Viral Hepatitis Flashcards
1
Q
Virology of Hepatitis C
A
- RNA virus
- Copying errors during replication → viral diversity → no vaccine, allows virus to escape host’s immune system
- Seven genotypes
- Genotype 1 most common in the US and Europe
- Genotype 3 most common in Australia, most difficult to treat with direct acting antivirals
2
Q
Examples of extra-hepatic manifestations of Hepatitis C infection
A
- Membrano-proliferative GN
- Porphyria cutanea tarda
- Cryroglobulinaemia
- Rheumatological - arthralgias
- Sjogren’s
Hepatic complications
- Cirrhosis
- HCC
3
Q
Natural history of Hepatitis C infection e.g. outcomes
A
4
Q
Risk factors for Hepatitis C infection
A
- IVDU (inc. ever IVDU)
- Aboriginal & Torres Strait Islanders
- Migrants from high prevalence countries (Egypt, Pakistan, Mediterranean and Eastern Europe, Africa, Asia)
- People in custodial settings (prisons)
- Sex workers
- Tattoos/body piercings
- People who received blood products/organ transplant before 1990
- Babies born to HCV infected mothers (risk <1%)
- Sexual partners of HCV infected persons
- People infected with HIV or Hepatitis B
- People with evidence of liver disease
- Needlestick injury
5
Q
How to diagnose Hepatitis C
A
- Hepatitis C antibody (indicates prior exposure) - if positive test HCV RNA (indicates current infection)
- Can get false negative antibody tests in severely immunocompromised - should do HCV RNA anyway
- If +ve antibody and no RNA BUT ongoing risk → test yearly for HCV RNA
Other investigations
- HCV genotype
- HIV, Hepatitis A & B serology
- U&Es, LFTs, CBC, INR
- Evaluate for cirrhosis - ultrasound and AFP if concerns re cirrhosis
- Notify regional public health
6
Q
Methods for assessing for liver cirrhosis:
A
- Clinical features - ascites, jaundice, spider naevi
- Ultrasound features of cirrhosis or portal hypertension
- APRI score - only need AST and platelet count
- Very high negative predictive value - any score <1 unlikely to be cirrhosis
- Fibroscan → assess the “stiffness” of the liver
7
Q
Principles of treatment Hepatitis C and classes of drugs used
A
- All people living with HCV should be treated
- 8-12 weeks combination therapy with duration of treatment 8-12 weeks
- Goal is sustained virological response (SVR) defined as pCR negative 12 weeks after completion date of hepatitis C therapy
Classes of drugs
- NS3 /4a protease inhibitors (can’t be used in decompensated cirrhosis)
- NS5A inhibitors
- Nucleoside polymerase inhibitors
- Non-nucleoside polymerase inhibitors
- Ribavarin
8
Q
Potential drug interactions with DAAs for Hepatitis C
A
- PPIs - reduce effectiveness, should stop or dose reduce (or dose at different time of day to Hep C therapy)
- Higher dose statins → rhabdomyolysis
- Amiodarone - can precipitate heart block
- Anti-epileptics - note cytochrome P450 interactions
9
Q
Notes on resistance-associated substitutions in Hepatitis C
A
- Most clinically significant is T93H - associated with decreased response to common DAA regiments
- Vosevi regimen effective in many with resistant mutations
10
Q
Notes on hepatitis C with decompensated cirrhosis
A
- Require specialist assessment
- Genotype 3 cirrhotics - most challenging population to treat
- Protease inhibitors relatively contraindicated
- Risk of liver failure
- Consider transplant referral.
11
Q
Non-pharmacological principles of Hepatitis C management
A
- Address IVDU if present
- Counsel re transmission risk
- Avoid factors that accelerate liver disease → avoid alcohol, weight loss if obese, cessation of cigarette and marijauna smoking
- 2-3 cups of coffee a day apparently reduced risk of hospitalisation & mortality in CLDs (inc. chronic viral hepatitis, alcoholic liver disease and NASH)
- Dose adjust medications e.g. 2g paracetamol/day if liver disease, avoid NSAIDs, statins probable ok
- Vaccination → hepatitis A and B if not immune, pneumococcal vaccine if CLD
- Monitor for cirrhosis: If cirrhosis present → needs monitoring for varices and 6 monthly ultrasound for HCC
12
Q
Significance of Hepatitis C treatment and hepatitis B infection:
A
- Risk of hepatitis B reactivation during treatment for Hep C
- Hep BsAg positive - check PCR at baseline and treat if meet criteria
- Hep B cAb positive: check LFTs week 4-8 and test PCR if increase
13
Q
Notes on vertical transmission of Hepatitis C infection:
A
- Risk if 5% in HCV monoinfected women, 10% if HIV co-inection
- Risk factors for vertical transmission:
- High HCV viral load
- IVDU
- Prolonged rupture of membranes and obstetrics procedures
- Factors not associated with vertical transmission:
- Viral genotype
- Mode of delivery (have have vaginal delivery)
- Breastfeeding → viral RNA passed in breast milk but no disease transmission
- Note DAA safety not assessed in pregnancy → women should be counselled to avoid pregnancy prior to starting DAA therapy
- Testing for HCV antibodies immediately after birth can lead to false positive → test at 15-18 months
14
Q
At risk individuals who should be tested for Hepatitis B
A
- People born in Asia, Africa, Middle East, Pacific Islanders Eastern and Southern Europe
- Aboriginal and Torres Strait Islanders
- Maori
- Pregnant women
- MSM
- Sex workers
- Haemodialysis patients
- IVDU
- People with another STI, hepatitis C or HIV
- Sexual, household contacts and family members of a positive case
- Everyone prior to receiving immunosuppressive therapy or chemotherapy
- People with elevated ALT/AST of unknown aetiology
15
Q
Transmission of HBV infection
A
- Vertical/perinatal → most common
- HBeAg +/- high HBV viral load → increases risk of vaginal transmission
- No protective effect C section, breast feeding does not increase risk
- Horizontal → skin, mucosal breaks, schoolchildren
- Sexually acquired
- Percutaneous → IVDU, tattoos, acupuncture, body piercing, household inc. toothbrush, razors
- Blood transfusion/medically acquired/nosocomial
- Surgery, dentistry, dialysis, finger pricks
16
Q
Notes on Hepatitis B disease progression
A
- Can cause HCC without cirrhosis
17
Q
Notes on HBV structure
A
- DNA virus - incoorporated into genome - not currently curable
- Partially double stranded
- Surrounded by nucleocapsis = core antigen
- Positive core antigen = exposure to Hepatitis B
- Surrounded by envelope - Hepatitis B surface antigen
- E antigen = surface antigen = highly infectious
18
Q
Tests to order when hepatitis B suspected
A
- Generally don’t routinely order genotypes
- A& B → better response to pegylated interferon
- C & D → generally more severe disease and more likely to progress to cirrhosis
19
Q
Interpreting results of Hepatitis B tests
A
HbsAg negative, anti-HBc positive, anti-HBs negative
- Distant quiescent HBV infection → most common scenario, especially in people born in HBV endemic areas
- False positive result
- Resolving acute HBV infection
- Occult HBV infection
If HepB sAg positive → refer to speciality clinic → HBV DNA and markers of liver disease
If Hep B cAb positive → risk of reactivation with immunosuppression
If all negative immunise
23
Q
Phases of Hepatitis B
A
24
Q
Management of HbeAg positive patients
A
25
Q
Management of HbeAg negative patients
A
26
Q
Monitoring in Hepatitis B and frequency
A
28
Q
Treatment options for Hepatitis B
A
First line oral antivirals
- Entecavir → possible increased risk lactic acidosis. Avoid if previously developed resistance to lamivudine.
- Tenofovir fumarate (TDF) → renal toxicity, bone mineral density loss
- Tenofovir alafenamide (not on PBS)
- Generally held to be equivalent
50-75% reduction in HCC risk over 5 years
- Cost effective cancer prevention intervention
- Virological suppression common. HBsAg seroconversion rare.
- Indefinite treatment. Adherence important
29
Q
Pegylated interferon vs oral antivirals in hepatitis B
A
