Download Acute And Chronic Viral Hepatitis Acute viral hepatitis

Acute And
Chronic Viral
Hepatitis
Acute
viral hepatitis is a systemic
infection affecting the liver predominantly.
Almost all cases of acute viral hepatitis
are caused by one of five viral agents:
◦ hepatitis A virus (HAV)
◦ hepatitis B virus (HBV)
◦ hepatitis C virus (HCV)
◦ hepatitis D virus (HDV)
◦ hepatitis E virus (HEV)
Acute hepatitis A
EPIDEMIOLOGY

HAV infection generally follows one of two
epidemiologic patterns:
 countries where sanitary conditions are poor,
most children are infected at an early age(100% of
preschool children)
 Industrialized countries, where the prevalence of
HAV infection is low among children and young
adults.
In the United States, the prevalence of anti-HAV
was approximately 10% in children but 37% in
adults.
Virology
 Hepatitis A
virus is heat-, acid-, and ether-resistant
RNA virus in the hepatovirus genus
 It
survives heat exposure of 60°C for 60 minutes but is
inactivated at 85°C for 1 minute.
 An
initial step in the life cycle of a virus is its
attachment to a cell surface receptor.
 Whatever
the entry mechanism, once HAV enters a
cell, the viral RNA is uncoated, cell host ribosomes
bind to viral RNA, and polysomes are formed.
transmission
transmission
of HAV is the fecal-oral
route or ingestion of contaminated
food or water.
Although
rare, transmission of HAV by a
parenteral route has been documented
after transfusion of blood or blood
products.
PATHOGENESIS
After
HAV is ingested and survives gastric acid
it
traverses the small intestinal mucosa and
reaches the liver via the portal vein.
Once
the virus enters the hepatocyte, it starts
replicating in the cytoplasm
When
the virus is mature, it reaches the
systemic circulation and into the biliary
tree, and eventually excreted in the feces.
CLINICAL FEATURES
 Infection
with HAV result in an acute self-limited
episode of hepatitis.
 The
incubation period is commonly 2 to 4 weeks,
 Children
younger than 2 years are usually asymptomatic;
jaundice develops in only 20% of them,
 whereas symptoms develop in most children (80%) 5
years or older.
 The
rate of symptoms is high in adolescents and
adults.
CLINICAL FEATURES

Prodromal symptoms (few days to 2 weeks) include
fatigue, weakness, anorexia, nausea, vomiting, and abdominal
pain and Dark urine . A low-grade fever between 38° and
39°C.
◦ Dark urine precedes other symptoms in approximately
90% of infected persons

Clinical jaundice:With the onset of clinical jaundice, the
constitutional prodromal symptoms usually diminish

Extrahepatic manifestations are less frequent in acute
HAV infection than in acute HBV infection and include:
◦ rash (14%)
◦ arthralgias (11 %)
◦ leukocytoclastic vasculitis, glomerulonephritis, and arthritis,
CLINICAL FEATURES
Right
upper quadrant tenderness(85%)
Mild liver enlargement (85%)
Splenomegaly (15%)
cervical lymphadenopathy(15%)
Laboratory Features
 The
serum AST and ALT show a variable
increase during the prodromal phase of
acute viral hepatitis and precede the rise in
bilirubin level
 The
acute level of these enzymes, however, does
not correlate well with the degree of liver cell
damage.
 Peak
levels vary from 400–4000 IU or more;
Laboratory Features
 Total
bilirubin rises to levels ranging from 5–20
mg/dL(equally divided between the conjugated and
unconjugated fractions)
 Neutropenia
and lymphopenia are transient and
are followed by a relative lymphocytosis.
 Prolongation
of the prothrombin time (PT) may
reflect a severe hepatic synthetic defect, signify
extensive hepatocellular necrosis, and indicate a
worse prognosis.
 Serum
alkaline phosphatase may be normal or only
mildly elevated,
Diagnosis
A
diagnosis of acute hepatitis A requires
demonstration of IgM anti-HAV in
serum.
 The
test result is positive from the onset of
symptoms and usually remains positive for
approximately 4 months
 IgG
anti- HAV is also detectable at the
onset of the disease, remains present
usually for life
Treatment
No
specific medications are available to
treat acute hepatitis A
symptomatic treatment is
the rule.

Prevention
Attention to sanitation
2. Administration of serum immune globulin
(IG)(0.02 mL/kg is recommended as early
after exposure as possible) up to 2 weeks
3. high-risk populations were targeted for
immunization
 universal childhood vaccination policy was
adopted in 2006, with the hope of eventually
eliminating indigenous HAV transmission in
the United States.
1.
postexposure prophylaxis
 For
postexposure prophylaxis of intimate contacts
(household, sexual, institutional) of persons with hepatitis A,
the administration of IG 0.02 mL/kg is recommended as
early after exposure as possible;
 it may be effective even when administered as late as 2 weeks
after exposure.
 Prophylaxis is not necessary for those:
 who have already received hepatitis A vaccine,
 casual contacts (office, factory, school, or hospital),
 for most elderly persons, who are very likely to be immune,
 or for those known to have anti-HAV in their serum
Prognosis
 Clinical
and biochemical recovery is to be
expected 1–2 months after all cases of
hepatitis A
 FULMINANT
HEPATITIS A(FHF) due to
HAV is rarely seen in children, adolescents,
or young adults.
 The
case-fatality rate of 0.3% in persons
of all ages
Acute Hepatitis B
Virology
Hepatitis
B virus is a DNA virus with a
remarkably compact genomic structure.
Hepatitis B isolates fall into one of at least
eight subtypes and eight genotypes (A–H).
Viral
Proteins and Particles
Hepatitis B Virus
HBV Genom
The
protein product of the S gene is HBsAg
(major protein),
HBV Genom
The
antigen expressed on the surface of the
nucleocapsid core is referred to as hepatitis
B core antigen (HBcAg), and its
corresponding antibody is anti-HBc.
hepatitis
B e antigen (HBeAg), a soluble,
nonparticulate, nucleocapsid protein that is
immunologically distinct from intact HBcAg
HBV Genom
Epidemiology
>350 million HBsAg carriers in the world.
groups with high rates of HBV

include
infection
spouses of acutely infected persons,
sexually promiscuous persons
health care workers exposed to blood
persons who require repeated transfusions especially with
pooled blood product concentrates (e.g., hemophiliacs)
 prisoners
 family members of chronically infected patients.
 persons with Down's syndrome, lepromatous leprosy,
leukemia, Hodgkin's disease, polyarteritis nodosa; in
patients with chronic renal disease on hemodialysis; and in
injection drug users.




Epidemiology

Percutaneous inoculation has long been
recognized as a major route of hepatitis B
transmission,
 in
approximately two-thirds of patients with
acute type B hepatitis, no history of an
identifiable percutaneous exposure can be elicited.
 HBsAg
has been identified in almost every body
fluid from infected persons, and at least some of
these body fluids—most notably semen and
saliva—are infectious, albeit less so than serum,
Epidemiology
Oral
ingestion has been documented as a
potential but inefficient route of
exposure.
By
contrast, the two nonpercutaneous
routes considered to have the greatest
impact are intimate (especially sexual)
contact and perinatal transmission.
Perinatal transmission
 occurs
primarily in infants born to HBsAg carrier
mothers
 10% of infections may be acquired in utero,
 most infections occur approximately at the
time of
delivery and are not related to breast feeding.
 The
likelihood of perinatal transmission of HBV:
90% of HBeAg-positive mothers
10–15% of anti-HBe-positive mothers
 In
most cases, acute infection in the neonate is
clinically asymptomatic, but the child is very likely to
become an HBsAg carrier
Clinical and Laboratory Features
 incubation
period for hepatitis B and D
from 30–180 days (mean, 8–12 weeks)
 Prodromal symptoms
 icteric phase symptoms
 hepatitis B is heralded by a serum sickness–like
syndrome.
 Complete clinical and biochemical recovery is to
be expected 3–4 months after the onset of
jaundice in three-quarters of uncomplicated, selflimited cases of hepatitis B
 among healthy adults, acute hepatitis B is
self-limited in 95–99%
Diagnosis
 diagnosis
of HBV infection can usually be
made by detection of HBsAg in serum.
 Infrequently, levels
of HBsAg are too low to
be detected during acute HBV infection, In
such cases, the diagnosis can be established
by the presence of IgM anti-HBc.
 The
titer of HBsAg bears little relation
to the severity of clinical disease
Treatment
In
hepatitis B, among previously
healthy adults who present with
clinically apparent acute hepatitis,
recovery occurs in ~99%;
therefore, antiviral therapy is
not likely to improve the rate
of recovery and is not required
Prevention(postexposure prophylaxis )
 For
perinatal exposure of infants born to HBsAg-positive
mothers, a single dose of HBIG, 0.5 mL, should be
administered IM in the thigh immediately after birth,
followed by a complete course of three injections of
recombinant hepatitis B vaccine to be started within the
first 12 h of life.

For those experiencing a direct percutaneous
inoculation or transmucosal exposure to HBsAg-positive
blood or body fluids (e.g., accidental needle stick, other
mucosal penetration, or ingestion), a single IM dose of
HBIG, 0.06 mL/kg, administered as soon after exposure
as possible, is followed by a complete course of hepatitis B
vaccine to begin within the first week.
Prevention(postexposure prophylaxis )
For
those exposed by sexual contact to
a patient with acute hepatitis B, a single
IM dose of HBIG, 0.06 mL/kg, should
be given within 14 days of exposure, to
be followed by a complete course of
hepatitis B vaccine.
When
both HBIG and hepatitis B vaccine
are recommended, they may be given at
the same time but at separate sites.
Clinical manifestations

The spectrum of clinical manifestations of hepatitis B virus
(HBV) infection varies in both acute and chronic disease.

During the acute phase, manifestations range from subclinical or
anicteric hepatitis to icteric hepatitis and, in some cases, fulminant
hepatitis

During the chronic phase, manifestations range from an
asymptomatic carrier state to chronic hepatitis, cirrhosis, and
hepatocellular carcinoma.

Extrahepatic manifestations also can occur with both acute
and chronic infection.
Chronic HBV
Chronic HBV(natural course)

The natural course of chronic hepatitis B virus
infection is determined by the interplay between
virus replication and the host immune response.

Chronic HBV infection generally consists of two
phases:
◦ an early replicative phase with active liver disease
◦ a late or low replicative phase with remission of liver
disease

In patients with perinatally acquired HBV infection,
there is an additional immune tolerance phase in
which virus replication is not accompanied by active
liver disease
Replicative phase(Immune tolerance)

In patients with a perinatally acquired HBV
infection, the initial phase is characterized by
high levels of HBV replication

the presence of HBeAg and high levels of HBV
DNA in serum—but no evidence of active
liver disease as manifested by lack of
symptoms, normal serum ALT
concentrations, and minimal changes on
liver biopsy .
Replicative phase(Immune tolerance)

The lack of liver disease despite high levels of
HBV replication is believed to be due to
immune tolerance to HBV

Experiments in mice suggest that the
transplacental transfer of maternal
HBeAg may induce specific
unresponsiveness of T cells to HBeAg and
to HBcAg, resulting in an ineffective cytotoxic
T cell lysis of infected hepatocytes
Replicative phase(Immune tolerance)

The immune tolerance phase usually lasts
10 to 30 years, during which there is a
very low rate of spontaneous HBeAg
clearance

The low rate of viral clearance in
adolescence and early adulthood accounts
for the high frequency of maternal-infant
transmission in Asian countries.
Replicative phase(Immune clearance)

The transition from the immune tolerant
to the immune clearance phase occurs
during the second and third decades
in patients with perinatally acquired HBV
infection.

During the immune clearance phase,
spontaneous HBeAg clearance
increases to an annual rate of 10 to
20 percent
Replicative phase(Immune clearance)

HBeAg seroconversion is frequently, but not
always, accompanied by biochemical
exacerbations (abrupt increases in serum ALT)
Exacerbations are believed to be due to a
sudden increase in immune-mediated lysis
of infected hepatocytes.
 They are often preceded by an increase in serum
HBV DNA and a shift of HBcAg (hepatitis B
core antigen) from nuclear to cytoplasmic
sites within hepatocytes
 How these changes occur is not known.

Replicative phase(Immune clearance)

Most exacerbations are asymptomatic and are discovered
during routine follow-up.

However, some are accompanied by symptoms of acute
hepatitis and may lead to the incorrect diagnosis of acute hepatitis
B in patients who are not previously known to have chronic HBV
infection
Exacerbations may be associated with an elevation in the IgM
anti-HBc titer, which may lead to misdiagnosis of acute HBV
infection and an increase in the serum alpha-fetoprotein
concentration
 exacerbations are more commonly observed in men than in
women . The reason for the gender difference is not clear, but a
higher frequency of exacerbations in men may at least in part
account for a higher incidence of HBV-related cirrhosis and
HCC among men.

Replicative phase(Immune clearance)

In a small percentage of patients,
exacerbations result in hepatic
decompensation and rarely death
from hepatic failure.
Replicative phase(Immune clearance)

Not all exacerbations lead to HBeAg
seroconversion and clearance of HBV DNA from
the serum, a phenomenon termed
abortive immune clearance

These patients may develop recurrent
exacerbations with an intermittent disappearance
of serum HBV DNA with or without a transient
loss of HBeAg

Such repeated episodes of hepatitis may
increase the risk of developing cirrhosis and
hepatocellular carcinoma (HCC).
Low or nonreplication phase
(inactive carrier state)

Patients in the low or nonreplicating
phase/inactive carrier state are HBeAg
negative and anti-HBe positive.

In some patients, HBV DNA is
undetectable in serum, even when tested
by polymerase chain reaction assays, and
liver disease is in remission as evidenced
by normal serum ALT concentrations and
the resolution of necroinflammation in liver
biopsies.
Low or nonreplication phase
(inactive carrier state)

Data indicate that significant liver disease
can be found in patients with HBeAgnegative chronic HBV who have a
persistently normal serum ALT.
Resolution of chronic HBV infection
Some patients with chronic HBV infection become HBsAg
negative.
 The annual rate of delayed clearance of HBsAg has been
estimated to be 0.5 to 2 percent in Western patients and much
lower (0.1 to 0.8 percent) in Asian countries


Clearance was preceded by a decrease in HBV DNA.

HBsAg clearance may be preceded by decreasing levels of HBsAg .

In most reports, patients without cirrhosis who cleared HBsAg
appeared to have a good prognosis. Despite a generally favorable
prognosis, clearance of HBsAg does not preclude the
development of cirrhosis or HCC.
Reactivation following seroconversion

A subset of patients who achieve HBeAg
seroconversion experience reactivation.
Reactivation can occur in patients who
receive immunosuppressive therapy,
but can also occur spontaneously
‫مهم‬
WHO SHOULD BE TREATED AND HOW
Patients in whom therapy is indicated:
acute liver failure,
 clinical complications of cirrhosis,
 cirrhosis or advanced fibrosis with high serum
HBV DNA,
 prevention of reactivation of chronic HBV
during chemotherapy or immunosuppression.
