C h a p t e r 3 0
Disorders of Hepatobiliary and Exocrine Pancreas Function
735
Acute hepatitis D occurs in two forms: coinfection
that occurs simultaneously with acute hepatitis B, and
a superinfection in which hepatitis D is imposed on
chronic hepatitis B.
3,16
The delta agent often increases
the severity of HBV infection.
The routes of transmission of hepatitis D are similar
to those for hepatitis B. In the United States, infection is
restricted largely to persons at high risk for HBV infec-
tion, particularly injecting drug users. The greatest risk
is in HBV carriers; these persons should be informed
about the dangers of HDV superinfection. Hepatitis D
is diagnosed by detection of antibody to HDV (anti-
HDV) in the serum or HDV RNA in the serum. There is
no specific treatment for hepatitis D. Because the infec-
tion is linked to hepatitis B, prevention of hepatitis D
should begin with prevention of hepatitis B through
vaccination.
The hepatitis E virus is an enveloped, single-stranded
RNA virus. It is transmitted by the fecal–oral route and
causes manifestations of acute hepatitis that are similar
to hepatitis A. It does not cause chronic hepatitis or the
carrier state.
3
A distinguishing feature of HEV infection
is the high mortality rate (approximately 20%) among
pregnant women, owing to the development of fulmi-
nant hepatitis. The infection occurs primarily in devel-
oping coutries of the world. The only reported cases in
the United States have been in persons who have recently
been in an endemic area.
Chronic Viral Hepatitis.
Chronic hepatitis is defined
as a chronic inflammatory reaction of the liver, or posi-
tive viral serologies of more than 6 months’ duration.
Chronic viral hepatitis is the principal cause of chronic
liver disease, cirrhosis, and hepatocellular cancer in the
world and now ranks as the chief reason for liver trans-
plantation in adults.
17
Of the hepatotropic viruses, only
three are known to cause chronic hepatitis—HBV/ HDV
and HCV. In both HBV and HCV, fibrosis and clini-
cal manifestations of chronic disease result from host
immune responses directed against viral antigens. In
response to these viral antigens, the host immune system
directs cytoxic T lymphocytes and cytokines to inhibit
viral replication (Chapter 15), the effects of which
induce inflammation and liver injury.
There are several treatment options for chronic viral
hepatitis. Drugs used in the treatment of chronic hepati-
tis B include the recombinant human interferon-2
α
and
peginterferon or nucleotide analog antiretroviral agent.
Persons with active viral replication may be treated with
recombinant human interferon-2
α
and peginterferon.
Peginterferons were developed by adding a polyeth-
ylene glycol (PEG) moiety to an interferon molecule
(PEG-IFN), resulting in a prolonged serum half-life and
the ability to administer the compound once weekly.
Nucleoside and nucleotide analogs (e.g., entecavir,
tenofovir) have shown good efficacy and better toler-
ance and may be used instead of interferon for treat-
ment of chronic HBV infection.
18
The current treatment
for persons with chronic hepatitis C is a combination of
peginterferon (alfa-2b or alfa-2a) plus ribavirin (a nucle-
oside analog), plus sofosbuvir (a polymerase inhibitor)
or sofosbuvir plus ribavirin.
19
Treatment for HCV is
70% to 80% effective, but is costly and has side effects.
These side effects range from flulike symptoms, which
are almost universal, to more serious and less common
side effects, such as psychiatric symptoms (depression,
anxiety), thyroid dysfunction, and bone marrow sup-
pression. Although most persons with HCV infection
are candidates for treatment, many have other health
problems that are contraindications to therapy.
Liver transplantation is a treatment option for those
with advanced decompensated cirrhosis from viral hepa-
titis. Liver transplantation, however, is not a cure for viral
hepatitis, as it often reoccurs in the transplanted liver.
Autoimmune Hepatitis
Autoimmune hepatitis is a chronic and progressive form
of hepatitis of unknown origin that is associated with
high levels of serum immunoglobulins, including auto-
antibodies.
3,4,20
Although the disorder is usually seen in
young women, it can occur in either sex at any age.
Clinical and laboratory observations have led to the
hypothesis that autoimmune hepatitis is a multifactorial
disorder, with genetic and environmental factors playing
important roles. Most knowledge about the genetics of
the disease has focused on the human leukocyte antigen
(HLA) genes that reside in the major histocompatibil-
ity complex (MHC), located on the short arm of chro-
mosome 6 (see Chapter 15). The environmental agents
assumed to induce autoimmune hepatitis are viruses,
immunizations, herbal products such as black cohash,
and medications such as minocycline, methyldopa, ator-
vastatin, simvastatin, interferons, and nitrofurantoin.
3,20
Autoantibodies, in particular antinuclear antibody and
anti–smooth muscle antibody, have been found in serum
of those with autoimmune hepatitis, although the exact
function of these antibodies in this condition is unknown.
Two distinct types of autoimmune hepatitis have
been broadly identified based on the presence of circu-
lating antibodies.
2,4,20
Type I autoimmune hepatitis, the
most common form of the disease, is characterized by
increased levels of anti–smooth muscle and antinuclear
autoantibodies. Approximately 30% of cases occur in
women younger than 40 years of age, a third of whom
have other autoimmune diseases.
4
Type II autoimmune
hepatitis, a rare disorder, occurs mainly in children 2 to
14 years of age and is characterized by the presence
of antibody to liver and kidney microsomes and liver
cytosol.
4
The disorder is often accompanied by other
autoimmune disorders, especially type 1 diabetes mel-
litus and thyroiditis. The genetic component for this
type of autoimmune hepatitis is less well defined than
for type 1.
Clinical manifestations of the disorder cover a spec-
trum that extends from no apparent symptoms to the
signs of liver failure. Physical examination may reveal no
abnormalities, but may also reveal hepatomegaly, sple-
nomegaly, jaundice, and signs and symptoms of chronic
liver disease. In asymptomatic cases, the disorder may
be discovered when abnormal serum enzyme levels are
identified during performance of routine screening tests.
