HB eAg‐negative chronic hepatitis B: why do I treat my patients with pegylated interferon‐alfa?

HB eAg‐negative chronic hepatitis B ( CHB ) is the most frequent and aggressive type of CHB . The current therapeutic options for CHB include pegylated‐interferon‐alfa ( PEG ‐ IFN α) and nucleos(t)ide analogues ( NA s). NA s are well‐tolerated and safe agents that effectively inhibit viral replication, but they should be given as long‐term, probably lifelong therapy, in particular in HB eAg‐negative CHB . Thus, the finite, usually 48‐week, duration is the main advantage of PEG ‐ IFN α, providing sustained virological responses ( SVR ) off‐therapy in approximately one‐fourth of patients with HB eAg‐negative CHB and often leading to HB sAg loss. However, the limited efficacy is the main factor restricting the use of PEG ‐ IFN α in CHB and therefore identifying the predictors of response is of great clinical importance. No reliable baseline predictors of response to PEG ‐ IFN α have been identified to date, but certain studies have identified satisfactory predictors of post‐ PEG ‐ IFN α response using on‐treatment serological markers, mostly HB sAg levels. In particular, in HB eAg‐negative CHB patients mostly with genotype D a lack of decline in HB sAg levels and a lack of decrease in HBV DNA levels ≥2 log 10 copies/ml at week‐12 has a nearly 100% negative predictive value for SVR off‐treatment and is now recommended as a stopping rule for early discontinuation of ineffective PEG ‐ IFN α. Prolonging PEG ‐ IFN α therapy to 96 weeks seems to provide higher SVR rates but the application and efficacy of this approach requires further study. The combination of PEG ‐ IFN α with NA s, mostly lamivudine, has not resulted in any therapeutic benefit so far, but newer combined approaches with PEG ‐ IFN α and NA (s) are currently under study.