case 5 - viral hepatitis

Question 1

how are hep a and e transmitted

Answer 1

faecal or oral transmission

Question 2

how are hep e b c and delta transmitted

Answer 2

via blood and bodily fluids

Question 3

what hepatitis doesnt lead to chronic infection

Answer 3

hepatitis A

Question 4

what is the pathogenesis

Answer 4

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

Question 5

what does injury of hepatocytes lead to

Answer 5

necorosis

Question 6

what can injury to bile canaliculi (cholestasis) lead to

Answer 6

Injury to bile canaliculi (cholestasis) leads to these results:
- ALP >150U/L
- Bilirubin >21umol/L

Question 7

what are the investigations for hepatitis

Answer 7

elevated ALT, AST (can be >1000U/L)
Full blood count, INR
Liver ultrasound to rule out obstruction

Question 8

describe features of viral hepatitis

Answer 8

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

Question 9

what are the non-invasive methods used to diagnose fibrosis

Answer 9

elastography and fibrotest

Question 10

what is a fibroscan

Answer 10

waves are reflected more quickly as liver ‘stiffness’ increases, I.e the liver becomes more fibrotic

Question 11

describe the complications of cirrhosis

Answer 11

progression to decompensated liver disease and hepatocellular carcinoma
Complications of portal hypertension
Ascites
Variceal bleeding
Encephalopathy
Subacute bacterial peritonitis
Acute on chronic liver failure

Question 12

what is the survival rate for decompensated liver disease

Answer 12

50% 5 year survival

Question 13

what type of virus is hep a

Answer 13

RNA virus - piconavirus

Question 14

what are complications of hep a

Answer 14

prolonged cholestasis
Liver failure
Rare but more likely in older adults with pre-existing liver disease

Question 15

diagnosis of acute hep a infection would show what

Answer 15

HAV and IgM

Question 16

diagnosis of recovery or vaccinated hep a would show

Answer 16

HAV and IgG

Question 17

what is the prevention for hep a

Answer 17

vaccine (given at 0, 6-12 months)
Immunoglobulin
Improvement in sanitation

Question 18

what type of virus is hep e

Answer 18

RNA virus - herpesvirus

Question 19

what are the different genotypes of hepatitis E

Answer 19

genotype 1,2 large ‘water borne’ outbreaks
Genotype 3,4 zoonotic, sporadic cases

Question 20

what is the diagnosis for hep e

Answer 20

HEV, IgM (hepatitis E IgG, HEV RNA blood, stool)

Question 21

what is the vaccination of hep e

Answer 21

Hecolin

Question 22

what type of virus is hep b

Answer 22

DNA virus (hepadnaviridae) with multiple subtypes

Question 23

what is the outcome of infection closely linked to

Answer 23

Outcome of infection very closely linked to maturity of immune system and effectiveness of response

Question 24

what is the epidemiology of hep b in the UK

Answer 24

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

Question 25

what are the hep b viral proteins

Answer 25

hepatitis B surface antigen - HBsAG Hepatitis B e antigen - HBeAG

Question 26

what are the anti bodies for hep b

Answer 26

hepatitis B e antibody - anti-Hbe Hepatitis B core antibody - Anti-HBc (IgM, IgG) Hepatitis B surface antibody - anti-HBs

Question 27

what does surface antigen for more than six months define

Answer 27

chronic infection

Question 28

what does everyone have prior to vaccination

Answer 28

hepatitis B surface antigen only

Question 29

interpretation of no exposure to hep b serology

Answer 29

HBV sAG negative Core Ab negative

Question 30

what would previous exposure show

Answer 30

HBV sAg negative Core Ab positive

Question 31

what would chronic infection show

Answer 31

HBV sAg positive Core Ab positive

Question 32

what are the phases for hep b infection

Answer 32

Immune tolerant Immune clearance (HBeAg-positive chronic hepatitis) Inactive carrier phase Reactivation (HBeAg-negative chronic hepatitis)

Question 33

what are these phases characterised by

Answer 33

fluctuating levels of alt and hep b virus DNA

Question 34

What is mechanism of action of tenogovir and entcavir

Answer 34

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.

Question 35

what does interferon do

Answer 35

Interferon - stimulates our immune response to recognise that these cells are infected with a virus of the hepatocytes

Question 36

why are CCC DNA hard to get rid of and how can we do so

Answer 36

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

Question 37

what is hepatitis delta virus

Answer 37

defective RNA virus that needs hep b machinery to replicate

Question 38

what does it use for envelope

Answer 38

uses surface antigen for hep b

Question 39

what are clinical features of hep d

Answer 39

severe hepatitis, 70% progress to cirrhosis Lifetime risk of HCC doubled

Question 40

how is hep d diagnosed

Answer 40

hepatitis delta IgM, IgG, HDV RNA

Question 41

how is hep d treated

Answer 41

- clearance of HBV sAG —> eradication of delta PEG IFN for >48 weeks

Question 42

what is the prevention for hep d

Answer 42

hep b vaccine

Question 43

what is hep c

Answer 43

RNA flavivirus

Question 44

what would no exposure to hep c show

Answer 44

HCV AB negative

Question 45

what would prior exposure to hep c show

Answer 45

HCV AB positive Check HNC RNA if negative

Question 46

what would chronic infection of hep c show

Answer 46

HCV AB positive HCV RNA positive

Question 47

what are direct acting antivirals

Answer 47

HCV poly protein

Question 48

what does IFN do

Answer 48

IFN stimulates immune system, direct inhibition of viral replication

Question 49

where does the life cycle take place

Answer 49

the cytoplasm

Question 50

what are the current therapies for chronic hep c

Answer 50

approval required from local MDT Combinations of DAAs in single Tabley Need to know genotype, if cirrhosis

Question 51

what are the suffixes of the drug name indicate

Answer 51

‘Previir’ = protease inhibitor ‘Asvir’ = NS5A inhibitor ‘Buvir’ = NS5B inhibitor

Question 52

what has a 98% cure

Answer 52

Velpatasvir/sofosbuvir (Epclusa) pan genotype

Question 53

what has a 90% cure

Answer 53

Elbasvir/grazoprevir (zepatier) genotype 1,4