HEPATITIS B
DEFINITION:
An infectious disease of the liver caused by the hepatitis B
virus (HBV) resulting in an acute or chronic hepatitis.
EPIDEMIOLOGY:
- incidence: 125/100,000; prevalence 2500-3000/year
- age of onset:
- peak between 30-39 years of age; rare in infancy/childhood
- risk factors:
- endemic (worldwide with 0.1-10% of the worlds' population
being HBV carriers; prevalence of carriers in various
populations may range from 5-80%; there are 300 million chronic
carriers)
- High Endemic Areas (7-20% chronic carriers): SE Asia, China,
Phillipines, Indonesia, Middle East, Africa, Amazon Basin,
Arctic - Canada has a low endemic rate: <5% anti-HBs positive
and <0.5% HBsAg positive (chronic carriers) but the prevalence
is in-creasing in North American due to an increased immigration
from high endemic regions
- transfusion recipients, IV drug users, tattooing and
acupuncture, institutionalized mentally retarded patients,
medical personnel and patients of renal dialysis units, ICU's,
and oncology units, dental, paradental, and parmedical personnel
PATHOGENESIS:
- a partially double-stranded circular DNA hepadnavirus 43
nm in diameter
- a double-shelled particle with an external coat composed
of Hepatitis B surface antigen (HBsAg) and an internal coat
composed of Hepatitis B core antigen (HBcAg)
- the core contains the HBV genome (which has been cloned
and sequenced), DNA-dependent DNA polymerase, and Hepatitis B
e antigen (HBeAg)
- HBV can be detected in saliva, semen, and in many other
body fluids with the major reservoir being chronic carriers -
modes of transmission:
- perinatal - carrier mother to child
- horizontal - oral-oral person to person
- sexual or intimate physical contact of any type
- parenteral/percutaneous (with transfusions of blood,
plasma, or other blood products) (33% of cases have an
unrecognized source)
2. Hepatitis B
- previously called "serum hepatitis"
2. Pathogenesis
- infection -> 50-180 days incubation period -> two responses:
- no clinical features of infection
2. Clinical Infection (20-25%)
- may be icteric or anicteric
- infection results in noncytopathogenic injury to
hepatocytes but hepatocellular necrosis due to the cellular
& immune response of the host to HBV infection - there are 3
outcomes:
- represents an effective immune response which results
in the complete elimination of the virus
2. Chronic Carrier
- represents an ineffective immune response which
results in an persistent HBV infection (? due to a lack of
alpha interferon)
3. Fulminant Hepatitis
CLINICAL FEATURES:
- arthritis and rash may be present
2. Hepatitis
- insidious onset with duration of illness ranging from
several weeks to months
- while the preicteric phase can last up to 5 days, the
icteric phase lasts from days to months with a mean of 8-11 days
in children
- may be absent in children but last up to 5 days in
adolescents
- ranges from 37.8-40 C
2. Accompanying Signs/Symptoms
- abdominal pain
- anorexia
- headache
- letheragy/fatigue
- nausea/vomiting
- hepatomegaly (tender)
- lymphadenopathy
- splenomegaly
2. Icteric Phase
- transition to the icteric phase is marked by the
disappearance of preicteric signs/symptoms in young children
but the exacerbation of these signs/symptoms in older
children and adolescents
3. Hepatic Complications
- persistence of HBsAg for >6 months
- risk of chronicity decreases with age:
- newborns (80-90%)
- children <5 years (25-50%)
- adults (6-10%)
- about 80% of chronic carriers remain asymptomatic with
5-15% per year remiting spontaneously (in those that clear,
HBeAg clears and anti-HBe subsequently rises)
- the other 20% develop temporary exacerbations of the
disease (elevated AST)
- chronic persistent and active HEPATITIS Bre considered old
terms which do not reflect on the clinical manifestations of
chronic hepatitis
- a pathological diagnosis based on finding an
inflam-atory process on liver biopsy involving only the
portal areas
- moderate elevation of AST
2. Chronic Active Hepatitis
- chronic and recurrent episodes of jaundice and
elevated
- ALT and AST
- may progress to cirrhosis +/- portal hypertension with
ascites
2. Liver Failure
- liver failure occurring within days to 4 weeks after the
onset of acute hepatitis
- associated with mental confusion, emotional instability,
restlessness, bleeding, and coma
- no way of predicting which patients will progress to
fulminant hepatitis
2. Subacute Hepatitis
- liver failure occurring 1-3 months after the onset of
acute hepatitis
3. Hepatocellular Carcinoma
- presents in the 3rd-4th decades in chronic carriers
- the HBV genome is found integrated into the tumor cell
genome
4. Extrahepatic Complications
- due to a diffuse widespread immune complex-type vasculitis
affecting the skin, joints, small arteries and arterioles, and
renal glomeruli
- occurs during the latter part of the incubation period
or early acute phase of the disease and persists for only a
few days
- due to the deposition of immune complexes in the skin
and joints
- clinical features:
- transient erythematous maculopapular eruption
- urticaria
- polyarthralgias, arthritis
2. Polyarteritis Nodosa
- associated with persistent HBV antigenemia
- due to the deposition of immune complexes, HBsAg, IgG,
IgM, and C3 in the elastic membrane of small vessels
resulting in fibrinoid necrosis and perivascular
infiltration
- initial features:
- fever
- rash, urticaria
- polyarthralgias, myalgias
- evolves into features of acute vasculitis:
- peripheral neuropathies
- hypertension with renal damage
3. Glomerulonephritis (GN)
- associated with chronic HBV infection
- deposition of immune complexes, HBsAg, IgG, and C3 in
the glomeruli results in a membranous or
membranoproliferative type of GN
INVESTIGATIONS:
- gradual rise in level after the incubation period over
several weeks and remains elevated for 30-60 days before
declining
2. Bilirubin
- transient elevation associated with the peak in ALT
levels lasting up to 2 months
3. Serology
- first antibody to be detected
- appears 1 week or more after the onset of signs/
symptoms and is initially predominantly IgM which is high
for several months before declining to low or undetectable
levels
- the presence of IgM Anti-HBc indicates recent or acute
HBV infection
- IgG Anti-HBc persists for many years
2. Anti-HBe
- appears next and begins to rise about 5-6 weeks after
the onset of signs/symptoms, peaks over 1-2 months and
then declines
- develops after HBeAg has cleared, i.e., the virus is
no longer replicating
3. Anti-HBs
- usually appears late and begins to rise 3 months after
the onset of signs/symptoms and when HBsAg is no longer
detected (after the "window")
4. Viremia
- detection is evidence of a HBV infection
- may be detected 6-30 days after parenteral ex-posure
and 56-60 days after an oral exposure - appears 1 wk to 2
months before the onset of signs/sypmtoms and then may
become undetectable shortly after the onset of jaundice
2. HBeAg
- detected at the same time as HBsAg but declines sooner
(after 6 weeks)
- indicates replicating virus
Note: Best indicators of an acute infection are HBsAg
and anti-HBc IgM
2. Chronic Hepatitis
- gradual rise in level after the incubation period over
several weeks and remains elevated for up to 5 years before
declining
2. Serology
- IgG Anti-HBc persists for years
2. Anti-HBe
- may begin to rise 5 years after exposure and persists
for years
- rise is associated with a decline in ALT levels
3. Viremia
2. HBeAg
- persists until the rise in anti-HBe
MANAGEMENT:
2. Alpha-Interferon
- effective in about 5% of patients
- used in chronic carriers in an attempt to clear the virus
- a recombinant drug given for 16 weeks costing up to $5000
- better responders (50% chance of clearing the virus)
- high pretreatement ALT - HIV negative
- low pretreatment HBV-DNA - Western origin
- active liver disease - females
- adulthood - heterosexuals
- short duration - anti-HDV negative
3. Prognosis
- can result in chronic hepatitis, liver disease, and/or a
carrier state (with a high risk of perinatal infection)
- mortality from fulminant hepatitis is:
- <2% in uncomplicated cases
- 2% in complicated cases
4. Perinatal HBV Infection
- most HBV-infected infants, born to mothers who are HBV
carriers, have a chronic asymptomatic infection and no evidence
of neo-natal jaundice
- all pregnant women should be routinely screened for HBsAg as
most infants infected in the perinatal period develop chronic
infection
- an infant of a HBsAg-positive mother should be given 0.5cc
of Hepatitis B Immune Globulin immediately following birth
followed by three doses of Hepatitis B Vaccine, the first dose
given within the first week of life and subsequent doses at one
and six months of age; this will prevent Hepatitis B infection
in the infant
5. Hepatitis B Vaccine
- use for prophylaxsis/prevention
- recombinants: Recombivax-HB, Engerix-B
- in the process of recommending universal immunization of
children (age 10) but no agreement on the optimal immunization
schedule - vaccination of high risk groups and in certain
situations
- costs about $150
- SE: fever, pain, allergic reaction, rash, anaphylaxis,
hypotonic-hyporesponsive episode, arthralgia, arthralgia, sever
vomiting or diarrhea
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