[108, 109] However in the absence of a broad consensus on this at the present point in time, there cannot be said to be sufficient evidence for improved therapeutic effects of IFN administered in combination with NAs. Recommendation There

is insufficient evidence for improved therapeutic effects of IFN administered in combination with NAs. Factors reported to determine the therapeutic effect of conventional IFN include HBV genotype,[104, 110, 111] age,[112] and Vemurafenib cell line the degree of fibrosis.[113] However, as shown below, Peg-IFN has a high therapeutic effect compared to conventional IFN, and has high efficacy against HBV genotype A, but its therapeutic effect is not influenced by other HBV genotypes or patient age. Currently, regardless of whether a patient is HBeAg positive or negative, there is no established method for predicting the treatment response prior to Peg-IFN treatment, with the exception of HBV genotype A (Tables 12, 13). α-2a 180 μg α-2b 100 μg α-2a: 48 weeks α-2b: 52 weeks Concerning correlations between genotype and therapeutic effect, for conventional IFN therapeutic effect is reported Sirolimus manufacturer to be high for genotypes A and B compared to genotypes C and D.[104, 110, 111] For treatment using the minimum dosage (90 μg)

of Peg-IFNα-2a or short period (24 weeks), poorer therapeutic response has also been reported for genotypes C compared to genotype B.[98] However, the recent NEPTUNE study evaluated the therapeutic effect of Peg-IFNα-2a 180 μg/48 weeks, finding the response rate of antiviral therapy was the same for genotypes

B and C, and genotype was not a predictive factor for therapeutic effect.[10] Possible reasons for this are that due to increased therapeutic effect from administration of Peg-IFNα-2a 180 μg for 48 weeks, any influence on the therapeutic effect from genotype C was lost. The results of other large scale clinical trials for HBeAg positive cases indicated strong Peg-IFN therapeutic effect for genotype A compared to genotype D,[114, 115] but no difference in therapeutic effect between genotype B and genotype C was find more seen[8] (Table 12). In HBeAg negative cases also, no significant difference in response rate was found between genotype B and genotype C[23, 117-119] (Table 13). In recent years highly sensitive measurement of HBsAg levels has become possible, and it has been noted that HBsAg levels are useful in predicting IFN therapeutic effect. Although it is difficult to predict the therapeutic effect from the pretreatment HBsAg levels, the amount and rate of reduction in HBsAg levels during treatment are useful in predicting therapeutic effect.