Hepatitis Flashcards
What are complications of Hep A
Fulminant liver failure (0.1% but increases with age and co-morbidites)
Viral relapse - common, occurs around 8 -9months after recovery
Mortality rate 1% over age of 40
Cholestasis following infection - higher chance if on OCP or HRT
Treatment of hep a
Supportive only Admission to hospital for severe disease - elderly - coagulopathic - severe jaundice - inability to keep down oral intake
Prevention with vaccine
How does the hepatitis b virus differ from the other hepatitis viruses?
DNA virus
- all other viruses are RNA viruses
What is the significance of genotypes of hep B
Not routinely tested
8 different genotypes
Only role is that genotype A patients who are HBeAg positive have a better response to interferon treatment
What are the main routes of transmission of hep B
High prevalence areas (SE Asia, subsaharan africa, china)
- perinatal transmission (vertical)
- horizontal transmission during childhood
Low prevalence areas
- IVDU
- sexual contact
- transfusion of blood pre-screening era
Clinical presentation of acute hepatitis B
70% sub clinical hepatitis
30% icteric hepatitis
Prodrome - rash, fatigue, fever, arthritis, arthralgia usually precedes jaundice, RUQ pain
0.5% present with fulminant liver failure
What is the serology of hepatitis A
IgM HAV develops 4-12 weeks after aquiring virus and persists for around 20 weeks
IgG HAV develops around 4-12 weeks and persists for life and confers life long immunity
Blood tests in acute hepatitis B
Raised transaminases (usually around 1000-2000, ALT higher then AST) Raised PT/INR (indicates severity) Elevated bilirubin HBsAg positive IgM anti-Hbc positive HBV DNA positive HBeAg positive
What is meant by the window period in acute hep b
When the HBsAg disappears but the anti-Hbs is yet to be at the level of detection
The only positive marker at this time of infection will be IgM-antiHbc
This period is more common in fulminant hepatitis as the virus is cleared rapidly by the immune system
What blood tests indicate recovery in acute hep b
Normalisation of transaminases in 1-4 months
HBsAg seroconverts to anti-HBs
HBeAg seroconverts to anti-HBe
Disappearance of HBV DNA
What is the rate of progression to chronic hep b and what does it depend on
Depends on age of acquisition of the virus
- perinatal 90% progression to chronic
- 1-5 years 20-50%
- adult less than 5%
What is the treatment for acute hep b
Mainstay of treatment in adults is supportive - as risk of chronic infection less then 5%’and risk of fulminant hepatitis 1%
Treatment can be offered in immunosuppressed, fulminant liver failure (need to clear virus pre-transplant), older age, underlying liver disease, hep c or d co-infection or severe disease
If drug treatment is required for acute hep b what agents are used
In general tenofovir, abacavir, entecavir etc
Interferon avoided in acute hepatitis as can worsen liver necro-inflammation
What is the goal and usual duration of treatment in acute hep b
Goal is seroconversion of HBsAg to anti-HBs
Short duration of treatment usual required
Need to check for resolution 2 tests for HBsAg 4 weeks apart before stopping
What are the 2 most common extra-hepatic manifestations of chronic hep b
Polyarteritis nodosa
Glomerular disease - nephrotic most common, membranoproliferative next
What are the 5 phases of chronic hep b infection
Immune tolerance Immune clearance Immune control Immune escape Resolution
What is the immune tolerance phase
Almost exclusively in those with perinatal acquisition
Virus is free to replicate without any recognition from immune system due to underdeveloped immune system
HBeAg positive, high levels of HBV DNA
Normal transaminases as no killing off of infected hepatocytes
Low rate of spontaneous clearance of HBsAg
Generally lasts 10-20 years
Treatment not effective in this phase due to low immune response
What are the 2 markers of HBV infectivity and replication
HBV DNA
HBeAg
What is the immune clearence phase
The initial phase in those affected as adults (don’t have an immune tolerance phase as immune system is mature)
When immune system recognises virus and starts to kill infected hepatocytes
Spontaneous HBeAg seroconversion increase to 10-20% per year
Fluctuating transaminases and liver fibrosis is seen
Treatment is effective in this phase as it enhances HBeAg seroconversion and prevents longer time in this phase (without treatment 5-6 years) therefore reducing liver damage
What is the immune control phase
Aka chronic carrier state
After HBeAg seroconversion ALT returns to normal HBV DNA levels drop and there is minimal fibrosis
Treatment is not effective in this phase as immune response is minimal
Confirmation of this phase is by 3x ALT levels and 3x HBV DNA levels (both negative) over 12 months
What is immune escape phase
Caused by selection out of mutated viruses that do not express HBeAg (ie pre-core)
See fluctuating HBV DNA and ALT levels despite HBeAg negative
Progression of fibrosis
Treatment is indicated to control viral replication
What is meant by resolution of chronic hep b
Spontaneous seroconversion of HBsAg to anti-HBs
Annual rate of clearance in western populations 0.5%-2%, asian 0.1-0.8%
Seroconversion does not preclude the development of cirrhosis or HCC especially when it occurs over the age of 50
What are some poor prognostic factors for chronic hep b
Etoh use Co-infection with hep c or d HBV variants (core-promoter or pre-core mutant) Longer time HBeAg positive Higher HBV DNA levels
What is meant by pre-core mutant HBV
Mutated hep b virus which has a mutation at gene 1896 which creates a stop codon which prevents development of HBeAg
What is a core- promoter mutant HBV
Paired mutation which leads to reduced HBsAg, not complete absence as in pre-core
What is the clinical significance of pre-core mutant HBV
More aggressive disease
Lower rates of spontaneous HBeAg seroconversion
Treatment aim instead of being for HBeAg seroconversion is to suppress viral load, often needed life-long (don’t use drugs with high rates of resistance)
Mutations are selected out throughout illness, they don’t occur in de novo disease
Who are at risk for re activation of hep b with immunosuppression
Highest risk - those who are HBsAg positive
Lower but risk with Rituximab and HSCT are those positive for anti-HBc but negative for HBsAg (theoretically have “cleared” the virus but still have very low levels of virus)
Treatment and duration of treatment to prevent re-activation
Duration is to continue 6 months after immunosuppression is stopped (12 months with Rituximab as longer to re-constitute immunity)
Options are lamivudine, tenofovir, entacavir
Interferon is avoided in acute hepatitis due to increased liver inflammation
What needs to be considered when treating lamivudine resistant patients with hep b
Entacavir shouldn’t be used as there are also high rates of resistance among lamivudine resistant patients
What does screening patients for hep b prior to immunosuppression involve
Initially test HBsAg and anti-HBc
If either positive then test HBV DNA, anti-HBs, HBeAg and anti-HBe
What are the aims of treatment with hep b
Serological aim
- HBeAg positive = promote HBeAg seroconversion
- HBeAg negative chronic hepatitis = suppress HBV DNA
To reduce progression to cirrhosis, HCC and reduce transmission
What are some treatment options for hep b and pros and cons
Interferon - heaps of side effects but only finite course of treatment
Lamivudine - good for HIV co infection, high resistance
Abacavir - minimal resistance but slower anti-viral activity
Entecavir - high rates of resistance in lamivudine resistance patients
Tenofovir - generally first line, low resistance
Indications for treatment of hep b
Acute liver failure
Complications of cirrhosis
Cirrhosis or fibrosis with elevated HBV DNA
Prevention of re activation
In pregnancy with high viral load
Extra-hepatic manifestations of hep b
HBeAg negative chronic hepatitis with raised ALT or fibrosis or cirrhosis
What is the important factor in determining treatment response in HBeAg positive chronic hepatitis
Elevation of ALT
Higher ALT more likely to respond
Duration of treatment for chronic hep b
HBeAg positive - continue for 12 months after seroconversion
HBeAg negative - lifelong once started because will relapse if xt stopped
Lifelong in compensated and decompensated
What is the most common cause of HCC worldwide
Hep b
What is the most common cause of HCC in Australia
Hep C (then etoh)
Who of those with hep b should be screened for HCC?
Family history of HCC Asian men over age 40 Asian women over age 50 African over age of 20 Over age of 40 with high HBV DNA and high ALT Cirrhosis
What is the recommended screening and freq for HCC
6 monthly AFP and ultrasound
What is post exposure prophylaxis for hep b
Vaccination
And hepatitis b immunoglobulin
What type of virus is hepatitis c
RNA flavivirus
What is the significance of genotypes in hep c
Different geographic distribution
- genotype 1+ 3 most common in Australia
Predicts response to treatment
Genotype 1 = poor response to interferon
Genotype 3 = poor response to DAA
Routes of transmission for hep c
Blood borne
IVDU
Pre-screening blood transfusions (pre 1990)
Tattoos
Vertical perinatal transmission (though less then HIV or hep b)
Sexual contact especially with co-existing sti and MSM with HIV
What is the presentation of acute hep c
70% have no symptoms
30% have mild jaundice, itch, fatigue
Acute hep c is the most unlikely to cause fulminant hepatitis
What blood tests and serology are seen in acute hep c
HCV RNA appears first followed by rise in transaminases then anti-HCV
There is an IgM and IgG form of anti-HCV but both are present I chronic and acute infection so do not aid diagnosis
What is the gold standard for diagnosis of acute hep c
Testing negative for anti-HCV immediately after exposure then re-testing 7-8 weeks after and having developed it
If this is not available then you can’t determine between flare of chronic or acute infection
How many acute hep c go on to chronic hep c without treatment
80%
20% clear the virus spontaneously - more likely if jaundiced and symptomatic
Treatment of acute hep c
Most will not present as are asymptomatic
In jaundiced patients presenting early can wait 12’weeks to see if spontaneous clearance occurs
In asymptomatic patients - treat with interferon for 24 weeks, causes an SVR in 60%
What is an SVR
Sustained virological response
- absence of HCV RNA 6 months after treatment or spontaneous treatment
Aim of treatment for hep
SVR = cure
What is the commonest cause of chronic viral hepatitis in developing countries
Hep b
What is the commonest cause of chronic viral hepatitis in western countries
Hep c
What is the commonest indication for liver transplant in western countries
Hep c
Predictors of chronic hep c infection developing from acute hep c
Age at acquisition - greater then 25 = higher risk Asymptomatic Co-infection with HIV Male African american Immunosuppression
Extra hepatic manifestations of hepatitis c
Mixed cryoglobulinaemia Lichen planus Type 2 diabetes Porphyria cutanea tarda (deposition of porphyns in skin which causes a photosensitive rash) Mebranoproliferative GN Lymphoma/splenic lymphoma Keratoconjunctivitis sicca
What do you need to be careful of in diagnosing an immunosuppressed patient with hep c
May get false negative anti-HCV test as they may never develop detectable levels of antibodies
What is difference about the anti-HCV compared to other hepatitis antibodies
It does not confer immunity to infection
Has no role in neutralising the virus
What are the indications to treat chronic hepaitits c
HCV RNA positive
Anti-HCV positive
Absence of contraindications to treatment
Predictors of response to treatment
IL28b gene (predicts better response to interferon and higher rates do spontaneous clearence)
Age less than 40
Female
Not obese
Genotype 2 and 3 (with interferon treatment)
Low viral load
No fibrosis/cirrhosis
RVR (rapid viral response - absence of HCV RNA after only 4 weeks of treatment)
List some options for treatment of hep c
Interferon + ribavirin high rates of side effects and SVR rates of only 20%
Peg-Interferon + ribavirin - SVR 40%
Peg-interferon + ribavirin + boceprevir or telepravir - SVR 60-70%
Interferon free regimes - sofosbuvir - SVR greater then 90%
What is sofosbuvir
NS5b RNA polymerase inhibitor
What are some side effects of ribavirin
Haemolytic anaemia Teterogenic Leukopenia Psychiatric side effects GI upset
Risk factors for progression of hep c complications (cirrhosis etc)
Histology (advanced fibrosis) Older age at infection Hep b or HIV co-infection Raised ALT Obesity or insulin resistance ETOH Male
What is the prognosis of hep c
5-10% will have cirrhosis at 20 years
Of those with cirrhosis per year
- 4-5% decompensated liver failure
- 1-3% HCC
- 3-4 % mortality
What is hepatitis D
A incomplete RNA delta virus which requires HBsAg to complete its replication inside a cell
Can only exist with hep b
What are the two types of hep d infection
Co-infection
- acute hep b and d occurring at the some time
Superinfection
- infection in someone with established chronic hep b
What is significant about hep d co-infection
Higher rates of severe hepatitis and fulminant hepatitis then acute hep b alone
Does not form chronic infection
What is clinically significant about hep d super-infection
Higher rates of progression to cirrhosis at earlier age
Fulminant hepatitis more common
Higher mortality rates
Usually presents as an exacerbation of chronic hep b
What is the serology for hep d
HDV ag and HDV RNA appear early
Followed by appearance of IgM anti-HDV
Not antibodies persist in the patient after infection, impossible to tell if someone has previously had infection
What is the mode of transmission of hep d
Same as hep b
- perisnatal
- horizontal transmission in childhood
- blood borne - IVDU
What is the treatment for hep d
Treat the hep b - hep d superinfection is an indication to treat hep b
What is hep e
A RNA calicivirus
What clinical picture does hep e produce
Self limiting illness almost identical to hep A
Who is the main population at risk in hep e
High mortality in pregnancy - 15% fulminant liver failure
25% mortality in 3rd trimester pregnancy
Where does hep e occur
Countries with poor sanitation as faecal oral transmission
Asia, Africa, India etc.
Occurs in the rainy seasons
