Smedile et al. reported that HBV replication modulates pathogenesis of HDV in chronic hepatitis D . Wu et al. also reported that persistent replication of HBV or HDV are associated with elevated serum transaminase levels . Based on an intergroup divergence of 8% or more in the complete nucleotide sequence, HBV can be classified into eight genotypes A-H . Genotypes andcorepromotermutations ofHBVhavebeenreportedtobeassociatedwith time of HBeAg seroconversion, HBV DNA levels, treatment response to interferon and long-term outcomes [47-62]. Because chronic hepatitis D patients still have underlying chronic hepatitis B, replication status, genotypes and mutations of HBV may also influence clinical course and outcomes of chronic HDV infection. In a recent study in our laboratory, persistent replication of HBV or HDV was associated with higher adverse outcomes (cirrhosis, HCC or mortality) compared to those who cleared both viruses from sera . HBV genotype C is also a significant factor associated with adverse outcomes (cirrhosis, HCC or mortality) in patients with chronic hepatitis D, in addition to genotype I HDV and age. However, most of patients with chronic HDV infection have low or undetectable HBV DNA levels [12, 14]. During longitudinal follow-up, genotype I HDV is the most important determinant associated with survival.
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