Partial Virological Response to Adefovir Add-On Lamivudine Rescue Therapy in Patients with Lamivudine-Resistant Chronic Hepatitis B

Abstract

Background/Aims: In patientswith lamivudine (LAM)-resistant chronic hepatitis B (CHB)receivingadefovir (ADV) add-on LAM therapy, insufficient viral suppression or the appearance of additional ADV resistance has remained unresolved. This study determined the partial virological response (PVR) criteria to predict a virological response (VR) at week 96 in these patients. Methods: 96 patients with LAM-resistant CHB (ADV add-on LAM therapy >2 years) were analyzed. For predicting VR at week 96, the area under the receiver operating characteristic curve values at different time points were compared to establish the optimal time point, and the maximal Youden index was calculated to determine the optimal cut-off hepatitis B virus (HBV) DNA level. Results: 50 (52.1%) patients achieved VR at 2 years after ADV add-on LAM therapy. The optimal PVR criteria were determined to be HBV DNA 500 IU/ml at week 48. 44 (45.8%) patients who met optimal PVR criteria showed a significantly higher risk for detectable HBV DNA levels at week 96 than those with a favorable VR (HBVDNA <500 IU/ml) at week 48. Conclusions: This study suggested optimal PVR criteria in patients with LAM-resistant CHB receiving ADV add-on LAM therapy. Modification of the antiviral agent regimen should be considered if the serum HBV DNA level exceeds 500 IU/ml at week 48.

Outcome of adefovir add‐on lamivudine rescue therapy of up to 5 years in patients with lamivudine‐resistant chronic hepatitis B

“…Although the area under the receiver operating characteristic curve (0.752) and sensitivity (49.3%) were relatively low, specificity (93.5%) was significantly high. In contrast to a previous study that proposed 500 IU/mL as the optimal cutoff HBV DNA level to predict CVR up to 2‐year rescue therapy, our cutoff (800 IU/mL) might have resulted from the longer follow‐up duration encompassing slow responders to ADV add‐on rescue therapy. Although a previous study with a 5‐year follow‐up suggested that 200 IU/mL at 6 months can be a useful predictor of long‐term virological suppression, these strict criteria might be subject to the risk of unnecessary NUC change.…”

“…15 Similar to the previous reports, 4.8% of the study population (n = 8) experienced renal impairment. 22,27,28 Based on a recent study suggesting that the optimal time point to predict CVR at 2 years was 1 year rather than 6 months for ADV add-on LAM rescue therapy, 1,2,20 and because our study aimed to assist in determining whether we should change ADV to other NUCs or not, we used HBV DNA level, reduction rate of HBV DNA during the first year, ALT level, and HBeAg positivity after 1 year of rescue therapy instead of at baseline as on-treatment variables to identify independent predictors of CVR during 5-year rescue therapy, together with baseline variables such as age, gender, liver cirrhosis, HBV DNA, and LAM duration. Finally, we found that only HBV DNA level at 1-year rescue therapy significantly predicted CVR during a 5-year period.…”

“…A recent study suggested new criteria for partial virological response in patients who received ADV add‐on LAM rescue therapy (500 IU/mL at 1 year of treatment) . However, a limited follow‐up period and the corresponding use of CVR at only 2 years of treatment might have lowered the cutoff HBV DNA level to select rapid responders and subsequently overestimated the proportion of patients with partial virological response.…”

“…1,2 A recent study suggested new criteria for partial virological response in patients who received ADV add-on LAM rescue therapy (500 IU/mL at 1 year of treatment). 20 However, a limited followup period and the corresponding use of CVR at only 2 years of treatment might have lowered the cutoff HBV DNA level to select rapid responders and subsequently overestimated the proportion of patients with partial virological response. Therefore, we tried to investigate the long-term antiviral efficacy of ADV add-on LAM rescue therapy and the optimal cutoff HBV-DNA level to predict CVR during 5-year antiviral treatment among patients who did not experience CVR at 1 year of treatment.…”