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home - Liver - Hepatitis B - Hepatitis B Pathogenesis Written by Dr Sebastian Zeki
Knowledge


Understands the serological interpretation categorisation and
investigation of patients with chronic hepatitis B and/or C with
particular emphasis on the need for treatment and surveillance

Recognises the particular populations at risk
Aware of national and international agreed guidelines on viral
hepatitis management and use of interferon and antiviral drugs

Aware of hepatitis B reactivation in the context of immunosuppression
Skills
Uses appropriate diagnostic modalities including serology
genotyping viral load measurements liver biopsy and related
investigations

Monitors anti-viral and immunomodulatory therapies with appropriate
investigations

Behaviours
Communicates effectively with patients and relatives in the context of
viral liver disease and underlying social and psychological risk factors

Marshals multi-disciplinary support networks and in particular
recognise the crucial role of nurse practitioners in disease
management

Also...

Knowledge


Identifies patients with acute hepatitis B and can a rtain the
severity of their illness

Defines the different phases of chronic hepatitis B infection with a
clear understanding of serological results

Appreciates risks of transmission to close contacts
Has awareness of indications for therapy in both HBeAg positive and
negative hepatitis and the potential influence of genotype on choice of
therapy

Identifies patients where prophylaxis is required to prevent
reactivation and vertical transmission

Can determine an appropriate surveillance programme for those
patients with varices and/or hepatocellular carcinoma

Identifies patients who are appropriate candidates for liver transplant


Skills
Demonstrates ability to take a relevant history perform examination
and organise appropriate investigations

Able to advise risks of viral transmission
Interprets results of blood tests for hepatitis B antigen and antibody
Appreciates when liver biopsy is appropriate
Be able to select the most appropriate treatment and how to monitor
patient response

Able to select appropriate imaging techniques for evaluation of
abnormal results
Behaviours
Appreciates the cultural differences in the ethnic populations infected
and the influence this may have on screening


Provides advice and education to families and shows appreciation of
the potential difficulties that may arise

Understands the importance of cooperation with virologists and staff
in other clinical laboratories

Hepatitis B Pathogenesis

The HBV genome replicates by reverse transcription via an RNA intermediate, the pregenomic RNA. The pregenomic RNA, nucleocapsid, and polymerase proteins are encapsidated in the virus core particle inside which reverse transcription takes place.The pregenomic RNA is the only RNA transcript which is encapsidated.Encapsidation is regulated by the pregenome encapsidation sequence (e) which is located in the precore and proximal core region. HBeAg HBcAg X protein(not needed for viral replication Genotypes —Eight genotypes (A to H) - clinical significance of the genotypes undetermined A new minus strand HBV DNA is produced followed by the synthesis of a new plus strand HBV DNA. Nucleocapsids with the partially double stranded HBV DNA can reenter the hepatocyte nucleus to produce more ccc DNA or be secreted as complete virions after coating with envelope proteins. Inside the hepatocyte nucleus, synthesis of the plus strand HBV DNA is completed and the viral genome is converted into a covalently closed circular DNA (ccc DNA). Replication cycle:This begins with the attachment of the virion to the hepatocyte membrane. The exact mechanisms of virus attachment are not clear but are thought to be mediated through the pre-S1 region of the virion envelope.The virion is uncoated in the hepatocyte cytoplasm and the viral genome enters the hepatocyte nucleus. Characteristics of the Virus:Belongs to the family of hepadnaviruses.The complete virion or Dane particle is 42 nm in diameter.It contains an envelope composed of viral-encoded proteins and host-derived lipid components.A core particle made up of the nucleocapsid protein, the viral genome, and the polymerase protein.HBV also produces 22 nm subviral particles in the form of filaments and spheres that are composed of envelope proteins only.Subviral particles do not contain the HBV genome and are therefore noninfectious. Hepatitis B Pathogenesis HBsAg HBcAg DNA polymerase/ reverse transcriptase HBV DNA HBsAg particles 5’ 3’ - 5’ HBsAggene + - Polymer-ase gene 10. -sense partly copied to + sense 9. + sense RNA copied to - sense DNA 8. Core assessmblies around + sense RNA 7. Viral proteins are translated 6. RNA enters cytoplasm 4. Entry of DNA into nucleus 5. Transcription of DNA to genomic and messenger RNA 13. Virus with partly double strand leaves the cell 12. Virus buds through host cell membrane 11. Core associates with HBS anitgen in cell membrane 1. HBV fuses bind to host cell membrane 2. HBV fuses with membrane. Core enters cytoplasm 3. Double stranded genome is completed by enzymes contained within the core Written by Dr Sebastian Zeki

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