Viral Hepatitis Flashcards
OVERVIEW
i) which hepatitis cause chronic liver disease? which two do not?
ii) are hep B and C directly cytopathic? what does this mean?
iii) can it be sub clinical?
iv) what is chronic hepatitis defined by?
i) hep B and C > CLD
hep A and E > dont progress to CLD
hep D > doesnt cause infection alone (need co infec with hep B)
ii) no - means they dont cause direct injury to hepatocytes
- it is the immune response that causes most of the injury
iii) yes - may be asymp
iv) infection for more than six months (abnormal LFTs and positive serological markers)
HISTOLOGICAL STAGING OF HEPATIC FIBROSIS
i) what happens in stage 1?
ii) what stage is cirrhosis? what will the liver look like?
i) fibrous expansion
ii) stage 5 or 6
- nodular and scarred
EPIDEMIOLOGY
i) name three areas that have high hep B
ii) name three risk factors for Hep B
iii) is it a RNA or DNA virus?
i) sub saharan africa, south east asia, north canada
ii) IVDU, MSM, HIV, migration, heathcare workers
iii) DNA virus with four overlapping open reading frames
HEP B REPLICATION
i) what is the target cell? where does it go once entered
ii) what does the DNA get transformed to?
iii) by which mechanism does transcription occur?
iv) which TLR protein is recog by PAMPs in the immune system? what does this ultimately lead to? (3)
v) what does development of Hep B surface antibodies mean for immunity? how do antibodies stop the virus?
i) hepatocytes > nucleus
ii) viral DNA enters the nuc and gets transformed to cccDNA
iii) reverse transcription of RNA intermediate
iv) TLR3
- ultimately leads to downregulation of viral synthesis, inhibition of viral replication and cell death through secretion of perforins
v) develop life long immunity (natural or imm) > neutralising Ab that forms a complex with surface antigen and stops uptake by hepatocytes
HEP B EVADING AND IMMUNITY
i) name three ways that HBV may evade immune detection
ii) once antibodies to Hep B have been developed - how long are you immune for? what type of antibody is formed and how does this confer immunity?
iii) what may be seen in relation to cell attack in early/late viral illness?
iv) what % of immunocompetent adults will have resolved Hep B infection once contracted?
i) evades detection by innate system using cccDNA
not recognised by host imm system
interferes with expression of TLR
ii) can be via immunisation or natural infection > lifelong protection
- neutralising antibody forming a complex with the Hep B antigen > prevents uptake by healthy hepatocytes
iii) early > attack with IFNs but non cytopathic (doesnt break it up)
late > cytopathic attack (breaks up and cell death)
iv) 95% of people > life long immunity
PERSISTENT HEP B INFECTION
i) what is seen in patients that get hep B through vertical transmission or in early childhood?
ii) what can happen to an immunocompromised person if there is high viral load?
iii) which IL can downreg anti viral immune responses and allow persistent infection?
i) tolerance to Hep B > can have high viral load and miminal symptoms/imm response
- supressed immune mediated elimination of infected cells > TH2
(most adults will clear virus)
ii) exhaustion of T/B cells > weak response and virus persists
iii) IL-10 (blocking can result in viral clearance - animal models)
DEVELOPMENT OF HEP B VIRUS
i) which antigen is detected first in the blood? approx how many weeks after infection?
ii) which molecule can be detected a few weeks later
iii) what two molecules will be found in the blood of someone who is immune to hep B? which one will not be found if you have only been immunised?
iv) what does hep B increase the risk of developing?
i) Hb surface antigen detectable around 4 weeks post exposure
ii) then IgM anti-Hb around week 6
iii) hep B surface antibody (HBsAB) and Hep B core antibody (HBcAB - only get this if natural sensitisation)
- if immunised - only get HB surface antibody
iv) hepatocellular carcinoma
cirrhosis
NATURAL HX OF CHRONIC HEP B
i) presence of which antigen allows classification into phases? what other level is looked at?
ii) which LFT value is used to classify? what other thing is used to classify
iii) which two characteristics are assessed when looking at chronicity
iv) what % of children will develop chronic infection after acute hep B infection? what does this increase the risk of?
v) what else should be checked for?
i) Hep B e antigen
- HBV DNA levels
ii) ALT
- is there liver inflammation?
iii) infection and heptitis
iv) 90% of children go on to develop chronic hep B (only 5% of adults do)
- increased risk of hepatocell carcinoma
- ongoing liver injury > cirrhosis > liver failure
v) hepatitis D > satellite virus and is dependent on hep B (cant exist on its own)
CHRONIC HBV TREATMENT
i) what three main medications are used?
ii) what is cure defined by?
iii) can it reactivate?
iv) what does presence of surface antigen indicate? when is it important to screen for this
i) tenofovir, entecavir and pegylated interferon
ii) cure defined by loss of HB surface antigen - rarely happens
iii) can reactivate > detect cccDNA in the liver
iv) surface antigen > active infection
- important to screen before immunosuppressive or chemotherapy
HBV CONCLUSIONS
i) what does it do to the immune response
ii) what happens early on?
iii) when does the humoral response occur? what does this reduce?
iv) which molecule prevents re infection
v) what % of immuncompetent adults clear acute infection? what % of neonates develop chronic infection
i) evades it
ii) early - priming of CD4 > CD8 cells
iii) humoral response is late > no contribution to viral clearance but reduces viral spread
iv) Hep b surface antibody prevents re infection
v) 95% immunocomp adults clear it
- 90% neonates go on to develop chronic infection
HEP C
i) what type of virus is it?
ii) what % of people go on to develop chronic infection? is there a vaccine?
iii) what type of antibodies persist in chronic hep C infection?
i) RNA virus
ii) 80% of people develop chronic infection > there is no vaccine
iii) persistent viraemia and neutralising antibodies (low levels of T cells)
HEP C CHRONICITY
i) name two properties of HC that cause it to progress to chronic infection? what happens to responding T cells?
ii) what can interfere with innate immune responses? what signalling pathway is implicated
iii) how are neutralising antibodies implicated in HC progressing to chronic infection? (3)
i) high replicative rate and high viral antigen load > CD4/CD8 cell exhaustion > cant prolif and secrete cytokines
ii) non structural proteins inhibit the innate immune response through disruption of RIG I signalling
iii) develop too slowly and too late and are short lived
PROGRESSION OF HEP C
i) what can chronic hep C progress to? what does this increase risk of?
II) name three things that are associated with increase levels of clearance and recovery (not progressing to chronic hep C)
iii) name three things that are associated with progression to cirrhosis
iv) what liver marker will spike as hep C RNA is produced?
v) what is the current treatment?
i) chronic > mod or severe can go on to develop cirrhosis
then end stage liver disease/hepatocellular carcinoma > death
ii) female, jaundice, low viral load, genotype 3, white caucasian ethnicity
iii) increased age, male, alcohol, HIV, hep B virus
iv) ALT - most replication is in cytoplasm
v) direct acting antivirals
HEP C CONCLUSIONS
i) is it directly cytopathic?
ii) what % of people go on to develop chronic disease
iii) do neutralising antibody prevent re-infection? is this the same as hep B
iv) why do so many people progress to chronic
v) which type of drugs are used and what are survival rates
i) no
ii) up to 80%
iii) neut AB doesnt prevent reinfection (it does in hep B)
iv) high replicative rate and generation of escape mutants
v) direct acting antivirals > 95% survival rates
