Lamivudine vs lamivudine and interferon combination treatment of HBeAg(−) chronic hepatitis B

To determine whether combination treatment of HBeAg(−) chronic hepatitis B is beneficial we studied 78 patients with HBeAg(−), HBV DNA‐positive chronic hepatitis B who were randomized to lamivudine, 100 mg, qd, for 12 months or lamivudine–interferon (9 MU, t.i.w.) in combination. In the combination arm, 2 months of lamivudine treatment preceded 10 months of combination treatment. Biochemical, virologic and histologic responses were assessed at the end of treatment, after six and a median 27 months of drug‐free follow‐up (short‐ and long‐term follow‐up, respectively). Virologic response was defined as undetectable HBV DNA with a hybridization assay and biochemical response as normal alanine aminotransferase (ALT). Change in HBV DNA was also assessed by real‐time polymerase chain reaction (PCR). Presence of YMDD mutants at the end of treatment was investigated with a line probe assay. Both treatment regimes led to a median 2 log decline in HBV DNA levels. Virologic end of treatment responses were 90 and 92% with mono‐ and combination treatment, respectively. Corresponding virologic responses at short‐ and long‐term follow‐up were 59 and 54%, and 27 and 25%, respectively. Patients having a baseline HBV DNA value ≥200 pg/mL were more likely to relapse within 6 months off therapy than those patients with a baseline HBV DNA level