HBeAg-positive patients
The end points of treatment are not clearly defined and differ in HBeAgpositive versus negative disease. Ideally, patients will clear HBsAg by developing anti-HBs. This is, however, relatively infrequently achieved.
Although it is reasonable to infer improvement in liver disease if HBV replication is suppressed with an accompanying improvement in serum ALT, the absolute or relative decreases in serum ALT and HBV DNA that will alter the disease outcome have yet to be categorically defined.
HBeAg-positive disease
The most potent antivirals with the highest barrier to resistance, in particular tenofovir or entecavir are recommended. Patients may also respond to pegylated interferon.
Currently, antiviral therapy for HBeAg-positive disease is directed to attaining loss of HBeAg and, ideally, durable seroconversion to anti-HBe. This represents the transition from chronic hepatitis B to the inactive HBsAg state. A proportion of patients may go on to lose HBsAg.
Although this is a potential stopping point, treatment with nucleoside analogues should be prolonged for six months to one year after loss of the HBeAg. The durability of this response requires assessment in the future.
Finite courses of treatment are possible in only a minority of HBeAg positive patients and the majority still require longterm maintenance suppressive therapy.
Ideally profound and rapid reductions in HBV DNA are critical for longterm therapy, to reduce the risk of development of resistance to antiviral therapies. Loss of HBsAg, in the setting of low HBV DNA levels is the ideal end point but is attained in only a minority.
Anti-HBe positive disease
For patients who are already HBeAg-negative, reduction in ALT and HBV DNA and the accompanying histological improvement are the endpoints.
Ideally successful treatment is characterised by a decline in HBV DNA to less than 15 IU/ml or levels undetectable by sensitive real time PCR. However, as there is no agreed threshold to define response, maintaining the response should be the objective.
In anti-HBe positive therapy, stopping points and finite courses of treatment are less commonly achieved because of higher rates of relapse in these patients. It is not clear if treatment can be halted even if HBV DNA remains