Factors that predict response and breakthrough phenomenon to lamivudine monotherapy in patients with HBeAg-negative chronic hepatitis B have not been well defined.


To determine pre-treatment and on treatment variables that predict initial response and breakthrough in patients with HBeAg-negative chronic hepatitis B receiving long-term lamivudine.


Seventy-nine patients, with chronic HBeAg-negative hepatitis B, who received lamivudine for a median of 31 months were included in the study.


Initial virologic and biochemical response was observed in 73 (92%) and 70 (89%) patients, respectively, while 34 (47%) and 15 (21%) patients developed virological and biochemical breakthrough, respectively. High levels of necroinflammation in liver biopsy were associated with a higher probability of initial virological and biochemical response. Patients with pre-treatment serum hepatitis B virus DNA concentrations of more than 106 copies/mL were three times more likely to develop virologic breakthrough. Two patients died, one with baseline cirrhosis because of liver failure during biochemical breakthrough while the second death was liver and treatment unrelated.


In HBeAg-negative chronic hepatitis B, initial response to lamivudine therapy is associated with necroinflammation, while baseline serum hepatitis B virus DNA exceeding 106 copies/mL is a strong predictor for breakthrough because of drug-resistant mutations. Severe complications are uncommon and are associated with biochemical breakthrough and pre-existing cirrhosis.