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A 49-year-old man comes to your office, requesting
testing for hepatitis C. He recently attended his 25-
year college reunion, where he heard from a mutual
acquaintance that an old friend was seriously ill with
cirrhosis due to hepatitis C. The patient became very
concerned because he had œpartied with this friend
during a brief period of experimentation with injection
drugs while in college. The patient is otherwise
healthy and denies any symptoms except for occasional
fatigue after a long day at work. Physical examination
of the patient is unremarkable. There are no
stigmata of chronic liver disease.
Which of the following is the most appropriate
course of action?
A) Check a quantitative HCV PCR (œviral load).
B) Order a recombinant immunoblot assay (RIBA).
C) Order an HCV antibody test (enzyme immunoassay).
D) Order a qualitative HCV PCR.
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The patient returns several weeks later to discuss his
test results. His HCV test is positive. A liver
panel obtained that day shows an ALT of 48 IU/L
(normal range, 0“20) and an AST of 39 IU/L (0-31).
His albumin and total bilirubin are within normal limits.
He is extremely anxious about his liver, as he has
been in contact with his old college friend and learned
that his friend is now on the waiting list for a liver
transplant.
You now recommend:
A) Liver-spleen scan to assess for evidence of cirrhosis.
B) Reassuring the patient that his mild liver test
abnormalities rule out cirrhosis.
C) Percutaneous liver biopsy.
D) Abdominal ultrasound with Doppler to assess for
evidence of cirrhosis.
E) Abdominal CT to assess for evidence of cirrhosis
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The patient agrees to the test. Nonetheless, he is still
very concerned about his situation and asks what you
think the chances are that he already has cirrhosis.
Regarding the development of progressive liver
disease in hepatitis C, all of the following are
true EXCEPT:
A) Approximately 20% of patients with chronic HCV
infection will develop serious liver disease.
B) Heavy alcohol use is a risk factor for development
of serious liver disease.
C) Acquisition of HCV infection after the age of
40 is associated with increased risk of developing
serious liver disease.
D) HVC genotype impacts on the probability of
developing end-stage liver disease.
E) Males are more likely than females to develop
serious liver disease.
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The patient is concerned that he may transmit the
virus to his wife or children. They are tested and are
found to be negative for HCV infection. He is relieved
but asks for advice to prevent infecting them.
You tell him all of the following EXCEPT:
A) No change in sexual practices is recommended for
couples in a long-term monogamous relationship
in which one partner is HCV+ and the other
HCV“.
B) The use of condoms is recommended for couples
in a long-term monogamous relationship in which
one partner is HCV+ and the other HCV“.
C) Hepatitis C is not spread by hugging, sneezing, or
sharing a drinking glass.
D) Household members of persons infected with
HCV should not share items that might be contaminated
with small amounts of blood, such as
razors or nail clippers.
E) Parenteral exposure to infected blood is a major
route of transmission of hepatitis C.
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The patient™s liver biopsy shows mild to moderate
inflammatory activity and portal and periportal fibrosis
(Stage 2). He is relieved to find out that he does not
have cirrhosis, but remains very concerned about his
hepatitis and wants to do everything possible to œget
rid of the hepatitis C. He asks about treatment for
his HCV.
You tell him which of the following?
A) Combination therapy with interferon and ribavirin
results in sustained virologic responses (SVR) in
40“70% of patients treated.
B) Failure to attain a 2-log10 drop in the quantitative
HCV PCR in the first 12 weeks of antiviral treatment
is a predictor of treatment failure.
C) Combination therapy with interferon and ribavirin
can cause numerous side effects, including cytopenias,
flu-like symptoms, worsening of autoimmune
conditions, depression, and hemolytic anemia.
D) The HCV genotype is a strong predictor of response
to treatment.
E) All of the above.
F) A and C
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All of the following are significant side effects of
interferon therapy for hepatitis C EXCEPT:
A) Depression.
B) Hypoglycemia.
C) Aggression and homicidal behavior.
D) Myalgias.
E) Leukopenia.
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1
The correct answer is C. The sensitivity and specificity
of the present-day HCV antibody test are excellent;
thus, this is the best test to perform in this situation.
Rarely, patients with immunologic impairment, such
as HIV infection, have HCV viremia without detectable
antibody, but this would not be a concern in this
otherwise healthy patient. Quantitative HCV PCR is
not a reliable means for diagnosing HCV infection
because currently used methods are insensitive at low
levels of viremia; thus, infection cannot be ruled out by
the finding of a level of HCV below the lower limit of
detection of the test. The RIBA was developed as a
confirmatory test at a time when the specificity of firstline
antibody tests was suboptimal. Because of the
improved specificity of present-day antibody testing,
the RIBA is now rarely used. Qualitative HCV PCR
is the most sensitive test for the presence of HCV
RNA, with a limit of detection that is lower than that
of quantitative PCR. It is useful to establish the presence
of viremia, but is more expensive than antibody
testing and thus not a first-line test.
2
The correct answer is C. Having established that the
patient has hepatitis C with elevated liver enzymes,
the next step is to determine the severity of his liver
disease. Although his liver function is reassuring, it
does not exclude the possibility of advanced fibrosis
or even well-compensated cirrhosis. Although the
argument has been made that not all patients with
chronic hepatitis C require liver biopsy , it is the only
direct means to evaluate the extent of liver injury.
HELPFUL TIP: There is some controversy
as to whether or not checking liver enzymes is
considered adequate screening for hepatitis C.
Patients with normal liver enzymes are unlikely
to progress to severe liver disease
despite the presence of hepatitis C. However,
since decisions about treatment in patients
with a persistently normal ALT need to be tailored
to the individual, most experts now recommend
hepatitis C antibody testing as a screening test
3
The correct answer is D. While only a minority of
persons infected with HCV develop serious liver disease,
the likelihood of progression is difficult to predict
in an individual patient. Nonetheless, male sex,
heavy alcohol use, and acquisition of HCV infection
after age 40 are associated with increased risk of progressive
liver disease, while viral load and genotype
are not.
4
The correct answer is B. HCV is spread by parenteral
contact with infected blood. In contrast to hepatitis B,
sexual transmission of HCV is inefficient and appears
to be a minor route of spread. Thus, it is not recommended
that couples in long-term monogamous relationships
alter their sexual practices (e.g., use of condoms,
etc.). For persons not in monogamous relationships,
condom use is recommended.
5
The correct answer is E. Combination therapy with
interferon and ribavirin is the standard treatment of
HCV. The HCV genotype is a major factor in determining
the likelihood of achieving sustained virological
response (SVR) (although not the likelihood of
progression to end-stage liver disease), with genotype
1 (including 1a and 1b) being the most difficult to
clear, while genotypes 2 and 3 are the most responsive
to treatment. Stage of fibrosis is also a factor, with
patients with stages 3 and 4 (bridging fibrosis and cirrhosis)
being less likely to achieve SVR. Higher baseline
viral levels also tend to predict poorer response to
treatment. Decreases in viral levels of < 2-log10 after
12 weeks of treatment are predictive of lack of response
to therapy. Combination therapy is expensive
and is associated with significant toxicities. The major
concerns with ribavirin are hemolytic anemia and teratogenicity,
while the interferons (standard or the
long-acting pegylated forms) have a long list of potential
side effects, of which neuropsychiatric problems
such as depression and irritability are often the most
troublesome.
6
The correct answer is B. Interferon therapy is fraught
with adverse effects, including those listed above. Flulike
symptoms of myalgias, malaise, fever, chills, headache,
and weight loss are particularly common
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