended
SOF + SMV
Not recommended
SOF + DCV
OBV/PTV/RTV
+ DSV
OBV/PTV/RTV
24 wks
+ RBV
12 wks
+ RBV
No Cirrhosis
Regimen
Compensated Cirrhosis
(Child-Pugh A)
GT2
GT3
GT2
GT3
SOF + PR
12 wks
12 wks
12 wks
12 wks
SOF + RBV
12 wks
24 wks
16-20 wks
Not
recommended
SOF + DCV
12 wks,
no RBV
12 wks,
no RBV
12 wks,
no RBV
24 wks
+ RBV
REFERENCES
Uptodate
Medscape
EASL/AASL guidelines
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