Monday, September 29, 2008

Hepatitis viruses

  1. human hepatitis viruses are RNA viruses, except for hepatitis B, which is a DNA virus
  2. progressive chronic liver disease with cirrhosis and even hepatocellular carcinoma, common to the bloodborne types (HBV, HCV, and HDV)

    Hepatitis A

    1. ether-resistant RNA virus
    2. Inactivation of viral activity can be achieved by boiling for 1 min, by contact with formaldehyde and chlorine, or by ultraviolet irradiation
    3. one serotype.
    4. Hepatitis A has an incubation period of approximately 4 weeks.
    5. Its replication is limited to the liver, but the virus is present in the liver, bile, stools, and blood during the late incubation period and acute preicteric phase of illness
    6. viral shedding in feces, viremia, and infectivity diminish rapidly once jaundice becomes apparent
    7. Antibodies to HAV (anti-HAV) can be detected during acute illness when serum aminotransferase activity is elevated and fecal HAV shedding is still occurring
    8. early antibody response is predominantly of the IgM class
    9. During convalescence, however, anti-HAV of the IgG class becomes the predominant antibody
    10. diagnosis of hepatitis A is made during acute illness by demonstrating anti-HAV of the IgM class.
    11. After acute illness, anti-HAV of the IgG class remains detectable indefinitely, and patients with serum anti-HAV are immune to reinfection

    Hepatitis B

    1. a DNA virus
    2. HBV is now recognized as one of a family of animal viruses, hepadnaviruses (hepatotropic DNA viruses), and is classified as hepadnavirus type 1
    3. Instead of DNA replication directly from a DNA template, hepadnaviruses rely on reverse transcription
    4. HBV is difficult to cultivate in vitro in the conventional sense from clinical material
    5. Geographic distribution of genotypes and subtypes varies
    6. Clinical course and outcome are independent of subtype,
    7. hepatitis B surface antigen (HBsAg) hepatitis B core antigen (HBcAg), and its corresponding antibody is anti-HBc. A third HBV antigen is hepatitis B e antigen (HBeAg), a soluble, nonparticulate, nucleocapsid protein
    8. HBeAg, which has a signal peptide that binds it to the smooth endoplasmic reticulum and leads to its secretion into the circulation
    9. HBcAg is the protein product; it has no signal peptide, it is not secretedHBcAg particles remain in the hepatocyte, where they are readily detectable by immunohistochemical staining naked core particles do not circulate in the serum
    10. HBeAg, provides a convenient, readily detectable, qualitative marker of HBV replication and relative infectivity.
    11. HBsAg-positive with HBeAg is more highly infectious and associated with hepatitis B virions (and detectable HBV DNA, ) than HBeAg-negative or anti-HBe-positive serum. For example, HBsAg carrier mothers who are HBeAg-positive almost invariably (>90%) transmit hepatitis B infection to their offspring, whereas HBsAg carrier mothers with anti-HBe rarely (10 to 15%) infect their offspring
    12. during the course of acute hepatitis B, HBeAg appears transiently; its disappearance may be a harbinger of clinical improvement and resolution of infection
    13. Persistence of HBeAg in serum beyond the first 3 months of acute infection may be predictive of the development of chronic infection,
    14. the presence of HBeAg during chronic hepatitis B is associated with ongoing viral replication, infectivity, and inflammatory liver injury.
    15. DNA polymerase has both DNA-dependent DNA polymerase and RNA-dependent reverse transcriptase activities
    16. hepatitis B x antigen (HBxAg), that is capable of transactivating the transcription of both viral and cellular genes
    17. clinical association observed between the expression of HBxAg and antibodies to it in patients with severe chronic hepatitis and hepatocellular carcinoma


First virologic marker detectable in serum is HBsAg

  1. Circulating HBsAg precedes elevations of serum aminotransferase activity and clinical symptoms
  2. Remains detectable during the entire icteric or symptomatic phase of acute hepatitis B and beyond.
  3. Typically HBsAg becomes undetectable 1 to 2 months after the onset of jaundice and rarely persists beyond 6 months.
  4. After HBsAg disappears, antibody to HBsAg (anti-HBs) becomes detectable in serum and remains detectable indefinitely thereafter
  5. variability exists in the time of appearance of anti-HBs after HBV infection, a gap of several weeks or longer may separate the disappearance of HBsAg and the appearance of anti-HBs : gap” or “window” period
  6. persons with anti-HBs in serum are protected against reinfection with HBV suggest that anti-HBs is the protective antibody
  7. HBsAg; its presence does not signal imminent clearance of hepatitis B.


  1. sequestered within an HBsAg coat, and is not detectable in serum .
  2. By contrast, anti-HBc is readily demonstrable in serum, beginning within the first 1

to 2 weeks after the appearance of HBsAg and

  1. Anti Hbc preceeds anti-HBs Ab by weeks to months
  2. anti-HBc may represent serologic evidence of current or recent HBV infection especially in window period
  3. blood containing anti-HBc in the absence of HBsAg and anti-HBs has been implicated in the development of transfusion-associated
  4. isolated anti-HBc does not necessarily indicate active virus replication; most instances of isolated anti-HBc represent hepatitis B infection in the remote past.
  5. Anti-HBc of the IgM class (IgM anti-HBc) predominates during the first 6 months after acute infection, whereas IgG anti-HBc is the predominant class of anti-HBc beyond 6 months.
  6. Generally, in persons who have recovered from hepatitis B, anti-HBs and anti-HBc persist indefinitely


  1. appears concurrently with or shortly after HBsAg.
  2. Its appearance coincides temporally with high levels of virus replication and reflects the presence of circulating intact virions and detectable HBV DNA.
  3. In self-limited HBV infections, HBeAg becomes undetectable shortly after peak elevations in aminotransferase activity, before the disappearance of HBsAg, and anti-HBe then becomes detectable
  4. HBeAg is a qualitative marker and HBV DNA a quantitative marker of this replicative phase,


  1. Hepatitis B antigens and HBV DNA have been identified in extrahepatic sites, including lymph nodes, bone marrow, circulating lymphocytes, spleen, and pancreas
  2. does not appear to be associated with tissue injury in any of these extrahepatic sites,
  3. explains the recurrence of HBV infection after orthotopic liver transplantation

No comments: