38 Furthermore, the association of HBsAg reductions with sustained responses was observed across the major genotypes (A-D).40 Although these low on-treatment levels were reached by less than 25% of the treated patients, these encouraging data suggest a potential role for HBsAg levels in predicting the response to PEG-IFN. This

could encourage or motivate patients to complete their course of therapy. The ability to determine who is most unlikely to achieve a sustained response to PEG-IFN might be of more practical value for patient management. The early identification of nonresponders would allow the discontinuation of therapy and/or changes in the treatment strategy for these patients. High negative predictive values (NPVs) for response have been reported for this website both HBeAg-positive and HBeAg-negative patients. Sonneveld et al.26 reported an NPV of 97% for 202 PEG-IFNα2b–treated, HBeAg-positive patients (74% with genotype A or D HBV), which was based on any decline in HBsAg levels at week 12. An HBsAg decline at week 12 had an NPV of 82% in another large study of PEG-IFNα2a therapy (88% with genotype B or C HBV).41 The Hong Kong study reported an NPV of 86% for HBsAg levels < 1500 IU/mL at month 3 and an NPV of 89% for levels <

300 IU/mL at month 6.35 The Chinese study also showed that an Sotrastaurin HBsAg level < 1500 IU/mL at week 12 had an NPV of 91%, whereas the NPV was 95% when the cutoff level was 2890 IU/mL at week 24.36 For HBeAg-negative patients, Moucari et al.38 reported Sclareol an NPV of 90% for an HBsAg decline of 0.5 log10 IU/mL at week 12 and an NPV of 97% for a decline of 1 log10 IU/mL at week 24 in a mixed-genotype population. In a population that mainly

had genotype D, Rijckborst et al.39 reported an NPV of 100%, which was based on a combination of an HBsAg decline and a 2 log10 IU/mL decline in HBV DNA levels from the baseline to week 12. This proposed stopping rule was recently validated in another cohort of patients treated with PEG-IFN.42 These apparently robust early stopping rules with high NPVs could help with the management of patients and may even encourage patients to consider PEG-IFN as first-line therapy. This may be particularly applicable when the alternative is most likely lifelong therapy with NAs, especially for patients with HBeAg-negative disease. On the basis of these studies in different populations with different genotypes, week 12 of IFN-based therapy seems to be the right time for assessing an HBsAg decline (Table 4). However, the most appropriate degree of this decline still needs to be established before it can be adopted by the community as a guide for clinical practice. HBsAg profiles were also analyzed retrospectively in hepatitis C virus (HCV)/HBV-coinfected individuals treated with PEG-IFN and ribavirin for their predominant HCV infection.