hepatitis virus Flashcards
what are the most common hepatitis viruses
- hep b
- hep a
- hep c
- hep d (delta agent)
- hep e
what is the biology of the hep a virus
- spherical non enveloped virus of 27nm
- single stranded RNA genome
- exceptional stability
what is the basic form of a virus
- protein coat with either DNA or RNA
- can only grow in cells, not in an agar plate
what is the transmission and epidemiology of hep A
- mainly transmitted through focal-oral route (can also be blood borne)
- person-person, food borne and water borne
- commonly follows food poisoning from sea food
- in developed countries, 20-50% of adult’s have antibody
- in developing countries >90% have antibody
what are the clinical features of hep A
- incubation period is 2-7 weeks
- many subclinical infection s
- illness usually brief and self limiting
- mortality <0.2% = very rarely die from it
- no chronic disease
what is the diagnosis of hep A
- demonstration og HAV antigen in faeces
- serology - detection of IgM and anti-HAV
what is serology
take blood from individual and look for antibodies
what is the immunisation of hep A
- passive or active
- passive = give preformed antibodies (short term)
- active = give antigen and body makes antibodies
- human normal immunoglobulin = short term protection (4 months) - passive
- vaccine = formaldehyde inactivated, prepared from the GBM of HM 175 strain of HAV, single dose will give antibody for a year, then booster does at 6-12 month gives 10 years immunity, active
is hep a preventable
yes - it is an eminently preventable disease
how many people are affected with hep b worldwide
350 million globally
what age is hep b most prominent
70% of new cases are in 15-39 y/o
how much more infectious is hep b than HIV
more than 100x more infectious
- only take a tiny amount go blood from an infected individual to cause you infection
is there a curative treatment
no, but new antivirals suppress the viral load
- been big strides in recent years in suppressing the viral load
what is the viral load
- nor of virus particles in 1 ml of blood
- lower load = better
what genome does hep b have
- DNA virus
- partially double stranded DNA virus
what family of viruses does hep b come from
- hepadnavirus
- family of DNA viruses with a unique life cycle involving an RNA intermediate ad use of a viral polymerase with reverse transcriptase activity
- cause liver damage
- hep B is best known virus from family
what is the intact part of the hep b virus
- dane particle
- viral code and genome in the centre
how many subtypes of hep b exist
8
what is the structure of hep b
- has hep b surface antigen (HBs Ag)
- has dna polymerase
- has dna in centre
- has hep b core antigen
- has protein kinase
what forms the protein coat of the hep b virus
hep b surface antigen
- forms excessive amounts of this
what is the concept of the vaccine
- produce antibodies against the coating to protect you
where is the highest prevalence of hep b
Africa mainly and Asia
- have >8% people have it here
where has an intermediate prevalence of hep b
russia, india, top of Africa
- 2-7% of population
where has low prevalence of hep b
uk, america, australia, netherlands
- <2% of population
in 2018 what were the lab reports of hep b in England
- 381 acute or probable cases
- incidence = 0.68/100,000
- highest incidence was in London = 64.7%
- many people do not know they have it or that they carry the virus
how is hep b transmitted
- 3 main routes
- blood borne, sexual or perinatal
what are examples of people wit higher risk of hep b
- iv drug users
- sexually active people
- children of immigrants from disease-endemic areas
- infants born to infected mothers (perinatal)
- healthcare workers
- haemo-dialysis patients
what is perinatal spread of hep b
- mother can transmit to infant
- important in pairs of the world where hep b is endemic
- if you are infected as a child you are more likely to be a carrier = have it for many years and will infect others
what is the epidemiology of hep b in non-endemic areas (UK)
- 80% inapparent disease, 20% acute hepatitis
- 95% recovery, 5% chronicity (most are adults)
- can lead to cirrhosis and liver cancer
what is the epidemiology of hep b in endemic areas (Asia)
- mostly inapparent disease
- 5-20% recovers, 80-95% chronicity (most are infants)
- can lead to cirrhosis and liver cancer
what is the risk of chronic hep b by the age of acquisition and immune status
- neonates = 90-100%, very high risk of becoming a carrier
- children = 20-40%
- immunosuppressed = 21%, high risk of becoming a carrier
- adults = <5%
what are possibly outcomes of exposure to hep b
- infection (65% subclinical)
- this can the lead to :
- death from fulminant hepatitis (1%)
- persistent infection HBs Ag for >6 months (5-9%)
- recovery with immunity (90-95%)
what happens if you are given the antigen of hep b and don’t develop antibodies in first 6 months
- you are likely to be a carrier = chronic
if someone is making a normal recovery from hep b what antibodies will they have
- IgG anti HBc
- IgM anti HBc
- Anti HBe
- Anti HBs
- amount of antigens of these will decrease and eventually there will be none (within 2-3 months)
what antibodies show you are making recovery from hep b
HBe and HBs
what happens if you are a chronic carrier of hep b
- will only form antibodies IgG anti HBc and IgM anti HBc
- no anti HBe or anti HBs ( so antigens HBe and HBs do not disappear an are still present month or years later
what people are risks to others in hep b
chronic carriers
what is passive immunisation of hep b
- hep b immunoglobin (give if person not responding to vaccine)
- from pooled plasma
- main use is single acute exposure in non-immune individual
- administer within 48hrs of infection
- highly immunogenic
what is the HBV vaccine
- highly immunogenic
- no booster dose is required for persons who have responded to HBV vaccine (if responded once and have antibody, you will be protected even if antibody amount decreases)
what did the WHO recommend in 1992 which helped hep b
- they suggested that the HBV vaccine become integrated into national immunisation programmes of all highly endemic countries
- was done in Taiwan and it had a good response
- in theory if this vaccine was universally given, hep b could be eradicated
what is the active immunisation of hep b
- vaccine = hep b surface antigen absorbed on aluminium hydroxide adjuvant
- produced by recombinant DNA technology
- protection = good
- response = not always good, need to check antibody levels
- vaccine administration =intramuscular
- 3 doses required = time zero, one month and six months
- post immunisation = test for antibody response 2-4 months after vaccine course completed
what is the average volume of blood inoculated in needle stick injury and how many virus particles could that contain of hep b
- with a 22 gauge needle, 1microlitre of blood is inoculated
- this can contain 100 infectious doses of HBV
- a non-responder to the vaccine had a 1 in 3 chance of becoming infectious from this injury
what is the risk of hep b post exposure prophylaxis
- in vaccine responders there is no risk
- in vaccine non-responders = in the occupational setting, hep b immune globin provides estimated 70-75% protection from HBV infection
how can you treat chronic HBV infection
- goal of therapy = sustained viral suppression
- agents available = immunomodulatory agents (inferon alpha and pegylated interferon
= nucleoside analogues - telbivudine, entecavir
= nucleotide analogues - adenovirus and tenofovir, suppers viral load to level at which they’re not deemed to be a risk
when was hep c discovered
in 1989 and was originally called non-a non-b hepatitis
what type of virus is hep c
- flavivirus family = related to these
- blood borne
how many genotypes does hep c have
6
- not just one virus, 6 genotypes behave differently
how many people worldwide are infected with hep c
200 million
- fro every 1 person with HIV, 4 have hep c
is a vaccine available for hep c
no
- can be seen as a bigger is than hep b
- treatments have improved but are expensive
what genome is hep c
RNA virus
how big is the hep c virus
30-38nm
- morphology unknown
can hep c be grown in culture
no, needs serology to diagnose
what is the global prevalence of hep c
- high in Asia, top of Africa = >3.5%
- moderate in UK, Europe, most of Africa = 1.5-3.5%
- low in USA, Canada = <1.5%
how is the prevalence of chronic infection of hep c changing
- decreasing steadily
- 143,000 in 2015 in England, 113,000 in 2018
what is the main risk factor for hep c in developed countries
intravenous drug use
- significant number of people with hep c don’t know they have it
when is someone no longer infectious with hep c
once they have been treated, doesn’t cure them but means they are no longer infectious to others
how is hep c diagnosed
- serologically
- anti-HCv test = detects presence of antibodies, indicates exposure to HCV
- HCV-RNA test = identifies presence of virus in blood, indicates active infection, main test
- viral load/quantitative HCV test = measures number of viral particles in peripheral blood
- viral genotyping = additional test, determines type of HCV present, treatments needs to be focused around type
what is the clinical course of hep c
- incubation = average incubation is 6-12 weeks, average seroconversion period =15 weeks
- acute infection = clinically mild (sub-clinical, high amount of chronic carriers), jaundice in 25% of patients
- chronic hep c = high frequency (60% of the infected), most cases preceded by clinically apparent infection, slowly progressive over 20 years
what is seroconversion
time a specific antibody develops and become detectable in the blood
what is the long term risks of hep c
like hep b, long term risks could be liver cancer and cirrhosis
- link with hepatocellular carcinoma
what is the natural history of hep c
- exposure (acute phase) = 25% become resolved
- 75% non resolved become chronic = 80% of those stay stable
- other 20% who didn’t stay stable develop cirrhosis = 75% of those become slowly progressive
- other 25% the have liver failure, transplant and death
what can help hep c disease get worse
HIV and alcohol
how long does it take from exposure of hep c to liver failure
- could take up to 25 years
- is often called the silent disease
what is the treatment of hep c
- interferon alpha in combination with ribavarin
- plus boceprevir or telaprevir (HCV protease inhibitors)for genotype 1
- self injected
what were the problems with interferon alpha alone as a treatment of hep c
- caused depression in patients
what has improved by adding rubivarin and protease inhibitors to the interferon in hep c treatment
- depression in patients was massively reduced
what do protease inhibitors do in hep c treatment
stop proteases breaking up protein chains to make viral chains so new chains couldn’t be made
what are second generation protease inhibitors used in hep c treatment
- sofosbuvir
- ledipasvir
how many people are cured from hep c
- 98%
- these newer drugs begin formed for treatment means the long term risk fo hep c aren’t a risk anymore
- also means health workers infected can go back to work
what is another name for hep d
delta agent
what type of genome does hep d have
rna virus
when can hep d replicate
only with hep b present
why can hep d only replicate when hep b is present
- as delta agent relies on hep b producing the protein coat as it can’t do it itself = the coat allows it to attach to liver cells
how is hep d transmitted
- blood borne virus
- parental and sexual routes
- co-infection or supra-infection with hep b
what is supra infection
when you already have hep b and then hep d then cause infection
- has a low chance of recovery compared to co-infection which has a high recovery
how do you treat hep d
if have hep b vaccine then cant get hep d
what are the risks of hep d
same risks as in hep b
what is hep e like
largely mimics hep a
- transmitted focal-orally
what is the biology of hep e
- spherical non-enveloped virus (32-34nm)
- single stranded RNA genome
- calcivirus like
- can’t grow in tissue culture
what is the transmission and epidemiology of hep e
- epidemic and sporadic forms
- mainly in India, Africa, Asia (not really in UK)
what are the clinical features of hep e
- incubation period is 2-9 weeks
- mainly young adults affected (15-40)
- usually self-limiting acute disease
- high mortality in pregnancy (205) due to lower immunosuppression
- no chronic disease
