Page 361 - Review of Medical Microbiology and Immunology ( PDFDrive )

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PART IV Clinical Virology
350
Antibodies against HCV are made, but approximately
HCV proteins and does not include the highly variable enve-
75% of patients are chronically infected and continue to
produce virus for at least 1 year. (Note that the rate of
lope proteins. The test does not distinguish between IgM
and IgG and does not distinguish between an acute,
chronic carriage of HCV is much higher than the rate of
chronic, or resolved infection.
chronic carriage of HBV.) Chronic active hepatitis and
cirrhosis occur in approximately 10% of these patients. For
If the result of ELISA antibody test is positive, a poly-
patients who clear the infection, it is not known whether
of viral RNA (viral load) in the serum should be performed
reinfection can occur or whether there is lifelong
to determine whether active disease exists. Reduction of the
immunity. merase chain reaction–based test that detects the presence
viral load in patients with hepatitis C is used to monitor the
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success of drug therapy. Isolation of the virus from patient
Clinical Findings
specimens is not done. A chronic infection is characterized
The acute infection is often asymptomatic. If symptoms,
such as malaise, nausea, and right upper quadrant pain do
test, and detectable viral RNA for at least 6 months.
occur, they are milder than occur with infection by the
other hepatitis viruses. Fever, anorexia, nausea, vomiting,
Treatment
and jaundice are common. Dark urine, pale feces, and ele-
Treatment of acute hepatitis C with peginterferon alfa sig-
vated transaminase levels are seen.
nificantly decreases the number of patients who become
Hepatitis C resembles hepatitis B as far as the ensuing
chronic liver disease, cirrhosis, and the predisposition to
The treatment of choice for chronic hepatitis C is a com-
hepatocellular carcinoma are concerned. Note that a
bination of drugs from three classes: RNA polymerase inhibi-
chronic carrier state occurs more often with HCV infection
tors, NS5A inhibitors, and protease inhibitors (see Table 41–6).
than with HBV. Liver biopsy is often done in patients with chronic carriers.
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These drugs are administered orally which is an improve-
chronic infection to evaluate the extent of liver damage and
ment over the drugs in previous regimens that often included
to guide treatment decisions. Many infections with HCV,
pegylated interferon-alpha which is administered parenter-
including both acute and chronic infections, are asymp-
tomatic and are detected only by the presence of antibody.
able combination is Harvoni which is a combination of
The mean incubation period is 8 weeks. Cirrhosis resulting
sofosbuvir (RNA polymerase inhibitor) and ledipasvir (NS5A
from chronic HCV infection is the most common indica-
inhibitor). Another is Viekera which is a four-drug combina-
tion for liver transplantation.
tion: dasabuvir (RNA polymerase inhibitor), ombitsavir
HCV infection also leads to significant autoimmune
(NS5A inhibitor), paritaprevir (protease inhibitor) and rito-
reactions, including vasculitis, arthralgias, purpura, and
membranoproliferative glomerulonephritis. HCV is the
These drug combinations are very effective against genotype
main cause of essential mixed cryoglobulinemia. Cryo-
1, the most common type in the United States. Daklinza, a
globulins are defined by their ability to precipitate at
combination of sofosbuvir (RNA polymerase inhibitor) and
cold temperature (cryo = cold). The cryoprecipitates are navir (a booster of protease activity; see Chapter 35, page 276).
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daclatasvir (NS5A inhibitor) is effective against genotype 3
immune complexes composed of HCV antigens and
HCV. These various drug combinations offer the prospect of
antibodies.
a “cure” for chronic hepatitis C.
Laboratory Diagnosis
HCV infection is diagnosed by detecting antibodies to
There is no vaccine and hyperimmune globulins are not
HCV in an enzyme-linked immunosorbent assay (ELISA)
available. Pooled immune serum globulins are not useful
(see Table 41–5). The antigen in the assay is a recombinant
TABLE 41–5 Laboratory Test Results at Different Stages of HCV Infection
Diagnostic Test Acute HCV Infection Chronic HCV Infection Recovered from HCV Infection
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Positive
Antibody to HCV
Positive in 6–24 weeks. Negative
Positive
early in infection
Undetectable
Detectable
Detectable within 1–2 weeks
Viral Load
(HCV RNA in serum)
Transaminase
to near-normal
(alanine aminotransferase,
and fluctuate
ALT)
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