serology for viral hepatitis
TRANSCRIPT
Mohamed Sabry Ass. Lecturer of Internal Medicine
Tanta Faculty of Medicine
Serology for viral hepatitis (HAV, HBV & HCV)
Hepatitis A virus:
Anti-hepatitis A virus IgM:
Positive at the time of onset of symptoms.Usually accompany the first rise in the alanine aminotransferase (ALT) level.
This test is sensitive and specific.The results remain positive for 3-6 months after the primary infection and for as long as 12 months in 25% of patients.
Anti-hepatitis A virus IgG:
Anti-HAV immunoglobulin G (IgG) appears soon after IgM and generally persists for many years.
The presence of anti-HAV IgG in the absence of IgM indicates past infection or vaccination rather than acute infection. IgG provides protective immunity.
HBV: Structure
HBV: virus proteins & particles:
HBV: Genomic structure:
Basics:
Deoxyribose nucleic acid (DNA) is the genetic material in all cells.
It is a double helix structure made of nucleotides.
Each nucleotide consists of a deoxyribose sugar, a phosphate group, and one of four bases: adenine, thymine, guanine and cytosine.
Protein products of the four genes
S gene: HBsAg S region: Major proteinS+preS2: Middle proteinS+preS2+preS1:Large protein
P gene: DNA polymerase
Directs replication and repair of HBV DNA
C gene: HBcAg
HBeAg
Translation begins with the C region.Translation begins at the preC region
X gene: HBxAg It can transactivate transcription of cellular and viral genesIt may contribute to carcinogenesis.
HBV: virus proteins & particles:
Protein products of the four genes
S gene: HBsAg S region: Major proteinS+preS2: Middle proteinS+preS2+preS1:Large protein
P gene: DNA polymerase
Directs replication and repair of HBV DNA
C gene: HBcAg
HBeAg
Translation begins with the C region.Translation begins at the preC region
X gene: HBxAg It can transactivate transcription of cellular and viral genesIt may contribute to carcinogenesis.
Viral proteins & particles:
Serology for HBV:
Antigen AntibodiesHepatitis B Surface Antigen (HBsAg)
Antibody to Hepatitis B Surface Antigen (Anti HBs)
Hepatitis B Core Antigen (HBcAg)
Antibody to Hepatitis B Core Antigen (Anti HBc IgM & Anti HBc)
Hepatitis B ‘e’ Antigen (HBeAg)
Antibody to Hepatitis B ‘e’ Antigen (Anti HBe)
Hepatitis B surface antigen (HBsAg):
It is the envelop protein expressed on the outer surface of the virion and on the small spherical and tubular structures.
It plays a major role in cell membrane attachment to initiate the infection process by binding to the hepatocyte plasma membrane
C Seeger, et al. (2000): Mol Biol Rev.
HBV: virus proteins & particles:
HBV: Precore mutation:
Basics
Mutations are sudden changes in an organisms genetic material that result from alterations in DNA that can be induced or appear spontaneously.
HBV: Genomic structure:
HBV: Precore mutation:
HBsAg Anti-HBsAg
Anti-HBc HBeAg Anti-HBe Interpretation
+ - IgM + -
HBsAg Anti-HBsAg
Anti-HBc HBeAg Anti-HBe Interpretation
+ - IgM + - Acute HB, High infectivity
HBsAg Anti-HBsAg
Anti-HBc HBeAg Anti-HBe Interpretation
+ - IgM + - Acute HB, High infectivity
+ - IgG + -
HBsAg Anti-HBsAg
Anti-HBc HBeAg Anti-HBe Interpretation
+ - IgM + - Acute HB, High infectivity
+ - IgG + - Chronic HB, high infectivity
HBsAg Anti-HBsAg
Anti-HBc HBeAg Anti-HBe Interpretation
+ - IgM + - Acute HB, High infectivity
+ - IgG + - Chronic HB, high infectivity
+ - IgG - +
HBsAg Anti-HBsAg
Anti-HBc HBeAg Anti-HBe Interpretation
+ - IgM + - Acute HB, High infectivity
+ - IgG + - Chronic HB, high infectivity
+ - IgG - + Chronic HB, low infectivity
HBsAg Anti-HBsAg
Anti-HBc HBeAg Anti-HBe Interpretation
+ - IgM + - Acute HB, High infectivity
+ - IgG + - Chronic HB, high infectivity
+ - IgG - + HBeAg negative precore
mutant HB
HBsAg Anti-HBsAg
Anti-HBc HBeAg Anti-HBe Interpretation
+ - IgM + - Acute HB, High infectivity
+ - IgG + - Chronic HB, high infectivity
+ - IgG - + Chronic HB, low infectivity
HBeAg negative
precore mutant HB
+ + +
HBsAg Anti-HBsAg
Anti-HBc HBeAg Anti-HBe Interpretation
+ - IgM + - Acute HB, High infectivity
+ - IgG + - Chronic HB, high infectivity
+ - IgG - + Chronic HB, low infectivity
HBeAg negative
precore mutant HB
+ + +
HBsAg Anti-HBsAg
Anti-HBc HBeAg Anti-HBe Interpretation
+ - IgM + - Acute HB, High infectivity
+ - IgG + - Chronic HB, high infectivity
+ - IgG - + Chronic HB, low infectivity
HBeAg negative
precore mutant HB
+ + + + + HBsAg of one subtype and
heterotypic antiHBs
HBsAg Anti-HBs Anti-HBc
HBeAg Anti-HBe Interpretation
- - IgM + +
HBsAg Anti-HBs Anti-HBc
HBeAg Anti-HBe Interpretation
- - IgM + + Acute HB (window)
HBsAg Anti-HBs Anti-HBc
HBeAg Anti-HBe Interpretation
- - IgM + + Acute HB (window)
- - IgG - +
HBsAg Anti-HBs Anti-HBc
HBeAg Anti-HBe Interpretation
- - IgM + + Acute HB (window)
- - IgG - + HB in the remote past
HBsAg Anti-HBs Anti-HBc
HBeAg Anti-HBe Interpretation
- - IgM + + Acute HB (window)
- - IgG - + HB in the remote past
Low level HB carrier
- + IgG - +
HBsAg Anti-HBs Anti-HBc
HBeAg Anti-HBe Interpretation
- - IgM + + Acute HB (window)
- - IgG - + HB in the remote past
- + IgG - + Recovery from HB
HBsAg Anti-HBs Anti-HBc
HBeAg Anti-HBe Interpretation
- - IgM + + Acute HB (window)
- - IgG - + HB in the remote past
Low level HB carrier
- + IgG - + Recovery from HB
- + - - -
HBsAg Anti-HBs Anti-HBc
HBeAg Anti-HBe Interpretation
- - IgM + + Acute HB (window)
- - IgG - + HB in the remote past
Low level HB carrier
- + IgG - + Recovery from HB
- + - - - Immunization with HBsAg
False positive
HCV• HCV antibody:
• Generally used to diagnose hepatitis C infection.
• Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears.
HCV• HCV-RNA:
• Various techniques are available e.g. PCR. Cut-off: 1000 copies / ml
• May be used to diagnose HCV infection in the acute phase.
• However, its main use is in monitoring the response to antiviral therapy.
HCV RNA (PCR testing)
Not a predictor of disease severity: a high viral load does not mean the liver disease is more severe, and a low viral load does not mean the patient is ok and does not need therapy!
Helps predict response rate to treatment (lower means a higher chance of cure with therapy)
HCV:
Genotyping: genotype 1 and 4 have a worse prognosis overall and respond poorly to interferon therapy.