Viral Hepatitis (B and D) Flashcards
Define hepatitis B and D.
Hepatitis caused by infection with hep B virus (HBV) which may follow an acute or chronic (defined as viraemia and hepatic inflammation continuing >6 months) course.
Hep D virus (HDV), a defective virus, may only co-infect with HBV or superinfect persons who are already carriers of HBV.
Which virus is related to hep B?
Hepatitis D – you can only get D if you have B. two Ds make a B
Can you be infected with only HDV?
Hep D virus (HDV), a defective virus, may only co-infect with HBV or superinfect persons who are already carriers of HBV.
What type of virus is HBV? How is it transmitted?
HBV is enveloped, partially double stranded DNA virus
Transmission by sexual contact, blood and vertical transmission
Name 3 viral proteins produced by HBV. How can you tell if someone is particularly infectious?
Various viral proteins are produced including:
- core antigen (HBcAg),
- surface antigen (HBsAg) and
- e antigen (HBeAg).
HBeAg is a marker of high infectivity.
What type of virus is HDV? Which proteins does it produce?
HDV is a single-stranded RNA virus
It is coated in HBsAg (surface antigen)
Summarise the pathophysiology of hepatitis.
Antibody and cell mediated immune responses to viral replication lead to liver inflammation and hepatocyte necrosis
Histology can be variable from mild to severe inflammation and changes of cirrhosis.
What are the risk factors for HBV?
- IV drug use
- unscreened blood and blood products
- infants of HbeAg-positive mothers
- sexual contact with carriers
- genetic - factors associated with increased rates of viral clearance
What affects the risk of persistant HBV infection?
Varies with age
Babies are more likely to develop chronic carriage
How common are HBV/HDV?
- Common but HBV is relatively uncommon in UK
- 350 million worldwide infected with HBV
- Common in southeast Asia, Africa, Mediterranean
- HDV also found worldwide
What is the incubation period for HBV?
3-6 months with a 1-2 week prodrome of malaise, headache, anorexia, nausea, vomiting, diarrhoea, RUQ pain
How does HBV present?
May present at any stage:
- 1-2 week prodrome of malaise, headache, anorexia, nausea, vomiting, diarrhoea, RUQ pain
- May experience serum sickness type illness - e.g. fever, arthralgia, polyarthritis, urticaria, maculopapular rash
- Jaundice then dark urine and pale stools
- Recovery within 4-8 weeks
- 1% develop fulminant liver failure
- Chronic carriage may be diagnosed after routine LFT or if cirrhosis decompensates
What percentage of those infected with HBV develop fulminant liver failure?
1%
What are the signs of HBV/HDV on examination?
Acute -
- jaundice
- pyrexia
- tender hepatomegaly
- splenomegaly
- cervial lymphadenopathy in 10-20%
- urticaria/maculopapular rash occasionally
Chronic:
- no findings or
- signs of chronic liver disease
- decompensation
What investigations would you do for HBV/HDV?
Viral serology:
- Acute HBV - HbsAg +ve, IgM anti-HbcAg (core antigen)
- Chronic HBV - HbsAg +ve, IgG anti-HBcAg, HbeAg +ve or -ve (negative in precore mutant variant)
- Cleared HBV/immunity - anti-HBsAg +ve, IgG anti-HBcAg
- HDV infection - detected by IgM or IgG against HDV
Other:
- PCR - detects HBV DNA and is the most sensitive measure of ongoing viral replication
- LFT - ++ AST and ALT, high bilirubin, high AlkPhos
- Clotting - high PT in severe disease
- Liver biopsy - percutaneous or transjugular if clotting is deranged or ascites present
What type of immunisation is available for HBV?
Passive immunisation - Hep B immunoglobulin (HBIG) following acute exposure and to neonates born to HbeAg +ve parents (in addition to active immunisation)
Active immunisation - recombinant HbsAg vaccine for individuals at risk and neonates born to HBV +ve mothers.
Immunisation against HBV protects from HDV
How do you manage chronic HBV?
Chronic HBV Treatment
SC treatment 48 weeks duration:
- Interferon Alpha - used in a subset of patients who look like they are clearing the virus by themselves. Do not use in patients who may require a liver transplant.
Long term treatments (PO):
- Lamivudine
- Tenofovir
- Entecavir
- Emtricitabine
Liver Transplantation – requires various other treatments (e.g. immunosuppression, nucleoside analogues, hepatitis B Ig)
Liver Failure
- Antivirals are very effective in treating the viral hepatitis - usually takes ~9 months in liver failure
What are the complications of HBV/HDV?
- Fulminant liver failure in 1%
- Chronic HBV infection (~10% adults but higher in neonates) - i.e. persistence of HbsAg for 6 months or more
- Cirrhosis
- Hepatocellular carcinoma (AFP rises)
- Extrahepatic immune complex disorders e.g. glomerulonephritis, polyarteretis nodosa
- Superinfection with HDV may lead to acute liver failure or more rapdly progressive disease
What is the prognosis with HBV?
10% infections become chronic and of these 20-30% develop cirrhosis
Better prognosis with:
interferon therapy if high serum transaminases,
low HBV DNA,
active histological changes
absence of complicating disease
Should HBV prophylaxis be given in these cases?
- Vaccinated
- Partially vaccinated
- Fully vaccinated with primary course
- Known non-responder to HBV vaccines
What % of HBV infected adults go on to develop chronic Hep B?
10%
Define chronic Hepatitis B:
Persistence of HBsAg for 6 months or more after acute HBV infection
How do HBV DNA levels correspond to prognosis?
Low levels correspond with lower:
- incidence of cirrhosis
- incidence of HCC
Therefore high levels are an indication of need to treat.
Who gets the HBV vaccine?
Pre-exposure prophylaxis
- Routine childhood immunisation in the UK since 2017
- High risk population
Post-exposure prophylaxis
- Neonate born to mother living with hepatitis B
- Sexual partner: HBV vaccine +/- HBIG (within one week from the contact)
- Needle stick injury
Describe the virology of HDV.
Single-stranded, defective, circular RNA genome virus that relies on HBV for replication
Smallest virus known to infect man
Incubation 3-6 weeks
Blood-borne transmission
What are the two patterns of infection with HBV-HDV and which is worse?
- HBV-HDV coinfection
- Getting both B and D at the same time
- Similar to classic acute HBV - causes elevated ALT and IgM anti-HDV at the same time as symptoms; mostly self limited
- Gives acute HBV (<5% progress to chronic)
- HBV-HDV superinfectioin
- When you already have B and you get D.
- 80% risk of chronic infection
- Increased risk of cirrhosis and HCC than chronic hep B alone
What is the management of HDV?
Treatment: PEG-interferon alpha is licensed for HDV superinfection in CHB
Prevention: pre-exposure HBV immunisation
