Medical Microbiology: Hepatotrophic Viruses - May 3, 2017
Medical Microbiology: Hepatotrophic Viruses - May 3, 2017
Medical Microbiology: Hepatotrophic Viruses - May 3, 2017
HEPATITIS A
Viral shedding is approx. 10 days before the symptoms Period
Infectious Hepatitis of communicability
Formerly Enterovirus 72 in the Picornavirus family Liver pathology is indistinguishable histology from HBV
A picornavirus, the prototype of genus Hepatovirus Does not cause chronic liver disease
New genus: Heparnavirus Not associated with hepatic CA
Spread by fecal-oral route
Incubation period:15-50 days EPIDEMIOLOGY
Period of communicability: before to after symptoms appear Agent of acute hepatitis – approx. 40% of cases
Does not progress to chronic infection Period of communicability: 10-14 days before symptoms appear
Self-limiting infection
TRANSMISSION
Old age patient Susceptible to “Massive hepatic necrosis”
Virus can be transmitted via fecal-oral route
STRUCTURE Ingestion of contaminated food and water
Shellfish - important sources of the virus
Virus can be transmitted by food handlers, day-care workers,
and children
CLINICAL SYNDROME
REPLICATION
Replicates in the cytoplasm
Interacts with HAVCR-1 expressed on liver and T cells
o Specificity of HAVCR-1 correlates to the severity of the
disease cause by HAV
Flu-like symptoms or Jaundice
HAV is not cytolytic and released by exocytosis
Elevation of transaminases (ALT) Liver damage application to
o Massive necrosis related to HAV infection is not due
immune response against viral infected hepatocytes
to HAV itself but due to Immune Mediated Response
Dark urine Bilirubinuria
of the host against to hepatocytes infected with HAV
Symptoms are very similar to HBV
Symptoms occur 15-50 days after exposure
Symptoms wane during jaundice period
PROTOCAMBIUM, MD Page 1 of 7
MEDICAL MICROBIOLOGY
HEPATOTROPHIC VIRUSES – MAY 3, 2017
ARNEL G. BAYOTAS, M.D.
o Active immunization with killed HAV for two doses THREE MORPHOLOGIC FORMS OF HBsAg (Using Electron microscopy)
(initial dose + booster 6-12 months later)
Active immunization recommended for:
o Travelers to developing countries
o Children 2 – 18 years’ old
o Men who have sex with men
LABORATORY DIAGNOSIS
Basis for diagnosis:
o Time course of the clinical symptoms
o Identification of a known infected source
Serologic tests
o Anti-HAV IgM – ELISA or RIA
o Viral isolation is not performed
A. Small, spherical particles – most numerous; made up exclusively
HEPATITIS B of HBsAg
B. Tubular or filamentous forms – result from overproduction of
HBV is the major member of the hepadnaviruses HBsAg
Establishes chronic infections → liver disease and HCC C. Large, spherical virions – originally referred to as Dane particles
Infects the liver, lesser extent, the kidneys and pancreas
Only Hepatic viruses that has DNA genetic material
Partially double stranded DNA The positive strand is partially STRUCTURE
complete strand and negative strand is totally complete
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MEDICAL MICROBIOLOGY
HEPATOTROPHIC VIRUSES – MAY 3, 2017
ARNEL G. BAYOTAS, M.D.
REPLICATION
PATHOGENESIS
Major source of infection: blood
Other sources: semen, saliva, milk, vaginal & menstrual
secretions, and amniotic fluid
Most efficient way to acquire virus: injection of virus into the
blood stream
Common but less efficient routes: sexual contact and birth
Mother-to-child infection:
o Can be transmitted from a chronically-infected
mother to her child during the birthing process
o One of the most common modes of transmission for
Asians
Blood-borne infection:
o Wound-to-wound contact
o Blood transfusion
o Reusing syringes or medical services
o Sharing razors or toothbrushes contaminated by
blood
o Reusing or sharing needles for tattoos, piercings,
acupuncture, or injection drugs
HBV is NOT spread through:
o Sharing of food or water
o Sharing eating utensils or drinking glasses
o Tears, sweat, urine, or stool
o Coughing or sneezing
o Hugging or kissing ALT (transaminase)- signifies on-going liver damage
o Breastfeeding HBsAg- First marker, infected with HBV; denied for blood
o Mosquitoes donation. Appear before the onset of the symptoms; During the
disease, detectable 2-6 weeks in advance in clinical or
biochemical evidence of HBV
HBeAg- it is not the envelope, signifies active viral replication;
Highly infectious Viral Load increase
HBV DNA- found in the serum infected with HBV
Anti HBs- signifies immunity, recovery and vaccination;
sometimes it remains negative 4 to 6 months there is
possibilities that Anti HBs will gone
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MEDICAL MICROBIOLOGY
HEPATOTROPHIC VIRUSES – MAY 3, 2017
ARNEL G. BAYOTAS, M.D.
IgM-anti HBc- marker requested during recent infection/ acute What are the tests which you have to take?
infection/ window period, onset of the symptoms • ALT blood test – to determine whether treatment against HBV is
Anti HBe- occurs after several weeks after the appearance of IgM needed; monitor HBV disease progression
anti-HBc; appears after decrease of HBeAg. Decrease Anti HBe • HBV DNA level – direct measure of HBV viral load; helps evaluate
means viral replication is ceased treatment response
Over a period of months, IgM anti HBc is replaced by IgG anti • HBeAg and anti-HBe tests
HBc o HBeAg seroconversion (loss of HBeAg) and
Persistent elevation HBsAg and HBeAg is considered a chronic development of anti-HBe is a sign that the treatment
state of HBV is working
Differentiate between acute and chronic IgM anti HBc (4-6
months) Serologic Markers of HBV Exposure
IgG anti HBc usually occur during recovery or chronic stage of HBV core antigen (HBcAg)
infection or persis for life o Not detected in serum
Anti HBs develop immunity from disease, vaccination only o CTL epitopes expressed on hepatocyte surface in
Anti HBs + IgG anti HBc- natural infection, previous infection association with HLA-A2 molecules
Anti-HBc
Inactive HBsAg carrier state o Presence of high titers of anti-HBc IgM indicates early
• HBsAg (+) > 6 months acute infection
• HBeAg (-), anti-HBe (+) o Anti-HBc IgG can be detected in both acute & chronic
• Serum HBV DNA < 2,000 IU/ml HBV infection (remains for lifetime)
• Persistently normal ALT/AST levels HBeAg
• Liver biopsy confirms absence of significant hepatitis o “Early” appearance during acute infection
o Marker of high degree of infectivity
Chronic Hepatitis B o Correlates with high level of HBV replication
• HBsAg (+) > 6 months Anti-HBe
• Serum HBV DNA > 20,000 IU/ml (Lower values 2,000 – 20,000 o
IU/ml often seen in HBeAg (-) chronic hepatitis B end of replicative phase of disease
• Persistent or intermittent elevation in AST/ALT levels HBsAg
• Liver biopsy showing chronic hepatitis with moderate or severe o Marker of infectivity
necroinflammation o Presence in serum for at least 6 mos. Indicates chronic
infection
Resolved Hepatitis B Anti-HBs
• Previous known history of acute or chronic hepatitis B or the o Indicates an immune response to HBV infection or
presence of anti-HBc + anti-HBs vaccination, or the presence of passively acquired
• HBsAg (-) antibody (HBIG)
• Undetectable serum level of HBV DNA
• Normal ALT levels
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MEDICAL MICROBIOLOGY
HEPATOTROPHIC VIRUSES – MAY 3, 2017
ARNEL G. BAYOTAS, M.D.
QUICK TEST RESULT
RESULT INTERPRETATION
HBsAg (+) Chronic HBV infection if HBsAg remains (+)
Anti-HBs (-) for six months
HBsAg (-) Immune to HBV
Anti-HBs (+)
HBsAg (-) Unprotected; need vaccination
Anti-HBs (-)
HBsAg (+) Chronic HBV infection
Anti-HBs (+)
(rare)
Serologic Tests of Patient’s Diagnostic Interpretation TEMPORAL CHANGES IN SEROLOGIC MARKERS IN HEPATITS C VIRAL
Serum INFECTION
HBsAg IgM IgM
Anti- anti-
HAV HBc
+ - + Acute hepatitis B
+ - - Chronic hepatitis B
+ + - Acute Hepatitis A superimposed on chronic
HBV
+ + + Acute hepatitis A and B
- + - Acute hepatitis A
- + + Acute hepatitis A and hepatitis B (HBsAg
below detection level)
- - + Acute hepatitis B (HBsAg below detection
level)
- - - Test for acute hepatitis C (anti-HCV)
HEPATITIS C
PATHOGENESIS
Binds to cells using CD81 surface receptors OR coats itself with
LDL or VLDL uptake into hepatocytes remain in the ER and
is cell-associated
Bind to:
o TNFR inhibit apoptosis LABORATORY DIAGNOSIS
o Protein kinase R (PKR) inhibit interferon α Diagnosis and detection of HCV infection are based on ELISA
recognition of antibody.
CLINICAL SYNDROME o Seroconversion occurs within 7 to 31 weeks of
Acute disease similar to HAV and HBV infection but with less infection
intense inflammatory response and milder symptoms Recombinant interferon- α alone or with ribavirin is the only
Chronic and persistent hepatitis is the hallmark of infection known treatment
TRANSMISSION HEPATITIS D
Primarily in infected blood and sexually
Others: semen, vaginal secretions, transfusion, needle stick Responsible for causing 40% of the fulminant hepatitis infections
injury, shared drug paraphernalia, and breast-feeding Unique feature: uses HBV and target cell proteins to replicate
Almost all (>90%) HIV-infected individuals who are or were IV and produce its one protein → HBsAg essential for packaging the
drug users are infected with HCV virus
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MEDICAL MICROBIOLOGY
HEPATOTROPHIC VIRUSES – MAY 3, 2017
ARNEL G. BAYOTAS, M.D.
STRUCTURE INTERPRETATION OF HDV SEROLOGIC MARKERS
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MEDICAL MICROBIOLOGY
HEPATOTROPHIC VIRUSES – MAY 3, 2017
ARNEL G. BAYOTAS, M.D.
Chronicity/ NO YES YES YES NO
Carrier state
Other dse Fulminant PHC, PHC, Cirrhosis, NONE
assn’s rare cirrhosis, cirrhosis fulminant
fulminant
Lab diagnosis Symptoms Symptoms Symptoms and Anti-HDV ELISA ---
+ anti- & serum levels anti- HCV ELISA
HAV IgM of HBsAg,
HBeAg, and
anti- HBc IgM
ajc2017ENDajc2017
Protocambium, MD would like to thank these people for their generous contributions and
support
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