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Chapter: Medicine Study Notes : Gastro-Intestinal

Hepatitis B - Liver Disease

350 million with chronic infection, >75% of these Asian

Hepatitis B

 

Epidemiology

 

·        350 million with chronic infection, >75% of these Asian

·        30% of chronically infected die prematurely from the disease

·        In NZ, approx. 50,000 carriers.  Chinese 10%, Maori 5.4%, PI 4.4%, European 0.43%

·        Transmission:

o  Body fluids (blood, semen), including transfusion & contaminated needles 

o  Mother to baby (vertical transmission): 95% risk of infection – vaccinate at birth and give Anti-HBs – immune globulin

o  Organ transplant 

o  Child to child (horizontal transmission). Must get into blood – e.g. grazes, stubbed toes. Very resilient virus. Children are most likely to have asymptomatic seroconversion

 

Diagnosis

 

·        ALT elevation to 1000-1500 (usually higher than for Hep C)

·        Viral antigens:


·        Acute Viral Hepatitis due to HBV with recovery:

·        Jaundice


·        Diagnosis from bloods:

o   With HBsAg, HBeAg, and HBV DNA by PCR.

o   Acute HBV: IgM Anti-HBc

o   Carrier: HBsAg

o   Past infection: IgG Anti-HBc

o   Vaccine immunity: IgG Anti-HBs > 10 IU

·        Monitoring for carrier state: Test for HBsAg:

o   Monthly for first 6 months or until negative

o   If still positive at 6 months then probably carrier: test 6 monthly till 2 years

o   Annually thereafter

o   Also test ALT

·        Carrier infectivity:


o   Presence of HBe has a high correlation with the presence of whole hepatitis virons in the blood

 

·        Screening:



·        Normal virus called „wild type‟. Also pre-core mutant HBV virus – doesn‟t produce E antigen but will still be HBV-DNA +ive

 

Progression

 

·        Incubation 45 – 180 days

·        Symptoms:

o   Incubation: can be up to 6 months or longer

o   Minority of first episodes are symptomatic 

o   If symptoms occur: malaise, anorexia, nausea, jaundice. Coincide with appearance of Anti-HBc antibody in serum

·        Acute HBV infection leads to:

 

o   10% chronic infection („carrier‟ is a misnomer) due to ineffective immune response. 90% of infected newborn infants, 25% in young children, and 2 % adults. 25% of „carriers‟ develop chronic active hepatitis and cirrhosis, and 50% have hepatocellular carcinoma peaking in the 5th decade 

o   65% transient subclinical infection ® 100% recovery

·        25% acute hepatitis ® 99% recover, 1% ® fulminant hepatitis

·        Stages of illness:

 

o  Immune tolerant stage (mainly babies): no hepatitis even though circulating virus. HBsAg, HbeAg in blood 

o  Immune activation ® ­ALT 

o  If chronic: called chronic lobular hepatitis (CLH) or chronic active hepatitis (CAH). 6% will clear it per year. Key issue is how much fibrosis has occurred before clearance 

o  First stage of clearance:  E antigen seroconvesion.  ¯HBeAg and ­anti-HBe (was there previousl â€“  but used up too rapidly to detect.  As HBeAg¯, residual anti-HBe­)

o  Second stage: S antigen seroconversion

 

Vaccination

 

·        Most effective means of control: vaccination: Engerix B.  85 – 90% efficacy

·        Yeast derived subunit vaccine.

·        Number of notifications has dropped from 400 to 100 since introduction in 1988

·        Suspension of synthetic HBsAg 

·        Doses at 0, 1 and 6 months ® immune levels of Anti-HBs in 92%.

·        Check for seroconversion 2 months later

·        Booster every 2 – 3 years if high risk

 

Treatment

 

·        Lamivudine

o  Purine nucleoside analogue: inhibits DNA polymerase.  Potent inhibitor of HBV replications

o  As safe as placebo, no interactions, excreted unchanged

·        Each year of treatment:

o  17% HBe seroconversion (30% if concurrent interferon) 

o  15% get YMDD mutant ® ­ALT and ­HBV DNA again. But these also seem to seroconvert in time 

o  Eligibility:

§  If ALT > 2 * normal

§  Pre & post liver transplant

§  HIV and HBV co-infection (plus multi drug therapy for HIV as well)

·        Risk of Hepatocellular carcinoma – related to length of time as a carrier

 

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