Table 1: Virological and clinical comparison between HBV and WHV.

HBVWHV

Virology
ClassificationFamily: Hepadnaviridae Family: Hepadnaviridae
Genus: Orthohepadnavirus Genus: Orthohepadnavirus [91]
HostHumanWoodchuck (Marmota monax)
Structure40–42 nm spherical; enveloped nucleocapsid; partially double-stranded DNA genome [22]42–45 nm spherical; enveloped nucleocapsid; partially double-stranded DNA genome [91, 104]
ProteinsSurface glycoproteins (large-L, medium-M, small-S), core protein, “x” protein, “e” antigen, DNA polymerase with reverse-transcriptase activity [22, 105]The corresponding proteins [91]
Replication strategyReplication of HBV DNA occurs by reverse transcription of an RNA intermediate within cytoplasmic nucleocapsids [22]The same mechanism [97]
Genetic diversity8 major genotypes [105]1 major genotype (minor sequence differences) [91]
Integration into host chromosomeYes [22]Yes, often close to N-myc oncogene region [106]

Clinical course of infection
Epidemic350 million people infected worldwideEndemic in some woodchuck population in North America
Vertical transmissionThe most common: from mother to newbornNeonatal woodchucks infected by WHV inoculum
chronicity rate: 45%–90% [20, 105]chronicity rate: 60%–75% [92]
Horizontal transmissionTransmitted by body fluids, 90% of individuals recover [105]Adult woodchucks infected by WHV inoculum,
90%–95% of animals recover [92]
Clinical features of chronic infectionVariable HBV DNA levels:  copies/mLWHV DNA levels:  copies/mL
Variable HBsAg levelsWHsAg: mean 100–300 ug/mL
liver transaminases elevation [20, 22, 105]liver transaminases elevation [92, 107]

Disease progression
Liver cirrhosis2%–5% in HBeAg-positive patients (genotype dependent) [20]Not common
Hepatocellular carcinoma5-year cumulative HCC incidence in patients with cirrhosis: 16% (data in Asia) [20]Nearly 100% of chronic infected animals have HCC after 3 years [92, 94, 95, 107]
Efficacy of nucleos(t)ide analogues treatmentEffective: entecavir, tenofovir, telbivudine, adefovir, lamivudine [25]Effective: clevudine, telbivudine, entecavir, emtricitabine, tenofovir,
Less effective: tenofovir, adefovir, lamivudine [74, 108118]
Development of resistance mutationsYes [6, 7, 105]Lamivudine-resistant strains isolated [119]