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Flashcards in Hepatitis Deck (74):

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
- 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


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



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


What is the recommended screening and freq for HCC

6 monthly AFP and ultrasound


What is post exposure prophylaxis for hep b

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
Pre-screening blood transfusions (pre 1990)
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

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
Co-infection with HIV
African american


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
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
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


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

- acute hep b and d occurring at the some time

- 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