Viral Hepatitis C: Lab Diagnosis, Differential Diagnosis

Excerpt from "Viral Hepatitis C"
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Laboratory Diagnosis

1-Serological tests for HCV specific antibodies.
a)(EIA). Enzyme Immuno Assay.

HCV has multiple antigen proteins. Serological testing for these proteins
forms the basis for demonstrating the infection. The first test consisted
of enzyme immunoassaying for one protein, c100-3 (EIA-1).Assaying
for multiple antigen by same enzymatic method improved sensitivity to
94-100% and specificity to 97%.

False negative results were seen in:
-- patients tested before seroconversion ( before developing antibodies
    to HCV antigens)
-- immunosuppressed patients (HIV, organ transplants).
--viral heterogeneity (viral mutant different than USA pre{*filter*}
    virus (type 1a).
False positive results were seen in:
--hypergammaglobulinemia.
--connective tissue disorders.

b) (RIBA). Recombinant Immuno Blot Assay.

It is performed on a cellulose strip. Four HCV antigens are blotted
and reacted with patient's sera. Reactivity in at least 2 bands (RIBA-2)
indicate positive results which are obtained in 85% of patient infected
with HCV.

2-Direct demonstration of HCV RNA by PCR.
The viral RNA from whole {*filter*} ,serum, plasma, fixed tissues, is
converted to complimentary DNA (cDNA) by reverse transcriptase
and then amplified by PCR. This is a highly sensitive and highly specific
confirmatory test. There are ,however false negative but not false positive
results. The test is especially useful to monitor the effectiveness of the
interferon treatment. For this purpose:

3-Quantification of HCF RNA has been developed. The test results
could separate responders from non-responders to treatment.

4-Determination of HCV genotypes will also help in the determination
of aggressivnes, possible outcome and management of the infection.
There are conflicting reports as to which genotype is more aggressive
and which is more benign. It seems that type 1b is more aggressive
responding less to interferon therapy and requiring more liver transplants,
type 2 seems to be more benign and responds better to interferon
treatment. This test with serology and morphology will have a determining
place in the management of hepatitis C.

Differential Diagnosis

There are two conditions that can be confused with hepatitis C:
1-- Autoimmune chronic active hepatitis.
2-- {*filter*}ic liver disease.

Instances have been reported of patients who were treated with
alpha-interferon for hepatitis C without any result and responded
dramatically to cortisone therapy indicating presence of an autoimmune
hepatitis. According to a most recent report from Germany"distinction
between autoimmune liver disease and viral hepatitis C could be made
reliably on clinical and laboratory grounds and----a link between hepatitis
A, B, or C virus infection and autoimmune liver diseases is high unlikely".
(Lohse et al, Zeitschrift fur Gastr. 33(9):527-33,1995).In case of doubt
it is better to try first treatment with cortisone than with alpha-interferon.
{*filter*} seem to aggravate hepatitis C, actually "patients with hepatitis
C who develop cirrhosis under age 50 are those who consume {*filter*}
daily". (Bader, Viral hepatitis, page 141, H&H publishers, 1994).Thus,
patients with {*filter*}ic liver disease should be tested for hepatitis C
especially if rapid deterioration of the "{*filter*}ic" cirrhosis is observed.

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