Review
Article
ROLE OF MODERN
TECHNOLOGY FOR TREATMENT OF HCV
*MUSHTAQ U,
MUSHTAQ S, AFZAL M, ALI Q, MALIK A
Institute of
Molecular Biology and Biotechnology, University of Lahore, Lahore, Pakistan
Corresponding
author email: sairamushtaq34@gmail.com, saim1692@gmail.com
(Received, 5th February 2020, Accepted 29th
March 2020)
Abstract: HCV is the main reason of the liver
disease and worldwide it is one of the major issues of health due to its
development into cirrhosis, failure and cancer of liver. The transference of
HCV is mainly through the parental but people who use drug like intravenous are
also at greatest threat. The life cycle of HCV is now understood in a more
precise way due to extensive studies. Due to more understanding of this virus
there is establishment of more effectual antiviral medications and also
diagnostic devices. Test of nucleic acids are suggested for the validation of
active HCV. Serology tests are suggested for the groups that are at the
greatest risk. Earlier for the standard medications of HCV interferon (IFN-a)
and ribavirin are used. Later FDA approved a number
of drugs such as harvoni, simeprevir
and boceprevir etc. for the proper treatment of HCV. Antiviral
medications will be utilized to treat the infections of HCV. In the management
of certain severe viral infection, therapeutic option has improved in a better
way. There is need of follow-up and careful consideration as well as there are
many new technologies that have developed for the quantitative measurement of
viral genome concentration in the body fluid of patients. Initially this
measurement led to important insight in the viral infection pathogenesis as
well as these test also revolutionized natural history of HCV. In addition
viral load test are pure tool for research, these are used in routine viral diagnosis.
Viral load test are used in clinical virology for diagnosis and prognosis of
patient’s.
Keywords: HCV, liver, ribavirin, cirrhosis, drug, cancer, interferon
Introduction
HCV
belongs to flaviviridae family and enveloped in a
membrane and its genus is hepacivirus. The RNA of HCV
is single stranded and its polarity is positive. HCV result in a disease that
is known as hepatitis C that is a disease of liver (Bacon,
2002; Davis, 2002). There are two
types of hepatitis C that are caused by HCV. One is acute and second one is
chronic. Time span of acute hepatitis C is shorter and it causes very less or
almost no sign and symptoms. In majority of the cases infection of acute one get
better without any need of treatment. There are main five kinds of viruses of
hepatitis that result in acute one. It can also leads towards chronic hepatitis
that is a lifelong sickness or disease (Conry-Cantilena et al., 1996; Di Bisceglie and
Hoofnagle, 2002). People that
are infected with HCV, their disease can progress into cirrhosis in which liver
could not work accurately and can also develop into cancer of liver (Association,
1995; Berger and Preiser,
2002). The number of patients that are recognized every year with the
infection of hepatitis C virus are approximately four million. Approximately
170 million people of the world are affected with HCV. At present time there is
no vaccine exist that is effective for the treatment of HCV. HCV is the related
to Hepatitis C virus. It is a major cause of liver cancer, hepatocellular
carcinoma and liver failure (Alberti
et al., 2002; Alter et al., 1999; Berger et al., 2001). This infection
spread through blood by drug used injection, drug transfusion of blood product
and by sexual practices which cause blood exposure. Chronically infected people
will be affected by liver cancer or cirrhosis. It is not spread through food,
water and breast milk (Briggs
et al., 2001; Conry-Cantilena et
al., 1996).
There are two
stages of HCV one is acute and other is chronic. On the basis of stage of the
infection there is variation in signs and symptoms. The symptoms of HCV are
vomiting, fever, fatigue, dark urine, poor appetite, jaundice, itchiness on skin, loss in weight and severe pain in joints.
The spreading of hepatitis C occurs when blood that is infected with the virus
of hepatitis c enter into the bloodstream. It enters either through blood that
is contaminated or body fluids of a person that has the disease (Control
and Prevention, 2001; Di Bisceglie, 2000; Eddy, 1996). Virus of
hepatitis is not spread through bites of mosquito, coughing, sneezing and using
eating utensils of an infected person. Due to variation in the genotypes of the
patients, there is differentiation in the response towards interferon because
genotype is very important aspect. The clinical trials show the significance of
the genotypes of HCV due to difference in the response of alpha interferon.
More reaction is shown from the patients who have genotype 2 & 3 as
contrast to the patients who have genotype 1. SVR response that is shown by
genotype 2 & 3 is more as compare to the response that is shown by the
genotype 1 (El-Zayadi
et al., 2005; Fried et al., 2002; Preiser et al., 2000).
Labortary Testing
There
are three classes of assays that are serologic assay, molecular assay and
genotype assay.
Serologic Assays
It detect
particular antibody to anti HCV. By using immunoassay, anti HCV detect in the
plasma or serum. By the US food and drug administration, two enzyme immune assays
are Abbott HCV EIA 2.0 and ORTHO HCV version 3.0 ELISA, as well as one enhanced
CHEMILUMINESCENCE immune assay (CIA). The particularity of present EIAs is
greater than 99%. When we perform test among those people having low prevalence
of hepatitic C, false positive result occurred (Table
1). False negative result occurs in severe immuno
separation i.e., solid organ
transplant recipient, infection with HIV or in patients having hemodialysis (Hodinka,
1998; Hoofnagle, 2002; Hu and Tong, 1999; Preiser et al., 2000).
Table 1: Tools for the diagnosis of hepatitis C
virus infection and hepatic fibrosis stage
Assay/Manufacturer |
Methods |
Reaction sample volume (µL) |
Lower limit for detection (lµ/mL) |
Instruments |
IVD registration |
References |
APTIMA HCV RNA
Qualitative Assay, Hologic-Gen-Probe |
TMA |
500 |
5.3 |
Not automated,
PANTHER System’s functionality currently in development |
FDA |
|
COBAS AmpliPrep/COBAS, TaqMan HCV
Qualitative Test v2.0, Roche Molecular System |
Real-time
RT-PCR |
650 |
15 |
Fully
automated: cobas p 630 Instrument (Primary Tube
Handling), COBAS AmpliPrep (Extraction and MM
setup), COBAS TaqMan Analyzer or the COBAS TaqMan 48 Analyzer (Amplification and detection) |
CE, FDA |
|
VERSANT HCV
RNA Qualitative Assay, Siemens |
TMA |
50 |
5.3 |
TMA modules
(TCS, Iuminometer HC+, etc.) |
CE, FDA |
|
COBAS AmpliPrep/COBAS AMPLICOR HCV Test v2.0, Roce Molecular Systems |
Real-time
RT-PCR |
250 |
50 (Plasma) 60
(seum) |
COBAS AmpliPrep (Extraction), COBAS AmpliPrep/COBAS
AMPLICOR Analyzer (Amplication and detection0 |
CE, FDA,
Canada |
|
COBAS AmpliPrep/COBAS AMPLICOR HCV Test v2.0, Roce Molecular Systems |
Real-time
RT-PCR |
500 |
50 (Plasma) 60
(seum) |
COBAS AmpliPrep/COBAS AMPLICOR Analyzer (Amplication
and detection0 |
CE, FDA, Japan |
Molecular assay
It detects
nucleic acid of virus. This is a qualitative assay and more sensitive then
quantitative assay. The availability of transcription mediated amplification
assay and polymerase chain reaction based assay, has reduce the need of
qualitative assay (Fried,
2002; Gross et al., 1994; Hodinka, 1998).
Genotype Assay
It is usually
done in clinic study and epidemiological studies determining the therapy. There
are six major genotype of HCV. Genotype 1 is followed by genotype 2 and 3. Genotype
1 is the most common in US. Genotype 4 and 6 are among less common genotype due
to its growing culture in United States (Berger
and Preiser, 2002; El-Zayadi et al.,
2005; Fattovich et al.,
2004).
Treatment of HCV
The
standard treatment for hepatitis C is direct acting antiviral (DAAs).
DAAs
DAAS acts on
various targets in HCV virus. Some drugs has not
function alone, but they perform their activity by combining them with other
drugs. DAAs drug combination is prescribed for 12-24 weeks, once or twice a day
by oral pathway. DAAS drug combination is not injected in patients. Sometimes
they are in single tablet as they are very effective. In some instance DAAs
drug combination is prescribed for only 8 week to those patients that are not
suffering from liver disease (Berger
et al., 2001; Fattovich et al.,
1997; Feld and Hoofnagle,
2005; Hadziyannis et al.,
2004). Except old treatment (DAAs) directly effect on hepatitis C virus.
Side effects of DAAs are headache, vomiting
and fatigue.
There are various
mechanisms to fight HCV. These include,
Protease Inhibitors
The protease
inhibitors for hepatitis C are Simeprevir and Voxilaprevir. These DAAs block the enzyme protease and stop
the replication (Feld
and Hoofnagle, 2005; Hadziyannis et al.,
2004).
Polymerase Inhibitors
It stops the
replication ability of virus. Doctors use sofosbuvir
by combining it with other medicines for the treatment of hepatitis C (Gerlach
et al., 2003; McQuillan et al.,
1999; Pawlotsky, 2002).
There is a
protein that has important role in replication of hepatitis C , NS5A protein
that is directly target by NS5A inhibitors are Daclatasvir,
Elbasvir, Velpatasvir, Ombitasvir and Pibrantasvir (Pawlotsky
et al., 1998; Schreiber, 1996; Shah and Wong, 2006).
Ribavirin
When
ribavirin combine with peginterferon
alpha.
It can cause common side effects that are tiredness, headache, shivering, mood
changing, trouble sleeping, heart attack, liver problem, depression and pneumonia.
When we stop this treatment, it leads to weight gain. For the treatment of
hepatitis C, Doctor use ribavirin,
interferon. Ribavirin also stops the replication of
hepatitis C in the body. It has no function alone, people use it with
combination of other medications e.g. interferon. Drug has serious black box varining from the food and drug administration (Hadziyannis
et al., 2004; Hu and Tong, 1998; McQuillan et al.,
1999).
Interferon
Interferon is
natural proteins that increase immune activity in body. When we use interferon
for the treatment of hepatitis C, it lead to flu like symptoms and other side
effects are chills, headache, muscle aches, loss of appetite, changes in mood, anemia,
changes in vision, decreased thyroid function, depression and anxiety. When we
combine interferon with ribavirin then it cause lowering
in red blood cells (Hoofnagle,
2002; Kamal et al., 2004; Woolf and Sox, 1991).
Management
People who are
suffering from HCV can manage their symptoms by following guidelines are to
maintain body weight, avoid smoking, avoid alcohol and liver damaging
substances. There is no vaccine exists for HCV (Hoofnagle
and Seeff, 2006; Pawlotsky et al.,
1998).
Rate
During 2017, HCV
affected 71 million persons and estimated 19 people were diagnosed with chronic
infection of HCV. At the end of 2017, 5 million were treated by DAAS. There
should be more research and work on HCV to achieve 80% HCV by 2030 (Hoofnagle,
2002; Shah and Wong, 2006).
Future
Perspective
In last five
years there are many advancements have been done in the treatment of hepatitis
C disease. For the treatment of chronic type of hepatitis C there are many new
strategies that are under clinical phase. Much advancement has been done in the
dose and time span of the current treatments. Higher rates of SVR are obtained
when ribavirin is provided at higher levels. It is
observed when a small trial is conducted (Hofer
et al., 2003; Hu and Tong, 1999). Latest types of interferon are under clinical trials and
being tested. There is development of inhibitors (small molecules) that target
the enzymes and these enzymes are virally encoded like proteases (Kim,
2002; Pawlotsky,
2002).
Conclusion
The medications that are currently available for the
treatment of chronic form of HCV infection are interferon and ribavirin. Various side effects are related to these types
of treatments. Latest therapeutic strategies are under development and
inhibitors of HCV are focused in latest clinical trials. The rates of mortality
& morbidity are decreased due to advancements in the treatments of HCV. The
positive outcome is obtained from inhibitors of protease that are under initial
trials. There
are six main types of genotypes (1-6) of this virus and the divisions of these
genotypes vary globally. Response rates of these six genotypes have been
improved due to the advancement in the treatment.
Conflict of interest
The authors
declared the absence of any conflict of interest.
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