734
U N I T 8
Gastrointestinal and Hepatobiliary Function
routinely in blood. It appears before onset of symptoms,
peaks during overt disease, and then declines to unde-
tectable levels in 3 to 6 months. Persistence beyond 6
months indicates continued viral replication, infectivity,
and chronic hepatitis. HBeAg appears in the serum soon
after HBsAg and signifies active viral replication. IgM
anti-HBc becomes detectable shortly before the onset of
symptoms, concurrent with the onset of an elevation in
serum transaminases. Over the months, the IgM anti-
body is replaced by IgG anti-HBc. Anti-HBe is detectable
shortly after the disappearance of HBeAg and its appear-
ance signals the onset of resolution of the acute illness.
IgG anti-HBs, a specific antibody to HBsAg, occurs in
most individuals after clearance of HBsAg. Development
of anti-HBs signals recovery from HBV infection, non-
infectivity, and protection from future HBV infection.
Anti-HBs is the antibody present in persons who have
been successfully immunized against HBV.
The presence of viral DNA (HBV DNA) in the serum
is the most reliable indicator of HBV infection. It is tran-
siently present during the presymptomatic period and
for a brief time during the acute illness. The presence of
DNA polymerase, the enzyme used in viral replication,
usually is transient but may persist for years in persons
who are chronically infected.
Hepatitis B can be prevented by vaccination and by the
screening of donor blood, organs, and tissues. The vac-
cine, which is prepared from purified HBsAg produced in
yeast, induces a protective antibody response in 95% of
vaccinated infants, children, and adolescents.
3
The CDC
recommends vaccination of all children 0 to 18 years of
age as a means of preventing HBV transmission.
12
The
vaccine also is recommended for all unvaccinated adults
who are at high risk for infection, international travelers
to regions with high or intermediate levels of endemic
HBV infection, persons with human immunodeficiency
virus (HIV) infection, persons with chronic liver dis-
ease, injection drug users, and all other persons seeking
protection.
12
It is also recommended that all pregnant
women be routinely tested for HBsAg during an early
prenatal visit and that infants born to HBsAg-positive
mothers receive appropriate doses of hepatitis B immune
globulin (HBIG) and hepatitis B vaccine.
9
Hepatitis C.
The hepatitis C virus, discovered in 1989,
is a member of the
Flaviviridae
family. It is a small, envel-
oped, single-stranded RNA virus.
3,4
The virus is geneti-
cally unstable, giving rise to multiple genotypes and
subtypes. This allows a divergent population of closely
related variants to circulate in infected persons.
3
One
of the HCV envelope proteins, the E2 protein, which
is the target for anti-HCV antibodies, is the most vari-
able region of the entire viral genome. It is likely that
the wide diversity of genotypes contributes to the patho-
genicity of the virus, allowing it to escape the actions
of host immune mechanisms and antiviral medications,
and to difficulties in developing a preventive vaccine.
Hepatitis C is the most common cause of chronic
hepatitis, cirrhosis, and hepatocellular cancer in the
world.
3,4,13,14
Before 1990, the main route of transmission
of HCV was through contaminated blood transfusions
or blood products. With implementation of HCV testing
in blood banks, the current risk of HCV infection from
blood transfusion is almost nonexistent in the United
States and other developed countries. Currently, recre-
ational injection drug use is the most common mode of
HCV transmission in the United States.
13,14
Other risk
factors include needlestick injuries in health care settings
and birth to an HCV-infected mother.
13,14
In fact, the
risk from needle sticks is much higher than for human
immunodeficiency virus (HIV).
3
The incubation period for HCV infection ranges
from 2 to 26 weeks (average, 6 to 12 weeks).
3
Children
and adults who acquire the infection usually are asymp-
tomatic or have nonspecific signs and symptoms such
as fatigue, malaise, anorexia, and weight loss. A minor-
ity of persons develop sufficient elevations in bilirubin
to produce overt jaundice or the development of dark
urine. Only a few persons who are newly infected with
HCV will clear the infection, with the majority going
on to develop chronic hepatitis.
13–15
Factors associated
with spontaneous clearing of HCV infection appear
to include younger age, female sex, and certain histo-
compatibility genes. The most serious consequences
of chronic HCV infection are progressive liver fibrosis
leading to cirrhosis, and hepatocellular cancer.
Both HCV RNA and anti-HCV antibody tests are
available for detecting the presence of HCV infection
(Fig. 30-9). Unlike hepatitis A and B, antibodies to HCV
are not protective, but they serve as markers for the dis-
ease. With anti-HCV antibody tests, infection often can
be detected as early as 6 to 8 weeks after exposure, but
false-negative results can occur in immunocompromised
people and early in the course of the disease. Direct
measurement of HCV RNA in the serum can detect the
virus as early as 1 to 2 weeks after exposure with viral
tests that use polymerase chain reaction (PCR) methods
(see Chapter 14).
Hepatitis D and E.
Hepatitis D virus, or the delta hepa-
titis agent, is a defective RNA virus that requires con-
comitant infection with HBV for its own replication.
16
Symptoms
Anti-HCV
Exposure
ALT
HCV RNA
Months
Years
0 1 2 3 4 5 6
1 2 3 4 5 6
FIGURE 30-9.
The sequence of serologic changes in chronic
hepatitis C, with persistence of hepatitis C virus (HCV) RNA and
exacerbations and remissions of clinical symptoms indicated
by changes in serum alanine aminotransferase (ALT) levels.
