hepatitis b virus infection
DESCRIPTION
Hepatitis B Virus infection. Ermias D. (MD). History. Krugman et al (1967) – serum hepatitis/ HB Blumberg – Au Ag; (1976 Noble winner) Prince – SH Ag … HBsAg Opened up for rigorous investigations. Ethiopian epidemiology. - PowerPoint PPT PresentationTRANSCRIPT
Hepatitis B Virus infection
Ermias D. (MD)
History
Krugman et al (1967) – serum hepatitis/ HB
Blumberg – Au Ag; (1976 Noble winner) Prince – SH Ag
… HBsAgOpened up for rigorous investigations
Ethiopian epidemiology 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
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)
Core, viral genomeDNA 3.2kb
polymerase
8 subtypes group reactive and subtype Ag – a, d or y, w or r
Genes and proteins preS-S gene
S - Major (HBsAg), preS2 – middle (M), PreS1 - large (L) – binding, assembly, release
preC-C HBcAg – target of immune response HBeAg – marker of active replication
P region – viral polymerase – DNA synthesis, RNA encapsidation
X gene – gene expression, vivo replication, spread
Viral replication cycle 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 Viral replication – not cytotoxic
Many carriers - asymptomatic Host immune response – hepatocellular injury
Pt with immune defects – minimal injury In acute self limited disease – strong T cell response
– MHC II CD4 T, MHC I CD8 T 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 Virogous Ab response
Conti… 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 Primary infection is mostly asymptomatic Mostly self limiting with viral clearance and
lasting immunity 5% persistent infection – viral replication and
viremia continues Persistent infection:
Symptomatic (chronic) – abnormal liver function and histology
Asymptomatic (carriers) – normal serum amino transferase and histology
20% chronic – fibrosis and regenerative nodules (cirrhosis)
Viral DNA HBsAg HBeAg Anti HBc ALT AntiHBe AntiHBs
Viral DNA HBsAg Anti HBc HBeAg ALT
AntiHBe ALT
Hepatocellular carcinoma 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 Defective RNA virus
Requires host polymerase II for replication Require the helper function of HBV to cause liver injury
Endemic in HB infected Duration of infection cannot out last HBV infection
Transmission – close personal, percutaneous Simultaneous co infection
Chronic infection – <5%, fulminant failure 1%, mostly complete recovery
Super infection in HBsAg positives – fulminant failure 5% 80-90% chronic infection and rapid cirrhosis and HCC
Manifestation Similar to other viral hepatitis
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)
In HDV infection - 90% asymptomatic, similar sx HDV Ag 20%, HDV RNA 90% elevated transaminases
Extrahepatic manifestations
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 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
V/s in the normal ranges Wt 55kg
Pedal and pretibial gross pitting edema
Lab data
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
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
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
Protein lossing enteropathy Underlying cause ?? PUD
Long standing dyspepsia Polycythemia Elevated serum Cl- Low total protein and albumin