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Hepatitis B (Chronic Disease (HBsAg + > 6 months) (Most patients remain…
Hepatitis B
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Pathogenesis
The virus replicates in the liver and virus particles, as well as excess viral surface protein, are shed in large amounts into the blood. Viraemia is prolonged and the blood of infected individuals is highly infectious. The host immune response to the virus is responsible for hepatocellular damage.
Hepatitis B either clears spontaneously after acute infection, or becomes chronic. Age is a determining factor.
Incubation period is long: 30-180 days, average 75 days
Asymptomatic infections occur frequently, especially in the very young (< age 5), who tend to develop immunotolerance and therefore a lesser immune response to the virus, this results in decreased inflammation in the liver, as well as a higher rate of chronicity
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Approximately 5% of adults develop a chronic infection (in 95% the infection clears spontaneously and does not result in chronic infection), whereas 90% of infants infected vertically go on to chronicity.
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Acute hepatitis B may be asymptomatic or symptomatic (nausea, vomiting, anorexia, right upper quadrant pain, and jaundice)
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Fulminant hepatitis: This is a complication of acute infection. Rare; accounts for 1% of infections.
Diagnosis
Viral antigens:
- Surface antigen (sAg): surface (envelope) protein of the dane particle secreted in excess into the blood as 22 nm spheres and tubules presence in serum indicates that virus replication is occurring in the liver
- e antigen (eAg): secreted protein; shed in small amounts into blood presence in serum indicates that a high level of viral replication is occurring in the liver. May be negative in carriers with mutations in the e antigen gene who nonetheless have high level viraemia.
- Core antigen (cAg): core protein present in infected liver cells, not found in blood
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Antibody response:
- Surface antibody (sAb, antiHBs): becomes detectable late in convalescence following resolution of infection, remains detectable for life; not found in chronic carriers; indicates immunity
- e antibody (eAb, antiHBe): becomes detectable as viral replication falls in a carrier, it indicates low infectivity
- Core IgM: rises early in infection indicates recent infection
- Core IgG: Rises early present for life in both chronic carriers as well as those who clear the infection indicates exposure to HBV usually tested as total core antibodies, and implies IgG in the absence of IgM
HBV Viral load
- HBV viral load measures level of HBV DNA in blood. This is the most reliable marker of infectivity. It is more reliable than e antigen which can be negative in some carriers due to mutations in the e antigen gene
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Prevention
Active Immunization: Four types of vaccine are available
- Serum derived: prepared from s Ag purified from the serum of HBV carriers
- Recombinant sAg: made by genetic engineering in Saccharomyces cerevisiae, also known as Brewer's yeast third generation vaccines genetically engineered producing different size surface antigens. These vaccines are not available in South Africa
- Combination vaccines: vaccines containing HBV vaccine in addition to vaccines against other organisms, e.g. Hepatitis A+B
- All these vaccines are equally safe and effective. Three doses induce protective levels of antibodies in 95% of vaccine recipients. Universal immunization of infants was introduced in April 1995. Infants receive three doses: at 6, 10 and 14 weeks. However, if their mother is known to be chronically infected, they receive doses at birth, 1 month, and 6 months if their birth weight is >2kg, and an additional dose at 2 months if their birth weight is <2kg.
In addition, vaccine should be administered to people at high risk of infection with HBV:
- Health care workers
- Sexual partners of chronic carriers
- Infants of HBV carrier mothers
- Post exposure prophylaxis
Passive Antibody
Both Hepatitis B immune globulin and vaccine should be administered to non immune individuals following single episode exposure to HBV-infected blood.
Epidemiology
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Hepatitis B is parenterally transmitted (i.e. not through the gut):
- Sexual intercourse: the predominant form of spread in adults
- Horizontal spread: spread amongst children and in families. This is the most common mode of transmission in areas of high HBV prevalence, where infection is acquired early in life. In South Africa, there is a high rate of infections in children in the three to nine year age group. Also accounts for transmission in mental institutions and children's homes.
- Vertical transmission:
- Perinatal transmission from a carrier mother to her baby
- Transplacental (rare)
- During delivery
- Passed from mother to child in the post natal period via breast feeding and/or close contact
- Transmission in South East Asia.
- Blood
- Blood transfusions, serum products
- Sharing of needles, razors
- Tattooing, acupuncture
- Renal dialysis
- Organ donation
- Note: these are rare today due to advances in screening blood and organ donors, and sterile medical techniques.
- In South Africa, infection is much commoner in rural communities than in the cities.
Treatment
Acute
- supportive
- IFN-a dangerous
Chronic (For HBeAg +ve carriers with chronic active hepatitis?)
Two classes of drugs are used to treat chronic HBV infection
- Interferons
- Interferon α2a
- Pegylated interferon α2a
- Interferon-α enhances the host immune response to HBV and improves immune control of the virus. Clearance of infection (and immunity) is the best outcome, but is achieved in only around 25% cases (after a six month course of treatment). Interferon is the best available treatment for chronic HBV, but side effects and expense limit its use. Even small doses of IFN can lead to worsening liver failure and severe infections
- Nucleoside reverse transcriptase inhibitors
- These drugs interfere with viral replication, but cannot clear HBV infection. They need to be taken life long (as for HIV) to control infection..
- Lamivudine (3TC, LAM)*
- Tenofovir (TDF)*
- Entecavir (ETV)
- Adefovir (ADV)
- Telbivudine (LdT)
- Clevudine (CLV)
- Emtracitabine (FTC)*
Note: * also used to treat HIV
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