Comparison Between Genotypes I and II HDV

It hasbeenreportedthatgenotypeIIHDV infectionisrelativelylessfrequently associated with fulminant hepatitis at the acute stage and less unfavorable outcomes (cirrhosis or HCC) at the chronic stage as compared to genotype I of the same area [18]. This study was composed of symptomatic inpatients and asymptomatic outpatients for regular check up. In a longer follow-up for more than 15 years, about 45% of patients with chronic genotype I HDV infection survived, while more than 75% of patients with chronic genotype II HDV infection remained alive [63]. The difference is statistically significant. The long-term prognosis of patients with chronic genotype II HDV infection seems better than that reported previously in western countries where only genotype I HDV is currently found [10,11,17]. All the patients in the study by Ivaniushina et al. had a history of chronic liver disease, and all except two presented with grave liver disease or cirrhosis [26]. It is not surprising that there was no difference in the severity of infection between genotype I and II in this cross-sectional study of a selected group of patients. Moreover, the genotype II isolates from Yakutia clustered into a clade different from those from Taiwan and Japan (see the chapter by P. Deny, this volume); it is possible that the genotype II variant in Yakutia may be associated with different virological characteristics and clinical manifestations. In addition, different genotypes of HBV may also influence outcomes of patients with chronic hepatitis D. The impact of viral replication, mutations and genotypes of HBV on clinical manifestations were not analyzed in that study [26]. The influence of HBV will be further discussed in the following section. Genotype IIb (HDV-4 by Deny's classification) infection is not as common in Taiwan as in Okinawa [18, 19, 30-32]. It appears that the clinical manifestations and outcomes of patients with genotype IIb infection are more like those of patients with genotype II HDV infection in Taiwan (J.C. Wu, unpublished results) with relatively less unfavorable outcomes compared to genotype I [18, 19,30-32]. In the study by Watanabe et al. genotype IIb infection is associated with milder liver diseases as compared to the genotype IIb variant, type IIb-M, in patients of the same ethnic background living in Miyako [32]. Genetic variations in nucleotide and amino acid sequences of HDV may account for the heterogeneity in disease manifestations (Table 3).

Table 3 Comparison of virological and clinical behaviors between genotype I and II HDV

Genotype I

Genotype II

Distribution Worldwide

Genomicsize 1674-1679 nt

Oligomerization of HDAg No genotype-restriction

Transactivation by heterotypic small HDAg




Unfavorable outcomes Acute infection Chronic infection

Transactivated by both genotypes I and II

Comparable or higher Higher efficiency Higher efficiency More

More fulminant hepatitis More cirrhosis and HCC

Japan, Taiwan, Yakutia 1682-1685 nt No genotype-restriction Not significantly transactivated by genotype II Lower

Lower efficiency Lower efficiency Less

Fewer fulminant hepatitis Fewer cirrhosis and HCC

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