Research
Paper on Current developments in
Hepatitis C
Introduction
Prince and colleagues as post-transfusion non-A, non-B hepatitis
first described hepatitis C in 1974. Consequently, chronicity of
post-transfusion non-A, non-B hepatitis was discovered as a
blandly symptomatic disease with elevation of the liver enzyme
alanine aminotransferase (ALT) and chronic hepatitis seen on
liver biopsy. The infectious nature of the entity was confirmed
when the disease could be conveyed from humans to chimpanzees.
The etiologic agent, the hepatitis C virus (HCV), was recognized
as a genetic sequence in 1989 by Choo through random polymerase
chain reaction (PCR) assays in plasma of chimpanzees chronically
infected with non-A, non-B hepatitis, that led to the
development of a first-generation HCV antibody test that
identified HCV as the basis of majority cases of formerly
"diagnosed" non-A, non-B hepatitis.
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Current Treatment and Developments
Treatment against chronic hepatitis C includes interferon alfa
alone or in combination with ribavirin. Interferon alfa has
antiviral and immunomodulatory movement. The antiviral effects
are chiefly arbitrated by way of increase in intracellular 2'5'
oligoadenylate synthetase and protein kinase enzymes, which
restrain creation of viral compounds. Interferon also influences
the immune system by way of various mechanisms, for instance an
increased expression of HLA class I antigens on hepatocyte cell
membranes and the promotion of natural killer cell activity,
that simultaneously lead to the increased clearance of HCV-infected
hepatocytes. The way of action of ribavirin in fusion with
interferon is inadequately learned, but it may involve antiviral
activity via chain termination of HCV-specific RNA-dependent
RNA-polymerase or act as an immune modulator by changing the
anti-HCV immune response from a T helper 2 cell- dominated
response with humoral activity to a T helper 1 cell- -dominated
response, with predominantly cytotoxic activity (Lau, pp
1002-1009)
The greatest results in adults are currently obtained with an
admixture of-interferon plus ribavirin, for 6 or 12 months.
Sustained response can be achieved after 6 months of combined
therapy in 65-70% of patients with genotype 2 or 3. In patients
with genotype 1 and 4, and a high viral load (more than 2
million copies/ml), sustained replication is only 30-40% after12
months of treatment, barely better if the viral load is low. The
premonitory conditions for good response are age < 40 years,
female, genotype non-1, viral load, absence of cirrhosis (Davis,
pp 104-114).
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The side effects of interferon are
fever, fatigue, depression, weight loss, thrombopenia,
neutropenia, and hypothyroidism. Ribavirin may cause anemia.
Currently, promising results in adults have been published with
pegylated interferon that allows one-time weekly injections,
with development of the response rate as compared with
interferon, and better tolerance (Zeuzem, 2000). There is a
momentum to using a combination of Peg interferon and ribavirin.
In children, studies are finite, comprise small numbers of
patients, and use a monotherapy with interferon. The success
rate varies from 8 to 56%, with a mean at 40% that is better
than the altogether response rate to monotherapy in adults
(15-30%). The sequence is too small to estimate the role of
genotype or mode of contamination. None has been recognized
using a combination with ribavirin.
Vaccination against HCV is so far not obtainable,
notwithstanding intense efforts. The larger problems are the
high rate of mutation of HCV (quasi-species), with the
hypervariable region being the site of a principal
neutralization epitope, the delayed emanation of neutralizing
antibodies, the problems of establishing a favorable tissue
culture, and conditions of animal studies in chimpanzee.
Powerful cellular immune response is implicated in viral
clearance. The present developments include DNA-based
vaccination 20, chimeric viruses expressing HCV genes 21, or
viruslike particles.
The time of treatment for chronic hepatitis C with interferon
and ribavirin is 48 weeks in genotype 1 patients and 24 weeks in
genotype 2 and 3 patients. Treatment result is measured in terms
of HCV viral load, and a treatment response is described as
deprivation of perceptible plasma HCV RNA (< 50 IU/mL or < 100
copies/mL). An SVR is defined as undetectable HCV RNA 6 months
after the end of treatment.
There are three different outcomes of therapy:
1. End-of-treatment response, which is sustained through post
treatment month 6 (SVR)
2. End-of-treatment response with reversion of HCV viremia after
treatment is ceased, generally within first 12 weeks
(response-relapse)
3. HCV RNA still perceptible at the end of treatment and
generally correspondingly during treatment (non-response).
But once an SVR has been concluded at 6 months after treatment,
the patient can be contemplated cured of chronic hepatitis C.
Studies have shown that 6 years subsequent to an SVR following
interferon monotherapy, viral relapse occurred in 10% to 28% of
patients, even though these relapse patients protracted to have
usual ALT levels and showed minimum inflammation and no fibrosis
on liver biopsy. Also, none of the SVR patients developed
cirrhosis, liver decompensation, or HCC contrasted with a 30%
rate of such intricacy in non-responders. Liver-related death
rate after an average of 6 years was 0% in patients with a
sustained response contrasted with 2.2% in non-responders.
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By the overture of interferon plus ribavirin fusion therapy,
viral relapse following an SVR has become rare. Viral relapse
occurred in 0.8% of patients at post treatment year 1 and in
1.8% at year 2. At post treatment year 4, there was no more
viral relapse. (McHutchison, pp 24-34) Succeeding an SVR infra
any treatment, notable improvement of inflammation and
retraction of fibrosis are observed, and even the retraction of
cirrhosis has been reported in 49% of patients after successful
treatment. (Poynard, pp 1303-131)
An SVR is the best consequence of HCV therapy. Nonetheless,
there are still advantages of interferon-based HCV therapy,
indeed when the virus is not forever cleaned. Liver inflammation
ameliorates, and the rate of fibrosis progression is slowed (Alri
et. al, 2001 and Shiratori et. al, 2000). In a study by
Shiratori and colleagues fibrosis advancement utilizing the
METAVIR fibrosis score (0-4) was collated betwixt:
HCV patients who had a sustained response
Patients who had treatment but had no viral response
Patients who did not had any treatment.
Subsequently, after more than 3 years of follow-up, fibrosis
change was -0.88 in the SVR group, +0.15 in the nonresponse
group, and +0.59 in the no treatment group. Clinically, when
collated with no treatment, interferon-based monotherapy in
content HCV-related cirrhosis, that are majorly without viral
clearance, has been analogous with a reduced rate of progression
to decompensation or HCC and reduced mortality (Nishiguchi, pp
196-97)
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