Combination of Lamivudine and adefovir therapy in HBeAg-positive chronic hepatitis B patients with poor response to adefovir monotherapy

Abstract

At present, there is no consensus treatment for patients who have poor response to Adevofir dipivoxil (ADV) monotherapy and no ADV-associated mutation. The purpose of this study was to evaluate the effect of a new therapeutic strategy combining Lamivudine (LAM) and ADV in patients with HBeAg-positive chronic hepatitis B (CHB) and poor response to ADV monotherapy. Thirty-one patients with chronic hepatitis B with HBV DNA > or = 10(4) copies/mL after 48 weeks of ADV monotherapy were included and received ADV plus LAM for 24 weeks. Compared with ADV monotherapy, ADV + LAM had an improved response rate at weeks 12 and 24 - compared with baseline, the median decrease in HBV-DNA level at week 12 and 24 were 1.27 and 2.03 log respectively. The virological response (VR) rate (HBV-DNA level <10(3) copies/mL) was 6.5% and 35.5% at weeks 12 and 24, respectively; the biochemical response (BR) rate (normalization of alanine aminotransferase levels) was 67.8% and 100%, respectively; the HBeAg loss rate was 6.9% and 34.5%, respectively; and the seroconversion rate (from HBeAg to HBeAb) was 3.5% and 6.9% respectively. No ADV-associated mutation was detected at baseline. After combination therapy for 24 weeks, no LAM-resistant or ADV-resistant mutations were detected. Only one patient had a mild adverse reaction. In conclusion, optimization of therapy combining LAM and ADV may be a good choice for patients with hepatitis B who have a poor response to ADV monotherapy.

Lamivudine plus Adefovir or Telbivudine plus Adefovir for Chronic Hepatitis B Patients with Suboptimal Response to Adefovir

“…In the present study, we provided a head-to-head comparison of LdT+ADV with 3TC+ADV in CHB patients with suboptimal response to ADV, and we found that both 3TC+ADV and LdT+ADV treatments produced greater HBV DNA suppression and higher rates of ALT normalization. As compared to our previous study on HBeAg-positive patients with suboptimal response to ADV [25], the virological response rate of patients in the present study was significantly increased, which might be correlated to the lower baseline viral load when another NA was added. Experience from the management of NA-resistance patients suggested that combination therapy could significantly delay or prevent the emergence of drug resistance [27,28].…”

“…However, data on the comparison of different combination strategies is rare. Previously, our two independent short-term studies on patients with poor response to ADV demonstrated that higher proportions of patients in the LdT+ADV group achieved a virological response at week 24 than did patients in the 3TC+ADV group (66.7% [16/24] versus 35.5% [11/31]) [25,26].…”

Resolution of adefovir‐related nephrotoxicity by adefovir dose‐reduction in patients with chronic hepatitis B

“…It is intriguing that despite dose reduction, our patients with renal dysfunction had no significant increase in HBV DNA, suggesting that the efficacy of adefovir in such patients may have been more profound, some 90% of these patients were HBV DNA‐negative compared to only 66% who did not have adefovir‐related abnormal serum creatinine. This observation could be important as adefovir is considered a relatively weak antiviral agent against hepatitis B virus, and poor responders have been documented …”

Efficacy of telbivudine treatment for hepatitis B e antigen‐positive chronic hepatitis B patients with poor response to adefovir dipivoxil

“…Combination therapies are suggested to delay or prevent drug resistance and may offer a potential action for the management of suboptimal response to monotherapy [28][29][30]. Adding on LAM in patients with poor response to ADV could markedly decrease the level of HBV DNA with 2.03 log 10 copies/mL, as well as improve the response rates with 35.5% in VR and 100% in BR at 24 weeks [21]. Chen et al [31] also evaluated two different combination therapies in patients with suboptimal response to ADV.…”

“…However, some patients revealed insufficient or poor response for initial ADV therapy after 24–48 weeks. This is partly because of the suboptimal doses, high pretreatment HBV DNA levels and ADV‐resistant variants . Thus, it is strongly recommended that therapies should be optimized by detection of serum HBV DNA during NAs treatment and 48 weeks after initial treatment is the most important time point to assess effect in ADV therapy .…”