Transcript Slide 1

Hepatitis B Virus infection
Ermias D. (MD)
History
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Krugman et al (1967) – serum hepatitis/ HB
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Blumberg – Au Ag; (1976 Noble winner)
Prince – SH Ag
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… HBsAg
Opened up for rigorous investigations
Ethiopian epidemiology
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E Tsega – serologic survey in 500 individuals from 5 regions
 6.2% HBsAg,
 42% overall viral markers,
 increasing pattern anti HBe and decreasing HBeAg with age
 3 individuals with delta Ab
Arsi region among 20-24 yrs – 80%
H. Kefenie – among AA hospital personnel's (432)
 HBsAg 9.02%
 antiHBs 46.25%
 antiHBc 73.6%
 at least one marker 76.38%
A. Abebe - seroepidemiology in AA
 HBsAg 7%
 HBeAg 23%
 increasing with age any marker 70% (40-49yrs)
Gondar 14.4% --- 8.2% (blood donors)
Review article (E. Tsega) - HBsAg 8-12%, over all markers 70 -79%
virology
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Hepadnaviridae – hepatotrophic DNA virus
Small amount in kidney, pancreas,
mononuclear cells
Infected cells produce two distinct subviral
lipoproteins – HBsAg (spheres and
filamentous forms)
Viral structure
40-42nm
Outer
lipoprotein
Envelope
(3 Surface Ag,
glycoprotein)
polymerase
Core, viral genome
DNA 3.2kb
8 subtypes group reactive and subtype Ag – a, d or y, w or r
Genes and proteins
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preS-S gene
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preC-C
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S - Major (HBsAg),
preS2 – middle (M),
PreS1 - large (L) – binding, assembly, release
HBcAg – target of immune response
HBeAg – marker of active replication
P region – viral polymerase – DNA synthesis, RNA
encapsidation
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X gene – gene expression, vivo replication,
spread
Viral replication cycle
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Fusion
Core presentation to cytosol – - then nucleus
DNA – cccDNA
RNA transcription (host RNA polymerase II)
Pass to cytoplasm
Translation of envelop, core, polymerase, x, preC
Assembly (including single RNA)
Sequential DNA synthesis (first from RNA by RT, the
second from the first synthesized DNA)
Recycle from the cytoplasm with in the cell itself or
bud out and infect other cells
pathogenesis
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Viral replication – not cytotoxic
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Host immune response – hepatocellular injury
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Pt with immune defects – minimal injury
In acute self limited disease – strong T cell response
– MHC II CD4 T, MHC I CD8 T
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Many carriers - asymptomatic
Cytotoxic T response against - core, polymerase, envelope
proteins (central roll in viral clearance)
Helper T against – C and P proteins
Chronic infection – attenuated T cell response
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Virogous Ab response
Conti…
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Transgenic mice - tolerant to HBV proteins and there
is no significant liver injury
Administration of cytotoxic T cell from syngeneic
animals – acute liver injury
Few hepatocytes are directly killed by the cyt. T cell
and their target
Secondary antigen nonspecific inflammatory
responses, cytotoxic by products of inflammatory
response, TNF, free radicals proteases, other immune
cells
TNF and IFN have antiviral effect with out killing target
cells – important for viral clearance
Cytokine release by un related hepatic infections has
similar effect
Natural history
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Primary infection is mostly asymptomatic
Mostly self limiting with viral clearance and
lasting immunity
5% persistent infection – viral replication and
viremia continues
Persistent infection:
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Symptomatic (chronic) – abnormal liver function
and histology
Asymptomatic (carriers) – normal serum amino
transferase and histology
20% chronic – fibrosis and regenerative nodules
(cirrhosis)
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Viral DNA
HBsAg
HBeAg
Anti HBc
ALT
AntiHBe
AntiHBs
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Viral DNA
HBsAg
Anti HBc
HBeAg
ALT
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AntiHBe
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ALT
Hepatocellular carcinoma
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100 times risk in chronically infected patients
HBsAg and HBeAg positive have higher risk
Even anti HBe antibody carriers have risk
Molecular mechanism incompletely
understood
Twice a year screening with serum α FP or
liver sonography or both
α-FP low positive predictive value (9-30)
Hepatitis D
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Defective RNA virus
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Endemic in HB infected
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Duration of infection cannot out last HBV infection
Transmission – close personal, percutaneous
Simultaneous co infection
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Requires host polymerase II for replication
Require the helper function of HBV to cause liver injury
Chronic infection – <5%,
fulminant failure 1%,
mostly complete recovery
Super infection in HBsAg positives –
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fulminant failure 5%
80-90% chronic infection and rapid cirrhosis and HCC
Manifestation
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Similar to other viral hepatitis
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IP 4-12 weeks
Prodromal symptoms – acute viral infection (1-2 wks)
Clinical Jaundice, nausea, vomiting, alteration in
olifaction and taste. Dark urine, clay like stool
Icterus, fever, RUQ tenderness
Recovery phase liver enlargement and functional
abnormality may persist (2-12 wks)
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In HDV infection - 90% asymptomatic, similar sx
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HDV Ag 20%, HDV RNA 90%
elevated transaminases
Extrahepatic manifestations
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Immune complex mediated
Serum sickness like syndrome (acute HB)
Glomerulonephritis (hypocomplementemic) with
nephritic syndrome
Polyarteritis nodosa
Essential mixed cryoglobulinemia (HCV)
Pulmonary hemorrhage, vasculitis
Acute pericarditis, polyserositis
Henoch-Schonlein purpura
Diagnosis
Case discussion
 38
yrs old male
 Bilateral leg swelling for 5 years
History
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Bilateral leg swelling since 4 wks following an acute episode of
diarrheal disease
The diarrhea was watery moderate in amount and subsided after four
days, pt took norfloxacillin
He has the leg swelling for the last five yrs waxing and wanning in
intensity
Gets worse with stressful situations, hot whether, and anorexia (poor
feeding)
Long standing dyspeptic sx – take anti acids, PPI, H2B
Infrequent use of paracitamol, diclofenac for migraine
Bowel habit is often constant with once per day, no stool color changes
2 pack yrs of smoking before 10 yrs
Nutritional hx - 3meals/day small;
No cardiac sx or illness before
No urinary abnormality
p/E
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V/s in the normal ranges
Wt 55kg
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Pedal and pretibial gross pitting edema
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Lab data
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14/11/01
Hgb 17.5
Total serum protien – 6 (LLN 6.2)
Alb - ??
Electrophoresis a/g 1.42 (normal)
UA, liver enzymes, renal function, FBS,
abdominal US --- normal
Dec. 2004
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Hgb – 17.1
ESR – 0
TFT – wnl
Doppler of the leg vessels – normal
ANA positive, LE body negative
Cl- 118
Abdominal US, UA, liver enzymes, RFT, Na,
K - wnl
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Wbc 8700 L% 11
Hgb – 19.3 MCV – 87
UA protein +, repeat – negative for protein
TSP 3.4, albumin 3.1
a/g – 1.31 (1.39 – 2.23)
ESR – 3
Cl- 117, CO2 13 (21-32)
Lipid profile, liver enzymes, PT, Na, K, RFT, - WNL
Stool 3X negative
H.pylori serology - Negative
discussion
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Protein lossing enteropathy
Underlying cause
?? PUD
Long standing dyspepsia
Polycythemia
Elevated serum ClLow total protein and albumin