On‐treatment monitoring of adefovir therapy in chronic hepatitis B: virologic response can be assessed at 24 weeks

Abstract

Patients with chronic hepatitis B (CHB) who will and those who will not respond to adefovir (ADV) monotherapy need to be identified at an early stage in order to adjust treatment and prevent future development of antiviral resistance. In a single-centre cohort study, we investigated 76 CHB patients [50% hepatitis B e antigen (HBeAg)-positive] treated with long-term ADV monotherapy. During a median follow-up of 122 (24-185) weeks, 42 (55%) patients achieved virologic response (VR), defined as HBV-DNA levels <10(3) copies/mL, and 10 patients (13%) developed genotypic ADV resistance. Independent baseline predictors of VR were HBeAg negativity [hazard ratio (HR) 2.98; 95% confidence interval (CI) 1.24-7.19; P = 0.02], high alanine aminotransferase (ALT) levels (HR 1.11; 95% CI 1.05-1.18; P = 0.001), and low HBV-DNA levels (HR 0.56; 95% CI 0.41-0.75; P < 0.001). HBV-DNA at week 24 demonstrated a higher predictive value for VR than HBV-DNA at week 48. Important predictors of genotypic resistance were presence of cirrhosis (HR 6.54; 95% CI 1.39-30.9; P = 0.018), and not achieving VR during treatment (HR 6.60; 95% CI 1.35-32.4; P = 0.008). Patients without VR at week 24 already demonstrated a trend towards the emergence of ADV resistance (P = 0.07). HBV-DNA at week 24 was a better on-treatment predictor of VR than HBV-DNA at week 48, and ADV-resistant mutations developed more frequently in patients without VR at week 24. Therefore, our study suggests that virologic response to ADV therapy can be assessed at 24 weeks, instead of the generally recommended 48 weeks.

On-treatment monitoring of HBV DNA levels: predicting response and resistance to oral antiviral therapy at week 24 versus week 48

“…In addition, Pritchett et al [15] reported that lamivudine-resistant patients who had a more than 50% reduction in serum HBV DNA levels at week 24 of adefovir treatment were more likely to have undetectable serum HBV DNA levels at 1 year. In a single-center cohort study involving 76 patients with CHB treated with long-term adefovir monotherapy, serum HBV DNA levels at week 24 demonstrated a higher predictive value for virologic response at week 122 than serum HBV DNA levels at week 48 [10]. Of note, patients without undetectable serum HBV DNA levels at week 24 demonstrated a trend toward the emergence of adefovir resistance (P = 0.07).…”

“…More recently, several studies have shown that serum HBV DNA levels at 24 weeks of adefovir are predictive of favorable outcomes in patients with CHB receiving adefovir [10,15,40]. In an adefovir-controlled, randomized, open-label trial of telbivudine involving 135 treatment-naive, HBeAg-positive adults with CHB, undetectable serum HBV DNA levels at week 24 were associated with high rates of virologic response at week 52 [40].…”

“…The development of highly sensitive polymerase chain reaction-based assays for the quantification of serum HBV DNA has facilitated the investigation of the relationship between early virologic response to oral NA therapy and treatment outcomes. Early virologic response to oral NA therapy has been shown to correlate with favorable outcomes to therapy [5][6][7][8][9][10][11][12][13][14][15][16]. More specifically, substantial evidence has established that serum HBV DNA levels at week 24 or 48 of treatment are predictive of sustained virologic response, normalization of alanine aminotransferase (ALT) levels, hepatitis B e antigen (HBeAg) seroconversion, and the risk of developing antiviral resistance [5][6][7][8][9][10][11][12][13][14][15][16].…”

“…Early virologic response to oral NA therapy has been shown to correlate with favorable outcomes to therapy [5][6][7][8][9][10][11][12][13][14][15][16]. More specifically, substantial evidence has established that serum HBV DNA levels at week 24 or 48 of treatment are predictive of sustained virologic response, normalization of alanine aminotransferase (ALT) levels, hepatitis B e antigen (HBeAg) seroconversion, and the risk of developing antiviral resistance [5][6][7][8][9][10][11][12][13][14][15][16]. On the basis of these findings, the ''roadmap'' treatment strategy was developed, advocating the monitoring of serum HBV DNA levels at weeks 12 and 24 of treatment to identify primary nonresponse and partial virologic response, respectively, and to modify treatment accordingly [17].…”

“…Similarly, the identification of on-treatment predictors of response and resistance to oral NA therapy has gained considerable interest as a means of optimizing treatment regimens and therapeutic outcomes [23][24][25]. Substantial data regarding on-treatment predictors of response and resistance to lamivudine, adefovir, and telbivudine in patients with CHB have been reported in the literature [5][6][7][10][11][12][13][14]. Limited data on predictors of response for entecavir and tenofovir have been published [9,16].…”