Makindo Medical Notes.com

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

State

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

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

• NICE Guidelines
• Hepatitis B WHO