65,66 The therapeutic endpoints for chronic hepatitis B treatment include Wnt inhibitor sustained suppression of HBV replication to below the detection limit of real-time PCR assays, biochemical remission, histological improvement, HBeAg loss or HBeAg seroconversion for HBeAg-positive patients, and ideally HBsAg loss and HBsAg seroconversion.6–8 Currently, two types of therapy are recommended: standard or pegylated interferon alpha (IFN-α) and five nucleos(t)ide analogues, including lamivudine, telbivudine, entecavir, adefovir dipivoxil and tenofovir disoproxil fumarate.6–8 Although HBV genotyping before anti-viral therapy is not recommended by current guidelines from three regional liver associations,

the American Crizotinib Association for the Study of Liver Disease (AASLD),6 the European Association for the Study of Liver (EASL),8 and Asian Pacific Association for the study of liver (APASL),7 the impact of HBV genotype on therapeutic response to both interferon-based and nucleos(t)ide analogues has been increasingly recognized.67,68 In HBeAg-positive patients treated with standard IFN-α, the sustained response rate, defined as normalization of serum ALT level and HBeAg seroconversion post-treatment, is significantly

better in genotype A and B patients than for genotype C and D.51,69–71 For HBeAg-positive Asian populations, HBV genotype B patients are more susceptible to IFN-based therapy, regardless of pegylated or standard type IFN products, whereas genotype C patients have a higher likelihood of response to pegylated IFN-α

compared to standard IFN-α.72,73 Recently, Zhao et al. assessed the efficacy of low-dose, 24-week standard IFN-α or pegylated IFN-α treatment as well as factors predicting sustained response in Chinese patients with HBeAg-positive chronic hepatitis B.74 They found that HBV genotype B infection and younger 上海皓元医药股份有限公司 age were independent factors associated with sustained response, suggesting low-dose IFN regimen may be cost effective for the treatment of younger patients with genotype B infection. Another multi-center study on pegylated IFN-α for HBeAg-positive patients revealed that the rate of HBeAg clearance also differed according to HBV genotypes: genotype A, 47%; genotype B, 44%; genotype C, 28%; and genotype D, 25%.75 Subsequent analysis consistently demonstrated a higher rate of HBsAg clearance in genotype A compared to other genotypes in both HBeAg-positive and HBeAg-negative chronic hepatitis B.76 In addition, compared to genotype C and D patients, durable loss of HBeAg at 3 years after pegylated IFN-α treatment was higher in genotype A and B patients.77 Among HBeAg-negative patients treated with pegylated IFN-α, a long-term follow-up study also showed that HBsAg clearance was significantly higher in genotype A (20%) than genotype B (6%), genotype C (9%), and genotype D (6%).