Viral hepatitis RPA Flashcards
Who is at risk of hep C?
IVDU Migrants from high prevalence areas - egypt, pakistan, miditerranean, eastern europe, africa, asia ATSI - mother to baby Sex workers Other blood bourne viruses Children with positive mothers needle stick injury
Risk of acute hep C progressing to chronic hep C
75% will go to HCV
Another 30% will progress to liver cancer, liver failure, cirrhosis
Risk Factors associated with increased rate of progression to cirrhosis in HCV
Metabolic risk factors especially
Diabetes, obesity, MAFLD, ETOH, genetic factors, post-menopause in women, age at infection, HCV genotype 3, HIV co-infective
Even if HCV is treated, can still develop cirrhosis later on. Will require ongoing monitoring after HCV treatment if above risk factors present.
How do we assess fibrosis?
1)
APRI score (AST platelet ratio index)
<1: unlikely to have fibrosis. Can be DC from follow up if HCV is treated and no risk factors i.e. metabolic risk factors
Also Hepascore
<0.8: unlikely
Others
Fibrogene (not used much at the moment)
2) Fibroscan (transient elastography)
- More specific than APRI but equally sensitive
- High NPV
- Cirrhosis likely if MLS ≥12.5
- Unlikely if MLS <12.5
How do we assess fibrosis?
1)
APRI score (AST platelet ratio index)
<1: unlikely to have fibrosis. Can be DC from follow up if HCV is treated and no risk factors i.e. metabolic risk factors
Also Hepascore
<0.8: unlikely
Others
Fibrogene (not used much at the moment)
2) Fibroscan (transient elastography)
- More specific than APRI but equally sensitive
- High NPV
- Cirrhosis likely if MLS ≥12.5
- Unlikely if MLS <12.5
Benefits of HCV cure
12 weeks after treatment can impede fibrosis progression, can reverse liver decompensation, prevent liver decompensated, reduce risk of HCC and transplant
Reduce mortality
Reduce extrahepatic complications
- Reduce liver associated NHL, CV disease, renal disease, neurocognitive dysfunction, improve QOL
Reduces HCV transmission
DAA treatment for HCV
Standard treatment
- All oral treatments
- 98-100% efficacy in both fibrosis and non-fibrosis
- All pan-genotypic
SOF-VEL (epclusa)
- 12 weeks
GLE-PIB (Maviret)
- 8 weeks
Resistant treatment SOF-VEL-VOX (vosevi) - Salvage regimen - high effective for those who have failed standard therapy due to resistance - Has protease inhibitor
Does HIV coinfection, actively drinking ETOH, reinfection of HCV, cirrhosis reduce the chance of cure?
No
Nothing reduces the risk of cure
Challenges with DAA treatments
Drug drug interactions (PPI reduce absorption of DAA, statins can cause rhabdo, OCP, amiodarone can cause CHB)
Protease inhibitors are CI in decompensated cirrhosis
Accurate pre-treatment assessment of fibrosis status so that cirrhotic patients get appropriate regimen and duration, and are enrolled in long-term follow up with liver ca surveillance regatrdless of SVR
Can you use DAAs in dialysis/CKD?
yes
Can you use DAAs in children >12 years
yes
can you use DAAs in preganncy?
No
Small risk of mother to baby transmission (2-5%)
Can you get reinfected post HCV curte?
Yes
There is no immunity to HCV
Need to do RNA test to check reinfection (can’t do antibody)
Resistance is almost always towards …
NS5A inhibitors and protease inhibitor
WE don’t check for these
HCV and HBV coinfection
How should we manage this?
HBV DNA is low or undetectable
HCV is usually driver of hepatic inflammation
Potential risk of HBV reactivation after/during HCV clearance with DAA therapy
Hep B should be checked before DAA treatment and be treated at the same time
HCV and COVID19 is it worse?
No increased mortality or ICU admission
Cirrhosis and COVID19 is it worse?
Increased mortality from lung disease and decompensated liver disease
Mother to baby transmission
How likely is this?
Mother to baby
- If baby doesn’t receive prophylaxis, 95% of chronic HBV infection
Should we check HBV genotype?
No
However
Asia - B (less active disease, low HCC, less progression), C (high HCC, cirrhosis)
A and B respond better to IFN than C and D
F is fulminant disease but rare
How
Mother to mother
IVDU
MSM
When to check hep B?
At risk populations e.g. SE asians, africa, middle east IVDU MSM Pregnant women Before immunosuppression/chemotherapy
Factors associated with increased risk of cirrhosis and HCC in hep B?
Persistent high HBV DNA or presence of HBeAg
HBV phenotype C>B
Core promotor mutations
Coinfection with HCV, HDV, HIV
Male Metabolic risk factors FHx HCC Cirrhosis Heavy ETOH
Models for prediction of HCC in HBV
REACH-B
Age, gender, HBV DNA< ALT, HBeAg
Tests to do in confirmed Hep B
HBeAg
Anti-HBe
HBV DNA
ALT
Fibrosis assessment
4 phases of hep B
1) Immune tolerance
- Positive HBeAg
- high HBV DNA
- Low ALT
2) Immune clearance
- ALT flare
- HBV DNA drop
- At some point, seroconvert from HBeAg to Anti-HBe (ab)
3) Immune control
- Low HBV DNA
- Low ALT
- Anti-HBe (ab) positive
4) Immune escape
- High ALT and HBV DNA
- Low anti-HBe (ab)
Which phase do we treat hep B?
we target therapy in immune clearance and immune escape
However, no such thing as a healthy carrier. We need to monitor annually no matter what phase they are in.
Can we cure hep B?
No
We just suppress it
Treatment of chronic hep B
Entecavir - preferred; no effect on bone or kidney Tenofovir disaporxil (TDF) - associated with bone and kidney dysfunction Tenofovir alafenamide (TAF) - TGA approved but not PBS reimbursed. Less toxicity compared to TDF.
When to treat hep B?
ALT >2 ULN
HBV DNA elevated
Can we stop hep B treatment?
Can stop after HBeAg negative but significant risk of relapse
Risk of HBV in chemotherapy patients
Can be fatal
Reactivation can result in elevated liver enzymes, jaundice, acute hepatic failure and death
Can occur up to 2/3 of HBsAg positive patients undergoing chemotherapy especially B cell depleting therapies (in lymphoma/leukemia, RA)
Can also occur in anyone under immunosuppression in solid tumours, rheumatology, IBD, transplant settings
Babies born to mothers who are HBsAg positive are given …
HBIG and HB Vax x3
Pregnant women on antiviral therapy for Hep B
Can stop or continue tenofovir
How to get hep D hepatitis?
How to treat it?
Need hep B surface antigen to replicate
Nucleoside and nucleotide therapy not impact hep D viraemia or outcomes
Only rx available is Peg-interferon - 25% response rate only
Bulevirtide - inhibitor of HbsAg entry via binding to the NTCP receptor hepatocytes - approved in europe
Hep E
RNA virus
Small
Found in humans, pigs, cows, rodents, deer, moose, camels, boars
Transmission of hep E
Can be food acquired - pork in Europe
Most outbreaks associated with faecally contaminated drinking water (Subcontinent north africa, asia, russia)
Can also be transmitted through blood
Hep E and pregnancy
High rates of acute liver failure and death
genotypes 1 and 2
CAn you get chronic hep E?
Not in immunocompetent
Only in immunocompromised especially HEV infected organ transplants
Diagnosis Hep E infection
Detection of anti-HEV antibodies
Rx acute hep E infection
No treatment required. Infection will just clear.
But in immunosuppression, may not clear and will need ribavirin. However can get treatment failure associated with resistance.
Vaccine hep E?
Yes
100% efficacy after 3 doses
But only licensed in China and not accessible to the rest of the world
Most common cause of acute hepatitis?
Hep E
Cirrhosis and chronic hep B
How long to treat?
Treat indefinitely with tenofivir or entecovir even if low viral load
Which agent is safe in pregnancy?
Tenofivir
