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.