Response to interferon alfa is hepatitis B virus genotype dependent: genotype A is more sensitive to interferon than genotype D

Doubly Spliced RNA of Hepatitis B Virus Suppresses Viral Transcription via TATA-Binding Protein and Induces Stress Granule Assembly

“…Recent clinical studies have shown that patients infected with HBV genotype A or B, each of which transcribes 2.2DS-RNA, have less severe symptoms and liver pathology and higher rates of viral clearance in response to IFN-␣ therapy than patients infected with HBV genotype C or D, each of which is 2.2DS-RNA deficient (7,9,61,62). Our prior study found that relatively high levels of 2.2DS-RNAs were present in CHB patients with genotype A infection but not in those with genotype D infection (25).…”

“…Previous studies have shown that chronic hepatitis B patients infected with genotype A or B exhibit higher rates of seroclearance of HBV e antigen (HBeAg) and viral DNA in response to IFN-␣ therapy than patients with genotype C or D infection (7)(8)(9) and that chronically infected children with HBV genotype A infection have lower viral DNA loads and exhibit less severe symptoms than patients with genotype D infection (10,11). Clinical studies have also shown that differences between HBV genotypes correlate with deoxycytidine analog resistance (12) and hepatic pathogenesis (13).…”

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“…The success rate for Peg-IFNα treatment is highest in patients infected with genotype A and lowest in patients infected with genotype D (HBeAg seroconversion 46% and 24% respectively, HBsAg loss 13% and 2% respectively) (21,22). PegIFNα should not be given to patients who have normal ALT or HBV DNA of >10 9 IU/mL (22).…”

Current and future directions for treating hepatitis B virus infection

“…In a multicenter, randomized control trial conducted in Europe on peginterferon-alpha2a for HBeAg-negative patients comparing three groups treated with 48 wk of peginterferon-alpha-2a alone, 48 wk of peginterferon-alpha-2a plus lamivudine and 48 wk of lamivudine alone, the serum ALT normalization rates 24 wk after end of administration were 59%, 60% and 44% and the serum HBV DNA negative rates were 43%, 44% and 29%, respectively (Table 3) [33] . HBsAg converted to negative in 7 patients in the peginterferonalpha-2a alone group and 5 patients in the peginterferon- With respect to the factors affecting the outcome of interferon therapy, the HBV genotype [40][41][42] , age [43] and fibrosis of the liver [44] were reported to affect the therapeutic outcome of standard interferon. On the other hand, peginterferon is highly effective and the age and HBV genotypes are no longer related to the treatment effect of peginterferon except for HBV genotype A [45,46] .…”