case 5 - viral hepatitis Flashcards
how are hep a and e transmitted
faecal or oral transmission
how are hep e b c and delta transmitted
via blood and bodily fluids
what hepatitis doesnt lead to chronic infection
hepatitis A
what is the pathogenesis
hepatitis viruses: non-cytopathic
Hepatocyte damage is immune-mediated
Antigen recognition by cytotoxic T cells: apoptosis
Chemokine driven recruitment of Ag-nonspecific cells
depending on strength of immune response
Mild inflammation to massive necrosis of the liver
‘Fulminant’ hepatitis which is a cause of acute liver failure
what does injury of hepatocytes lead to
necorosis
what can injury to bile canaliculi (cholestasis) lead to
Injury to bile canaliculi (cholestasis) leads to these results:
- ALP >150U/L
- Bilirubin >21umol/L
what are the investigations for hepatitis
elevated ALT, AST (can be >1000U/L)
Full blood count, INR
Liver ultrasound to rule out obstruction
describe features of viral hepatitis
sequelae of ongoing inflammation —> liver fibrosis
Progression of fibrosis to cirrhosis (20-30 years)
Accelerated by co factors - alcohol, HIV, diabetes, steatohepatitis
Asymptomatic, until liver decompensation
what are the non-invasive methods used to diagnose fibrosis
elastography and fibrotest
what is a fibroscan
waves are reflected more quickly as liver ‘stiffness’ increases, I.e the liver becomes more fibrotic
describe the complications of cirrhosis
progression to decompensated liver disease and hepatocellular carcinoma
Complications of portal hypertension
Ascites
Variceal bleeding
Encephalopathy
Subacute bacterial peritonitis
Acute on chronic liver failure
what is the survival rate for decompensated liver disease
50% 5 year survival
what type of virus is hep a
RNA virus - piconavirus
what are complications of hep a
prolonged cholestasis
Liver failure
Rare but more likely in older adults with pre-existing liver disease
diagnosis of acute hep a infection would show what
HAV and IgM
diagnosis of recovery or vaccinated hep a would show
HAV and IgG
what is the prevention for hep a
vaccine (given at 0, 6-12 months)
Immunoglobulin
Improvement in sanitation
what type of virus is hep e
RNA virus - herpesvirus
what are the different genotypes of hepatitis E
genotype 1,2 large ‘water borne’ outbreaks
Genotype 3,4 zoonotic, sporadic cases
what is the diagnosis for hep e
HEV, IgM (hepatitis E IgG, HEV RNA blood, stool)
what is the vaccination of hep e
Hecolin
what type of virus is hep b
DNA virus (hepadnaviridae) with multiple subtypes
what is the outcome of infection closely linked to
Outcome of infection very closely linked to maturity of immune system and effectiveness of response
what is the epidemiology of hep b in the UK
UK prevalence = 0.3%
Most new infections occur in adults, by sexual or parenteral route
Screwing programmes: identify non-immune, and chronic infection
antenatal clinical (Mother HBV sAG +ve)
Vaccination of baby +/- Ig
Prisons
GUM clinics, community drug services
what are the hep b viral proteins
hepatitis B surface antigen - HBsAG
Hepatitis B e antigen - HBeAG
what are the anti bodies for hep b
hepatitis B e antibody - anti-Hbe
Hepatitis B core antibody - Anti-HBc (IgM, IgG)
Hepatitis B surface antibody - anti-HBs
what does surface antigen for more than six months define
chronic infection
what does everyone have prior to vaccination
hepatitis B surface antigen only
interpretation of no exposure to hep b serology
HBV sAG negative
Core Ab negative
what would previous exposure show
HBV sAg negative
Core Ab positive
what would chronic infection show
HBV sAg positive
Core Ab positive
what are the phases for hep b infection
Immune tolerant
Immune clearance (HBeAg-positive chronic hepatitis)
Inactive carrier phase
Reactivation (HBeAg-negative chronic hepatitis)
what are these phases characterised by
fluctuating levels of alt and hep b virus DNA
What is mechanism of action of tenogovir and entcavir
they block a viral enzyme called hepatitis B DNA polymerase and switch off the replication in the cell. They do not eradicate the CCC DNA though.
what does interferon do
Interferon - stimulates our immune response to recognise that these cells are infected with a virus of the hepatocytes
why are CCC DNA hard to get rid of and how can we do so
Covalently closed circular DNA is inserted into the host genome and it sits like a viral reservoir
It is very difficult to get rid of this with out current treatments for hepatitis B
Only can get rid of this CCC DNA is by getting rid of the whole hepatocyte
what is hepatitis delta virus
defective RNA virus that needs hep b machinery to replicate
what does it use for envelope
uses surface antigen for hep b
what are clinical features of hep d
severe hepatitis, 70% progress to cirrhosis
Lifetime risk of HCC doubled
how is hep d diagnosed
hepatitis delta IgM, IgG, HDV RNA
how is hep d treated
- clearance of HBV sAG —> eradication of delta
PEG IFN for >48 weeks
what is the prevention for hep d
hep b vaccine
what is hep c
RNA flavivirus
what would no exposure to hep c show
HCV AB negative
what would prior exposure to hep c show
HCV AB positive
Check HNC RNA if negative
what would chronic infection of hep c show
HCV AB positive
HCV RNA positive
what are direct acting antivirals
HCV poly protein
what does IFN do
IFN stimulates immune system, direct inhibition of viral replication
where does the life cycle take place
the cytoplasm
what are the current therapies for chronic hep c
approval required from local MDT
Combinations of DAAs in single Tabley
Need to know genotype, if cirrhosis
what are the suffixes of the drug name indicate
‘Previir’ = protease inhibitor
‘Asvir’ = NS5A inhibitor
‘Buvir’ = NS5B inhibitor
what has a 98% cure
Velpatasvir/sofosbuvir (Epclusa) pan genotype
what has a 90% cure
Elbasvir/grazoprevir (zepatier) genotype 1,4
