A Low Viral Load Predicts a Higher Initial Virologic Response to Adefovir in Patients with Lamivudine-Resistant Chronic Hepatitis B

Abstract

Background/Aims: Adefovir (ADV) is the preferred drug for treating lamivudine (LAM)-resistant hepatitis B. However, not all patients who face virologic breakthrough during LAM treatment respond to ADV. The aim of this study was to determine the factors associated with efficacy of ADV in LAM-resistant hepatitis B patients. Methods: The medical records of 231 patients who received ADV due to LAM-resistance were reviewed. Efficacy was assessed by the initial virologic response (IVR), defined as hepatitis B virus (HBV) DNA not being undetectable by real-time PCR at 6 months of ADV treatment. Results: Seventy patients (30%) achieved IVR. While 'add-on' modality, hepatitis B e antigen (HBeAg) negativity, and low baseline HBV DNA levels were associated with IVR in univariate analysis, multivariate analysis revealed HBeAg status and the DNA level to be the significant factors. The probability of IVR achievement increased sharply per each log10 copies/mL decrement in the baseline viral load, which was 133 times in patients who had HBV DNA ＜10 5 copies/mL compared with those who had ≥10 8 copies/mL. Conclusions: Factors associated with the IVR were HBeAg negativity and a low baseline viral load. Therefore, when virologic breakthrough with genotypic resistance emerges during LAM therapy, ADV treatment should be considered immediately before further increases in viral load. Additional long-term follow-up data are warranted.(Gut Liver 2010;4:530-536)

Long‐term outcomes of add‐on adefovir dipivoxil therapy to ongoing lamivudine in patients with lamivudine‐resistant chronic hepatitis B

“…The rate of VR was 90.8% at 4 years of treatment. The strongest predictive factor for VR in both HBeAg positive and negative patients were confirmed by previous observations showing that add‐on ADV therapy achieves more rapid and higher rates of VR when ADV is initiated in LAM‐resistant patients with low viral replication levels 11–17 . We also found that lower Alb level was an independent predictive factor for VR in HBeAg positive patients.…”

“…The strongest predictive factor for VR in both HBeAg positive and negative patients were confirmed by previous observations showing that add-on ADV therapy achieves more rapid and higher rates of VR when ADV is initiated in LAM-resistant patients with low viral replication levels. [11][12][13][14][15][16][17] We also found that lower Alb level was an independent predictive factor for VR in HBeAg positive patients. In fact, baseline Alb correlated with PLT counts (r = 0.51, P < 0.001) and T-Bil (r = -0.38, P < 0.001), indicating that a lower Alb level reflected progression of liver disease.…”

The Feasibility of Discontinuing Lamivudine in Lamivudine-Resistant Chronic Hepatitis B Patients on Lamivudine and Adefovir Combination Therapy

“…LAM + ADV combination therapy) showed significantly less ADV resistance than ADV single therapy (LAM to ADV switch therapy) [15,16,17,18,19,20]. However, it has not yet been studied if once a VR is attained with LAM + ADV combination therapy, administration of LAM should be combined indefinitely or could actually be discontinued [21,22,23,24]. Moreover, LAM and ADV are no longer first-line drugs for CH-B patients in many countries since the introduction of entecavir (ETV) and tenofovir (TDF), both of which show higher antiviral potency and a higher resistance barrier than LAM or ADV.…”

“…So, according to their economic conditions, these patients had only the option of self-paid LAM and insurance-covered ADV for the LAM + ADV combination therapy or a discontinuation of LAM with insurance-paid ADV monotherapy [23,25]. Therefore, after achieving VR, many were willing to discontinue the self-paid LAM.…”

Mutational analysis of reverse transcriptase and surface proteins of patients with partial virological response during mono and combination antiviral therapies in genotype D chronic hepatitis B

“…According to the guidelines of clinical practice, a decrease in HBV DNA of more than 1 log10 IU/ml from the baseline pre-treatment is defined as partial virological response ( 21 ). Previous studies have been conducted using different protocols for alternate cross regimen in partially-responsive patients based on new NA drugs ( 22 – 25 ).…”