Tenofovir disoproxil fumarate monotherapy for nucleos(t)ide analogue-naïve and nucleos(t)ide analogue-experienced chronic hepatitis B patients

Abstract

Background/aims: This study investigated the antiviral effects of tenofovir disoproxil fumarate (TDF) monotherapy in nucleos(t)ide analogue (NA)-naive and NA-experienced chronic hepatitis B (CHB) patients.

Methods: CHB patients treated with TDF monotherapy (300 mg/day) for ≥12 weeks between December 2012 and July 2014 at a single center were retrospectively enrolled. Clinical, biochemical, and virological parameters were assessed every 12 weeks.

Results: In total, 136 patients (median age 49 years, 96 males, 94 HBeAg positive, and 51 with liver cirrhosis) were included. Sixty-two patients were nucleos(t)ide (NA)-naïve, and 74 patients had prior NA therapy (NA-exp group), and 31 patients in the NA-exp group had lamivudine (LAM)-resistance (LAM-R group). The baseline serum hepatitis B virus (HBV) DNA level was 4.9±2.3 log IU/mL (mean±SD), and was higher in the NA-naïve group than in the NA-exp and LAM-R groups (5.9±2.0 log IU/mL vs 3.9±2.0 log IU/mL vs 4.2±1.7 log IU/mL, P<0.01). The complete virological response (CVR) rate at week 48 in the NA-naïve group (71.4%) did not differ significantly from those in the NA-exp (71.3%) and LAM-R (66.1%) groups. In multivariate analysis, baseline serum HBV DNA was the only predictive factor for a CVR at week 48 (hazard ratio, 0.809; 95% confidence interval, 0.729-0.898), while the CVR rate did not differ with the NA experience.

Conclusions: TDF monotherapy was effective for CHB treatment irrespective of prior NA treatment or LAM resistance. Baseline serum HBV DNA was the independent predictive factor for a CVR.

Keywords: Chronic Hepatitis B; Lamivudine-resistant; Nucleos(t)ide analogue-experienced; Tenofovir.

Figure 1. Mean changes in serum HBV DNA level during TDF treatment.

HBV, hepatitis B virus; NA, nucleos(t)ide analogue; LAM-R, lamivudine resistance.

Figure 2. Cumulative probability of CVR to TDF according to variables. (A) omparison of CVR rate according to NA-experience. CVR rate in NA-naïve group was not significantly different from that in NA-exp group or LAM-R group. (B) Comparison of CVR rate according to HBeAg status. CVR rate was significantly higher in HBeAg negative patients than HBeAg positive patients. (C) Comparison of CVR rate according to baseline serum HBV DNA. CVR rate was significantly higher in patients with serum HBV DNA <4.3 log IU/mL than those with serum HBV DNA ≥4.3 log IU/mL. CVR, complete virological response; TDF, tenofovir disoproxil fumarate; NA, nucleos(t)ide analogue; LAM-R, lamivudine resistance.

Figure 3. Cumulative probability of a CVR to TDF according to baseline serum HBV DNA. (A) CVR in patents with baseline serum HBV DNA <4.3 log IU/mL. CVR in NA-naïve patients (n=13, 92.3%) was not significantly different from that in NA-exp group (n=43, 85.8%), or LMV-R group (n=15, 92%). (B) CVR in patents with baseline serum HBV DNA ≥4.3 log IU/mL, CVR in NA-naïve patients (n=49, 65.2%) had tendency to be higher as compared with NA-exp group (n=31, 50.3%. P=0.117), or LMV-R group (n=16, 43%, P=0.063). CVR, complete virological response; TDF, tenofovir disoproxil fumarate; NA, nucleos(t)ide analogue; LAM-R, lamivudine resistance.

Figure 4. Cumulative probability of a biochemical response to TDF monotherapy. The biochemical response rate did not differ significantly between the NA-naïve group and the NA-exp group or the LAM-R group. TDF, tenofovir disoproxil fumarate; NA, nucleos(t)ide analogue; LAM-R, lamivudine resistance.