About
- In UK 180,000 are infected with HBV
- Many are asymptomatic and unaware
- Worldwide 1-2 million deaths per year
Aetiology
- Hepatitis B is a highly infectious dsDNA virus
- Commonly found in Middle East, Asia, Africa
- Mutations in the HBV genome alter the clinical expression
Infection from
- Infected blood products, Sharing contaminated needles, Sexual transmission
- Mother to baby "vertical transmission" (HBeAg +ve mothers)
Virology
- Antigens : only sAg and eAg are detectable
- Antibodies to sAg, cAg and eAg
Serology
Ag/Ab | Comments |
Surface sAg | Protein on surface of HBV. Earliest signs of HBV infection found 27-41 days even within incubation period of infection. Marks acute or chronic infection. Usually disappears. Persistence after 6 months suggests carrier. Remains negative with HBV vaccination. HBsAg is used to make HBV vaccine |
Core cAg | Core antigen. Not detectable in blood |
Envelope eAg | Seen in acute infection. Indicates active viral replication and infectivity. May not be detectable in those with precore mutations. Also suggests chronic infection if persists. Suggests infectious. |
IgG anti-sAg | Suggests clinical recovery and immunity to HBV either following infection or immunisation. If also HBsAg then suggests recovery and immunity |
IgM anti cAg | IgM denotes recent infection within 6 months. |
IgG anti-cAg | IgG denotes previous infection. Found in Convalescent period from sAg+ to development of Ant-sAg |
State
State | HBsAg | anti-HBc | anti-HBs | IgM anti-HBc |
---|
Susceptible to infection | Negative | Negative | Negative | Negative |
Immune to natural infection | Negative | Positive | Positive | Negative |
Immune to Hepatitis B vaccination | Negative | Negative | Positive | Negative |
Acutely infected | Positive | Positive | Negative | Positive |
Chronically infected | Positive | Positive | Negative | Negative |
Serological Chronological course
- Infection, DNA replication, Incubation 4-12 weeks, HBsAg +, ↑ AST/ALT
- Acute hepatitis : Ag +, eAg +, IgM cAg +, IgG cAg +
- Acute/Seroconversion : sAg +, IgM cAg +, IgG cAg +, IgG eAg +
- Immune : IgG cAg +, IgG eAg+, IgG sAg +
Course
- Chronic infection is seen in 10% of hepatitis B infections
- Acute hepatitis is seen in 25% of those with HBV infection
- Asymptomatic infection in 65% with formation of HBsAb
Acute Hepatitis
- Incubation period 2-6 months. 70 percent of patients subclinical
- Fever, malaise, rash, small joint polyarthritis, distaste for cigarettes
- Jaundice and pale stool, Recovery over 6 weeks
- ↑ ALT and AST and HBsAg +ve, IgM Anti-Hbc
- No IgG Anti-Hbc, Possibly HBeAg and HBV-DNA
- Supportive management
- Recovery suggested by HBsAg negative and antibodies to HBsAg
- Mortality < 1% with Fulminant liver failure
- Resulting Serology is Anti-HBsAg, IgG Anti-HBcAg, Possibly Anti-HBe
- 10% will go on to develop chronic disease
Risks for developing chronic infection
- Low age e.g. Vertically infected infants
- Genetic factors
Chronic Infection 10% (ALT > 6 months)
- HBsAg +ve, IgG Anti-Hbc, Possibly HBeAg, Possibly Anti-HBe, HBV-DNA positive
- HBeAg and HBV-DNA denotes highly infectious and risks of cirrhosis and hepatocellular carcinoma
- Treat those at risk of cirrhosis and malignancy
- High risk = HBsAg surface antigen persists, HBeAg antigen detectable unless mutant virus, HBV-DNA detectable, HBsAg seen as Ground glass appearance on H&E staining of hepatocyte
Prevention
- Avoidance of needle sharing, prostitutes, unprotected sex particularly homosexual
- Immunisation of high risk e.g. health care workers, addicts, dialysis patients
- Active and passive immunisation to non-immune needlestick injuries and babies of HBsAg positive mothers
Serology summarised
State | sAg | IgG sAb | IgM cAb | IgG cAb | eAg | eAb | HBV DNA |
Acute Hepatitis | + | - | + | - | + | - | + |
Resolved Acute Infection | - | + | - | + | - | + | - |
Chronic Carrier | + | - | - | +/- | - | + | - |
Chronic Active hepatitis | + | - | - | +/- | + | - | + |
Chronic Active Precore variant | + | - | - | +/- | - | + | + |
Immunised | - | + | - | - | - | - | - |
Management
- Those with detectable HBsAg and clinical or other actors suggesting chronic infection can be considered for treatment without waiting 6 months. Those with high serum HBV DNA (≥ 20,000 IU/ml) and elevated ALT should be treated. There is a strong correlation between fibrosis and hepatocellular carcinoma.
Antivirals
- Pegylated Alpha-2b interferon 100 mcg once weekly s/c for 4 months. Flu-like illness malaise, headaches. The disappearance of HBeAg in 40%. Less useful in those HBeAg negative. Useful in those with elevated ALT and AST. Not used in decompensated liver failure. Not for those with normal ALT or AST
- Entcevir and Tenofovir are nucleotides that suppress viral replication. This can reduce fibrosis.
- Less used now due to resistance is Lamivudine 100 mg od 1 year : Inhibits DNA polymerase and reduces HBV-DNA, More useful in those who acquired Hepatitis B perinatally or in childhood. Used in those with the decompensated disease, Used in those HBeAg negative
- Adefovir dipivoxil 10 mg/day 1 year: Used to treat mutants that themselves cause a hepatitis
- Liver transplantation is becoming more possible with the use of antivirals. In the past, the new liver was reinfected with Hepatitis B.
- HBeAg-negative CHB represents a late phase in the natural course of chronic HBV infection that develops after HBeAg loss and seroconversion to anti-HBe. A mutation in the precore genome of the virus can lead to a (HBeAg)-negative Chronic Hepatitis B infection. They are HBeAg-negative and anti-HBe-positive and there are signs of high viral replication and active disease. It is a severe and progressive form with frequent development of cirrhosis and HCC. Treat if the ALT is elevated and there is evidence of increased viral replication.
References