Page 622 - Textbook of Pathology, 6th Edition

606 products, intravenous drug addicts, patients treated by renal
dialysis and hospital workers exposed to blood, and by
intimate physical contact such as from mother to child and
by sexual contact. The disease may occur at any age. HBV
infection causes more severe form of illness that includes:
acute hepatitis B, chronic hepatitis, progression to cirrhosis,
fulminant hepatitis and an asymptomatic carrier stage. HBV
plays some role in the development of hepatocellular
carcinoma as discussed later (page 634).

HEPATITIS B VIRUS (HBV). The etiologic agent for
hepatitis B, HBV, is a DNA virus which has been extensively
studied. Electron microscopic studies on serum of patients
infected with HBV show 3 forms of viral particles of 2 sizes:
Figure 21.6 Sequence of appearance of antibodies to HAV. small (spheres and tubules/filaments) and large (spheres)
as under:
Hepatitis A i) Small particles are most numerous and exist in two forms—
as 22 nm spheres, and as tubules 22 nm in diameter and
Infection with HAV causes hepatitis A (infectious hepatitis). 100 nm long. These are antigenically identical to envelope
Hepatitis A is responsible for 20-25% of clinical hepatitis in protein of HBV and represent excess of viral envelope protein
the developing countries of the world but the incidence is referred as hepatitis B surface antigen (HBsAg).
much lower in the developed countries. Hepatitis A is
usually a benign, self-limiting disease and has an incubation ii) Large particles, 42 nm in diameter, are double-shelled
period of 15-45 days. The disease occurs in epidemic form spherical particles, also called as Dane particles. These are
as well as sporadically. It is usually spread by faeco-oral about 100 to 1000 times less in number in serum compared
route. Parenteral transmission is extremely rare. The spread to small 22 nm particles and represent intact virion of HBV.
is related to close personal contact such as in overcrowding, The genomic structure of HBV is quite compact and
poor hygiene and poor sanitation. Most frequently affected complex. The HBV DNA consists of 4 overlapping genes
age is 5-14 years; adults are often infected by spread from which encode for multiple proteins (Fig 21.7):
children. 1. S gene codes for the surface envelope protein, hepatitis B
SECTION III
surface antigen (HBsAg); this protein product is termed major
HEPATITIS A VIRUS (HAV). The etiologic agent for protein. HBsAg is present on the outer surface of the large
hepatitis A, HAV, is a small, 27 nm diameter, icosahedral spherical particles as well as in small spherical and tubular
non-enveloped, single-stranded RNA virus. Viral genome structures. Pre-S1 and pre-S2 regions of genome are upstream
has been characterised but only a single serotype has been of S gene and code for pre-S gene protein products that
identified. HAV infection can be transmitted to primates and includes receptor on the HBV surface and for hepatocyte
the virus can be cultivated in vitro. Inactivation of viral membrane proteins. The protein product of S-gene plus
activity can be achieved by boiling for 1 minute, by ultraviolet
radiation, or by contact with formaldehyde and chlorine. The
virus is present in the liver cells, bile, stool and blood during
the incubation period and in pre-icteric phase but viral
Systemic Pathology
shedding diminishes after the onset of jaundice. Chronic
carriers have not been identified for HAV infection.

PATHOGENESIS. The mechanism by which HAV infection
causes hepatitis A is poorly understood. An immunologic
basis is suspected but the evidence in support is indirect in
the form of immunologic markers but not direct demons-
tration of the etiologic agent in the affected hepatocytes.
These markers are as follows (Fig. 21.6):
1. IgM anti-HAV antibody appears in the serum at the onset
of symptoms of acute hepatitis A.
2. IgG anti-HAV antibody is detected in the serum after acute
illness and remains detectable indefinitely. It gives life-long
protective immunity against reinfection with HAV.

Hepatitis B
Hepatitis B (serum hepatitis) caused by HBV infection has a
longer incubation period (30-180 days) and is transmitted
parenterally such as in recipients of blood and blood Figure 21.7 Genomic structure of hepatitis B virus (Dane particle).