Can Nucleos(t)ide Analogue (NA) Therapy Ever be Stopped in HBeAg-Negative Chronic Hepatitis B?

In this review, evidence is presented that the majority of HBeAg-negative CHB patients previously treated with lamivudine and subsequently with adefovir and entecavir, experience virological and clinical relapse if these therapies were discontinued. Thus current treatment guidelines both of AASLD and EASL recommend indefinite duration of NA treatment in such patients. However, the recommendations of APASL are different, advising a stop of NA treatment if HBV-DNA is negative in three consecutive assays at least 6 months apart. It is clear that the duration of post-treatment sustained remission is variable and its final outcome unpredictable. However, fluctuations of post-treatment HBV-DNA levels are not uncommon and HBeAg-negative CHB patients may experience long periods of transient HBV-DNA undetectability. Data on the frequency of post-treatment HBsAg loss are promising but still limited. The need for prospective, multinational, multicenter studies is stressed.