Hepatitis D

Question 1

HDV structure and classification

Answer 1

Defective virus with life cycle dependent on HBV - borrows all 3 envelope proteins (HBsAg) to enter and egress from hepatocytes.

Kolmioviridae family
Deltavirus genus

(-)ssRNA

Baltimore: V

Question 2

HDV receptor & replication

Answer 2

Does NOT have its own RdRP or RdDP.

Uses host RNA polymerase II to replicate by rolling circle RNA synthesis (like TTV).

Uses HBsAg to form its envelope.

Encodes a single structural protein HDAg expressed in 2 isoforms:

Small protein S-HDAg for viral replication
Large protein L-HDAg for packaging of mature curious

The 2 proteins bind to the HDV RNA to form a ribonucleoprotein surrounded by an envelope containing all 3 HBsAg isoforms.

HDV binds to the same cell receptor as HBV - sodium taurocholate cotransporting polypeptide (NTCP).

Question 3

Antivirals for HDV

Answer 3

Buleviritide & Lonafarnib in phase III trials

Buleviritide- blocks binding of HBsAg to NTCP

Lonafarnib - inhibits the prenylation step of HDV replication inside liver cells and blocks the virus life cycle at the stage of assembly - D-LVER trial

Question 4

HDV screening indications

Answer 4

1. All HBsAg positive patients with a validated assay for anti-HDV Abs
2. Re-testing when clinically indicated/yearly when ongoing infection risk

Question 5

HDV diagnosis confirmation

Answer 5

Validated HDV RNA RT-PCR in all patients with a positive anti-HDV Ab

Question 6

HBV/HDV confection vs superinfection testing

Answer 6

Co-infection: Anti-HBc IgM + Anti-HDV IgM positive

Superinfection - acute HBV markers absent

Question 7

Chronic HDV treatment

Answer 7

Chronic HDV + compensated liver disease:

48 weeks PEG IF alpha followed by HDV PCR testing at 6 & 12 months post treatment

OR

Buleviritide 2mg OD long term - duration not specified - test HDV every 6 months whilst on treatment

OR

Combination IF + BLV

Question 8

Buleviritide

Answer 8

Synthetic lipopeptide of the pre-S1 region of HBsAg - blocks attachment of HBsAg to cell entry receptor NTCP for both HBV & HDV.

Studies showed significant reduction of HDV but NOT HBV.

DO NOT USE IN DCLD - Caveated with the recent lancet paper showing similar efficacy and ADRs in delta patients with DCLD.

Question 9

Chronic HDV + decompensated CLD

Answer 9

1. Nucleotide analogues irrespective of VL
2. Nucleotides given without CLD aid HBV levels > 2000 in HDV co-infection

Off-label buleviritide showed comparable efficacy as in compensated CLD in 19 patients in European study 2024.

Question 10

HDV prophylaxis after liver transplant

Answer 10

HBIG + nucleotide analogue indefinitely

HBIG to maintain anti-HBs levels >100 mIU/ml