Transcript Viral Hepatitis

Viral Hepatitis
Moa`th Alazizi, MD
Internal Medicine
Gastroenterologist & Hepatologist
2012
Types
There are 5 types of known viruses that
may lead to viral hepatitis.
 HAV, HBV, HDV, HCV and HEV.
 HAV and HEV infection may lead to acute
hepatitis only and not chronic hepatitis.
 HBV and HCV infection may induce acute
and chronic hepatitis.
 HDV infection have to be concomitant or
superimposed HBV hepatitis.
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Hepatitis A virus
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First reference to epidemic jaundice has been
described to Hippocrates.
It accounts for 20-25% of clinical hepatitis in the
developed world.
It is due to a small 27-nm cubically symmetrical
RNA Picorna virus.
The virus is absorbed from the gastrointestinal
tract and reaches the liver where it is engulfed.
Viral proteins are synthesized and packed into
vesicles to be released into bile.
The virus is not directly cytopathic and damage
is caused by T cell mediated immune responses.
 The serum antibody appears as the stool
becomes negative for virus
 IgG anti-HAV gives immunity from further
infection with hepatitis A.
 IgM anti-HAV demonstrate recent infection with
HAV and they persist only for 2-6 months and
rarely up to 1 year.
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Epidemiology
The disease occurs sporadically or in
epidemic form and has an incubation time
of 15-50 days.
 Spreading way is fecal-oral route.
 Most affected group is aged 5-14 years
and adults are usually infected by spread
from children
 Spread is related to overcrowding and to
poor hygiene and sanitation.
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Clinical course
In children the clinical course is usually mild and subclinical or pass off as gastroenteritis.
 The disease is more serious and prolonged in adults
where cholestatic forms are seen frequently, and
jaundice may last 42-110 days.
 Acute viral hepatitis may induce nephrotic syndrome due
to immune complex, mesangial, proliferative
glomerulionephritis.
 Also hepatitis A may trigger chronic autoimmune
hepatitis type 1 in genetically predisposed individulas
(due to defects in T cell suppressor-inducer cells).
 Fulminant hepatitis occurs in 1% of cases.
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Relapsing hepatitis A occurs occasionally after
30-90 days when transaminases does not return
to normal and it may persist several months,
and may be associated with arthritis, vasculitis
and cryoglobulinemia.
 Vaccination anti-hepatitis A is produced from
inactivated viral particles with formaldehyde.
 The vaccination scheme include 2 doses, initial
and 6-12 months booster.
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Indications for vaccination
Travelers.
 Occupational exposure (food handlers,
sewage workers, nurses, ICU
workers…etc)
 Epidemics .
 Mass immunization in children?
 Chronic liver disease (HCV)?
 Homosexual males.
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Hepatitis E virus
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This accounts for sporadic and major epidemics
of viral hepatitis in developing countries.
Disease is enterically transmitted (fecal-oral
route), usually by sewage-contaminated water.
The virus is a 32-34-nm RNA virus,
unenveloped.
It resembles calciviruses but has not be
classified yet, and has been placed in a new
group called herpesviridae.
It is direct cytopathic virus and cause minimal
immunological injury.
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It is secreted in the bile, but fecal excretion is
low, that is why there is low secondary spread.
Immunity is weak in this infection and longevity
of protective antibody is uncertain.
Clinical picture of this hepatitis resembles
hepatitis A, with incubation period of 22-46 days
for blood and 34-46 days for feces.
Onset is abrupt, jaundice in majority of the
cases, but there is no chronic course.
Acute fulminant hepatitis occurs in 1-2% and up
to 10-20% for pregnant women.
Diagnosis of HEV
HEV IgM can be detected by ELISA within 10-12
days of acute illness, and it disappears within 6
months.
 HEV IgG appears at 10-12 days also of acute
illness and remains positive for a long period of
time.
 Prevention by better sanitation and hygiene
education, clean water supply.
 Up to date there is no vaccine for this virus.
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The hepatitis E virus is endemic in
countries with poor sanitation, where it
has many similarities with the hepatitis A
virus. It causes a strictly human, feco-oral
transmitted, acute, self-limited hepatitis in
young adults. The outcome is excellent,
except in pregnant women and cirrhotic
patients, who experience a high mortality
rate.
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The first cases described in industrialized
countries were travellers coming from
endemic areas. However, there is now
growing evidence that locally-acquired
hepatitis E is common in these areas,
where it is an emergent disease, despite it
is still misdiagnosed.
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In industrialized countries, hepatitis E
spreads sporadically and has a predilection
for elderly men with comorbidity,
particularly chronic liver diseases.
Hepatitis B virus
First discovered in 1965 in Philadelphia by
Blumberg from an Australian Aborigine (named
at that time Australia Antigen), then it was
recognized as a viral hepatitis virus. In 1977
Blumberg was awarded with a noble prize for his
discovery.
 Australia antigen is now named surface antigen
known as HBsAg.
 Over 2 billion people alive today have been
infected with HBV and over 350 million of them
are chronically infected carriers who have no
significant liver disease.
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The worldwide prevalence of HBV infection is falling due
to vaccination and better hygiene regarding shared
syringes and needles and sterilization.
Contamination occurs vertically (from mother to child
during labor) or horizontally( shared needle drug abuser,
contaminated blood products transfusion, needle-stick
injury, sexual transmission, shared toothbrushes and
razors, dentist instrumentation and barber
instrumentation).
Kissing and blood-sucking arthropods such as
mosquitoes or bed bugs may have a role mainly in the
tropics (not will documented).
HBV is a small encapsulated DNA virus, the core
contain DNA, DNA polymerase, HBcAg and
HBeAg.
 The virus is covered by HBsAg.
 The virus is not directly cytopathic, it is
mediated by immune response and the lysis of
infected hepatocytes is done by the antibodies
directed against infected hepatocytes with HBV.
 The virus enters in the blood stream of the
infected person and reaches the portal
circulation up to the liver and infect the
hepatocytes.
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The virus integrate in the genome of the hepatocytes
and replicate within them and expose the HBsAg upon
the external membrane if the hepatocytes.
 The immune system of the infected person recognize the
infected cells and Ab against infected HBsAg and
infected hepatocytes are formed, and damage occurs.
 Viral persistence is related to specific failure of cytotoxic
T lymphocytes (CTL) to recognize HBV antigen.
 Normally self limited infection is mild to moderate and
termination of viral infection and resolution of the
infection occurs (90%)=acute hepatitis B.
 If the destruction of hepatocytes is high (exaggerated
immune response) fulminant hepatitis occurs.
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Acute hepatitis B
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Acquired by contact with blood or body fluids containing
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Infectivity only for blood, genital secretions and
HBV.
occasionally saliva.
 Incubation period ranges from 6-26 weeks (Average 12
weeks).
 HBS appear first in the incubation period, and disappears
within 3 months from the onset usually.
 HBV DNA and HBeAg appear also at the same period.
 Symptoms appear when the concentrations of bilirubin
and ALT are high and this coincide with the appearance
of HBV Ab (>4weeks).
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HBeAg IgM appear first, at the onset of the
symptoms (its an indicator of acute infection), it
persists for at least 6 months, IgG persists
lifelong.
 HBeAb appear as second Ab, it is associated
with the clearance of HBeAg. Later it declines
and persists only for few months or years, if
there is no viral replication.
 HBsAb appear after 3-6 months, after acute
infection (it is a marker of immunity to HBV).
Chronic hepatitis B
1-10%.
> 85-95% of newborns and children infected
under age of 3 years, born to HBeAg positive
mother, become chronic carriers. (Due to
immunological immaturity in the children).
 Persistence of HBsAg > than 6 months.
 If HBV DNA and HBeAg persist high, it is a
marker of chronic active infection.
 Long standing infection may enter low level of
replication (HBeAg cleared and produce HBeAb
and low level of HBV DNA) called carriers.
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Acute hepatitis, HBS Ag < 6 months
Chronic hepatitis, HBS Ag > 6 months.
Evolution of HBV infection: 5% of infected
have acute hepatitis (from that 1% have
fulminante hepatitis, and 99% heal).
65% have sub clinical infection, which heals
100%.
10% have chronic hepatitis B, which evolve in
cirrhosis in 10-30% and develop in HCC.
Rest of 70-90% is carrier of HBS Ag.
Individuals at increased risk of
acquiring HBV infection that should be
routinely vaccinated
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Newborns of carrier mothers.
Children under 10 years in high (>2%)
prevalence communities.
Household contacts of acute and chronic
hepatitis B carriers (excluding sexual partners).
People at risk of sexual transmission.
Injection drug users.
Haemodialysis patients(often poor vaccine
responders)
Blood concentrate recipients.
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Persons with chronic liver disease/hepatitis C.
Residents and staff of facilities for the
intellectually disabled.
Close contact of de-institutionalized people
with intellectual disabilities.
Long term prison inmates and staff of
correctional facilities.
Health cares workers.
Others: police, day care workers, armed
forces, travelers to endemic countries
Serological diagnosis
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HBsAg appears in the blood about 6 weeks after
infection, and in 90% it disappears at 3 months after the
illness, when HBsAb appears (lifelong immunity).
Persistence more than 6 months means development of
carrier state.
HBeAg correlates with ongoing viral synthesis (infectivity
and replication) appears at the same time with HBsAg, if
it persists more than 10 weeks its denotes chronicity.
Anti-HBe is a marker of low infectivity (it is a marker that
the patient will not recover completely).
HBcAg are not detected in the circulating blood, the antiHBc can be detected in blood
High titers of IgM anti-HBc mark acute hepatitis B.
IgG anti-HBc indicates chronicity or previous infection (if
associated with HBsAb).
Treatment
Acute hepatitis will not necessitate any
treatment.
 Acute fulminant hepatitis will necessitate
admission in ICU, with strict monitoring of vital
signs, P.T, …etc, with strong indication of liver
transplantation (90% mortality).
 Chronic hepatitis needs treatment ( Pegylated
interferon, lamuvidine, Adefovir, Entacavir …etc)
 Carrier state does not need treatment (low
infectivity and low replication), only close
monitoring of LFT and viral markers periodically.
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Prognosis
Acute hepatitis B resolve within 5-6
months in 90% (Sero-conversion of HBsAg
in HBsAb, HBeAg - , HBeAb +).
 9% will be chronic Healthy carries
(HBsAg+ ,HBsAb - , HBeAg - , and
HBeAb+). Also HBV DNA by PCR - .
 1% will have Chronic active hepatitis
(HBsAg +, HBsAb - , HBeAg +, HBeAb)
and HBV DNA by PCR is high.
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Prognosis II
Chronic hepatitis B will lead eventually to liver
cirrhosis ( firstly compensated then
decompensated) within 20 years of evolution.
 Hepatocellcarcinoma (HCC) is another
complication of chronic hepatitis B.
 So for chronic hepatitis B and liver cirrhosis
always monitor the decompensation signs
(ascites, encephalopathy, portal hypertension)
and HCC (by ultrasonography and alfafetoprotein).
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Hepatitis C virus
250 - 300 million infected worldwide.
 USA: 3-4 million.
 Americas: 12-15 million.
 Africa: 30-40 million.
 Fareast Asia: 60 million.
 Southeast Asia: 30-35 million
 Australia: 0,2 million.
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Hepatitis D ( HDV)
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Is an enveloped RNA virus. It is a subviral
satellite because it can propagate only in the presence
of (HBV).
Transmission of HDV can occur either via simultaneous
infection with HBV (coinfection) or superimposed on
chronic hepatitis B or hepatitis B carrier state
(superinfection).
& Both results in more severe complications compared to
infection with HBV alone eg; liver failure in acute
infections and a rapid progression to liver cirrhosis, with
an increased chance of developing liver cancer in chronic
infections.
 In combination with hepatitis B virus, hepatitis D has the
highest mortality rate of all the hepatitis infections of 20%.
HCV
HCV virus is an RNA virus (Flavivirus
family)
 HCV is related to HGV, yellow fever virus,
and dengue virus.
 Natural targets are 1. Hepatocytes and
possible
2. B lymphocytes
 Six genotypes and multiple subtypes
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Clinical course
Hepatitis C virus  acute hepatitis C (anti-HCV)
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 1. Resolved spontanously(20-30%) [HCV RNA negative, IgM anti-HCV negative, ALT
normal].
 2. HCV carrier (20-30%) [HCV-RNA positive,
IgM anti HCV negative, ALT normal] 
cirrhosis/HCC ?%
 3. Chronic hepatitis C (40-60%) [HCV-RNA
positive, IgM anti-HCV positive, ALT increased]
 Cirrhosis (20%)  HCC
Course of the disease
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74-86% are chronic (persistent viremia,
asymptomatic)
15-25% resolves the infection.
The interval between infection and the development of
cirrhosis can exceed 30 years.
Cirrhosis develop from chr.hep.C (15-20%)
Factors that accelerate clinical progression: Alcohol
intake, co-infection with HIV or HBV, male, older age
at infection.
Risk of HCC for the cirrhotic C patient is 1-4% / year.
HCC without cirrhosis can occur but more rare than
HBV infection
Clinical features
Clinical manifestation can occur within 7 to
8 weeks (2 to 26) after exposure to HCV.
 Majority do not have /or have mild
symptoms.
 Fulminant hepatitis very rare (not known).
 Symptoms if exists are jaundice, malaise
and nausea
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Routs of transmission
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Shared needles.
Hemodialysis.
Tattooing.
Needlestick and sharp injuries
Saliva (bites)
Perinatal: Maternal-fetal transmission occurs but is
infrequent
Sex: uncommon
Intrafamilial: uncommon.
Blood transfusion
Blood products
High-risk groups
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Intravenous drug abusers.
History of imprisonment: in prisons, with those with
high-risk behaviors for transmission of HIV and HBV.
Hemodialysis patients.
Healthcare workers exposed to needle-stick and sharp
injuries.
Recipients to blood transfusion prior to screening of
donors.
Current recipients of multiple blood transfusions.
Hemophiliacs given clotting factors prior to screening
and decontamination.
Therapeutic procedures: colonoscopy, dialysis, surgery
and anesthetic tube.
Treatment
Acute hepatitis C (if diagnosed), treatment with regular
Interferon (IFN) 5 MU e.o.d for 4 months or Pegylated
interferon alone (monotherapy) weekly for 4 months.
 Chronic hepatitis C treat with Pegylated interferon
weekly and Ribavirin (combination therapy).
 Chronic inactive carriers do not treat but close monitor.
 Compenstaed active cirrhosis treat with combination
therapy.
 Decompensated cirrhosis do not treat.
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1. Cryoglobulins: Cryoprecepitate that contain
large amounts of HCV Ag and Ab. Only 10-15
have symptomatic disease ( related to
vasculitis = weakness + Arthralgia + purpura)
2. Vasculitis.
3. Membrane proliferative glomerulonephritis.
4. Involvement of the nerves and brain.
5. Essential mixed cryoglobulinemia (type II
cryoglobulinemia)- 90% have HCV viremia.
6.Non-Hodgkin's lymphoma (with or without
cryoglobulinemia)
7.Lichen planus.
8.Sicca syndrome - Sjogren syndrome: HCV infection may
trigger a focal reaction resulting in lymphocytic
sialoadenitis that is histologic changes in the salivary
glands characteristic for Sjogren syndrome.
9.Porphyria cutanea tarda. (PCT): HCV may act as a
trigger to development of PCT in predisposed
individuals. All patients with PCT should be tested for
HCV, if founded with liver disease, they should be
treated with IFN.