Table 1.

Pros and cons of the different HDV in vivo models.

Model	Pros	Cons	Ref.
Chimpanzees	Full HDV life cycle, innate and adaptive immune system, HBV infection	Highly restricted availability, ethical concerns and high costs	[15,44,45,46]
Woodchucks	Full HDV life cycle, innate and adaptive immune system	Co-infection only with woodchuck hepatitis virus (WHV), limited availability, high costs and difficulties in the experimental performance	[50,51,52,53,54,55,56,57]
Hydrodynamic mouse models	Innate and adaptive immune system	No HDV entry, HDV clearance within 30 days, liver damage due to large injection volume	[68,69]
Human liver chimeric mice	Full HDV life cycle, innate immune system, HBV infection, life-long HDV persistence	No adaptive immune system, limited availability, high costs	[75,81,82,83,84,85,86]
AAV based mouse models	Innate and adaptive immune system, liver inflammation and damage, HBV replication	No HDV entry, HDV decline after 21 days until 45 days (long-term data missing)	[96,97]
hNTCP transgenic mice hNTCP/BAC mice	Innate and adaptive immune system	Low HDV infection efficacy, HDV clearance within 21 days, no HBV infection, presence of mNTCP	[101,105]
Mice with humanized NTCP (CRISPR/Cas, TALENs)	Innate and adaptive immune system	Low HDV infection efficacy, HDV clearance within 21 days, no HBV infection	[98,106]