HBV 2

Question 1

Patient with HBV awaiting liver transplant

What treatment is given before and after transplant?

Answer 1

• anti-viral drug e.g entecavir/ TDF/ TAF

- HBIG + anti-viral after transplantation to prevent recurrence - reduces risk to <5%

Question 2

Patient without HBV infection, receiving liver transplant from patient who is anti-HBc positive

Risk of reactivation after transplant

What are treatment options?

Answer 2

• HBsAg-negative patients receiving livers from donors with evidence of past HBV infection (anti-HBc positive) are at risk of HBV recurrence and should receive antiviral prophylaxis with a NA - lamivudine/ entecavir/ TDF/ TAF
• after transplant, patient will be on immunosuppression. So will be at lifelong risk of reactivation. Will need lifelong anti-virals

Question 3

HIV and HBV co-infected

What drugs should be included in the HIV ARV regime?

Answer 3

TDF/ TAF should be in regime

Question 4

HIV and HBV co-infected.

Has TDF/ TAF in regime. But now has bone/ renal disease

What are drug options?

Answer 4

Switch HIV ARVs to anything

Add entecavir, as HBV cover

Question 5

What is the importance of screening for HIV, in patients with confirmed HBV infection?

Answer 5

TDF/ TAF or entecavir monotherapy can cause HIV resistance mutations

Question 6

HBV and HDV co-infected patient

What are treatment options?

Answer 6

PegIFNa is only drug to show activity against HDV

• PegIFNa for at least 48 weeks is the current treatment of choice in HDV-HBV co-infected patients with compensated liver disease
• continue for 48 weeks if well tolerated. Do not stop even if HBV DNA levels are not responsive
• treatment success rates vary between 25-50%
• In HDV-HBV co-infected patients with ongoing HBV DNA replication, NA therapy should be considered

Question 7

HBV and HDV co-infected patient

Patient treatment with PegIFNa for 48 weeks

What further monitoring is required?

Answer 7

Continue to monitor HDV RNA levels, whilst patient is HBsAg positive

Loss of HBsAg represents cure of HDV infection.
However, only occurs in 10% of patients treated with PegIFNa. Some studies have trialled extending PegIFNa to 96 weeks, with minimal improvement

Question 8

HBV and HDV co-infection

You would presume that anti-virals may reduce HBsAg expression, and cure HDV infection. But this is not the case.

Why do antivirals entecavir/ TAF/TDF have no effect on HDV levels?

Answer 8

HDV if present, is the dominating virus.
Anti-virals have no effect on HDV RNA virus

However, if HBV DNA levels >2000, then anti-virals may have some effect, as suggests there is active HBV replciation

Question 9

HBV and HDV co-infection

Patient has decompensated liver disease

What are treatment options?

Answer 9

Peg-IFNa contra-indicated

Liver transplant is only option

anti-virals ent/TAF/TDF if HBV DNA detectable

Question 10

HBV and HCV co-infection

Patient starting HCV DAAs

Does not currently fit criteria for HBV treatment

What are things to consider?

Answer 10

HCV treatment can result in HBV reactivation, as HBV then becomes the dominant virus

HBsAg pos patient - give ent/TAF/TDF until 12 weeks post DAA therapy

HBsAg neg patient - monitor ALT. If rises check HBV DNA and consider ent/TAF/TDF

Question 11

Patient with acute HBV infection

What are treatment options

Answer 11

More than 95% of adults with acute HBV hepatitis do not require specific treatment, because they will fully recover spontaneously (conversion to anti-HBs)

Only patients with severe acute hepatitis B, characterised by coagulopathy or protracted course, should be treated with NA and considered for liver transplantation

Question 12

Child with chronic HBV infection

What are treatment options?

Answer 12

Most are asymptomatic, or have mild infection

ent/ lam/ TDF/ TAF are all safe in children aged 12-18.
and likely safe in younger children

Question 13

HBV in pregnancy

Which drugs are safe/ suitable during pregnancy?

Answer 13

TDF

TAF - likely safe, but more data needed
Entecavir - recommend switch to TDF
Lamivudine - recommend switch to TDF
PegIFNa - contra-indicated

Question 14

What are recommendations for breast feeding in pregnant patients who are HBsAg positive?

Answer 14

Acceptable if not on treatment - HBsAg detectable in breast milk, although minimal risk of infection

Acceptable if on treatment - TDF is safe for breast feeding

Question 15

Pregnant female HBsAg positive

Plan to give baby HBIG and vaccine

Mother has high HBV viral load 200 000, and you consider prophylaxis to reduce risk of transmission

Which drug would you start, and when?

Answer 15

In all pregnant women with high HBV DNA levels ([200,000 IU/ml) or HBsAg levels [4 log10 IU/ml antiviral prophylaxis with
TDF should start at week 24–28 of gestation and continue for up to 12 weeks after delivery

duration after delivery does not have strong evidence

Question 16

Patient with HBV infection, and extra-hepatic manifestations

Which drugs can be used?

Answer 16

PegIFNa contra-indicated - as would further stimualte immune response

ETV/ TDF/TAF

Question 17

which HBV markers may be useful in the future?

Answer 17

cccDNA

HBV RNA

HBV core-related antigen

Question 18

Why is it difficult to “cure” HBV infection?

Answer 18

HBV DNA integrates into genome - can produce HBsAg, but cannot produce full virion

cccDNA remains in nucleus, and acts as template for viral replication

Question 19

Renal patients require immunisation with 3x doses HBV vaccine

When are blood tests checked for immunity?

Answer 19

Check anti-HBs 8 weeks after last immunisation

Question 20

Renal patient has been immunised with 3x doses HBV

Check anti-HBs at 8 weeks

What action would you take with the following results?

> 100 IU/ml

10-100 IU/ml

<10 IU/ml

Answer 20

> 100 IU/ml - responder. Receive annual booster, if annual anti-HBs check is <100 IU/ml

10-100 IU/ml - inadequate responder. Administer booster, and re-check in 4 weeks

<10 IU/ml =- non-responder. Repeat the entire vaccination course. Follow up with an anti-HBs antibody titre test 4 to 6 weeks following the last injection to
ensure it is greater than 10m IU/l

Question 21

Renal patient has had HBV immunisation
Was a non-responder with anti-HBs <10

So completed a second immunisation course

What should be done if patient still fails to respond?

Answer 21

If after two full vaccination courses the Anti HBs titre remains <10mIU/ml the patient should be considered as a non-responder to the vaccine, and therefore not
immune to HBV.

A non-responder patient, who is therefore not immune to HBV, should be counselled about how to minimize risk of HBV exposure and the recommended actions needed to take in the advent of a potential Hepatitis B exposure (this is likely to include urgent receipt of Hepatitis B immunoglobulin)

Question 22

Renal patient who has been immunised against HBV

What annual follow up is required?

Answer 22

Annual anti-HBs - if level drops <100 IU/ml - give booster dose

If known non-responder - check HBsAg annually

If previously a responder, then drop anti-HBs to <10IU/ml, which does not increase with booster - then consider non-responder. Check HBsAg annually

Question 22

Renal patient who has been immunised against HBV

What annual follow up is required?

Answer 22

Annual anti-HBs - if level drops <100 IU/ml - give booster dose

If known non-responder - check HBsAg annually

If previously a responder, then drop anti-HBs to <10IU/ml, which does not increase with booster - then consider non-responder. Check HBsAg annually

Question 23

Renal dialysis patient has been previously a HBV vaccine responder

Wishes to travel overases

What checks are required?

Answer 23

Check anti-HBs and boost if <100 IU/ml

Question 24

What are new classes of drugs that can be used to treat HBV in the future?

Answer 24

Entry inhibitors

Translation inhibitors

Capsid assembly inhibitors

HBsAg secretion inhibitors

Innate immunity activators

Adaptive immunity activators