Prolonged Entecavir Therapy Is Not Effective for HBeAg Seroconversion in Treatment-Naive Chronic Hepatitis B Patients with a Partial Virological Response

Abstract

The aims of this study were to investigate the efficacy of prolonged entecavir (ETV) therapy in treatment-naive chronic hepatitis B (CHB) patients and to determine whether continuous ETV therapy is feasible to achieve HBeAg seroconversion, particularly in patients with partial virological response (PVR). A total of 142 treatment-naive patients with CHB were enrolled. The mean duration of treatment was 65 (range, 26 to 90) months, and 86 patients (60.6%) were HBeAg positive. PVR was defined as detectable hepatitis B virus (HBV) DNA (>116 copies/ml) at year 1. The cumulative incidence of virological response (VR) increased from 54.9% at year 1 to 98.2% at year 7. HBeAg positivity (odds ratio [OR], 4.146; P ‫؍‬ 0.001) and initial alanine aminotransferase (ALT) (OR, 0.997; P ‫؍‬ 0.004) were independent risk factors for PVR. Among the 64 patients with PVR, 47 patients (73.4%) achieved VR within 4 years after prolonged ETV therapy without treatment adaptation. Three patients (2.1%) experienced virological breakthrough and HBV variants with genotypic resistance. The cumulative rate of HBeAg seroconversion was significantly higher in the patients with VR than in the patients with PVR (P ‫؍‬ 0.018). None of the PVR patients with HBV DNA at >5,000 copies/ml at year 1 ever experienced HBeAg seroconversion. Multivariate analysis identified VR at year 1 as the only determinant of HBeAg seroconversion (hazard ratio [HR], 3.009; P ‫؍‬ 0.010). In conclusion, although there were patients with PVR, prolonged ETV therapy showed excellent VR, with only 2.1% emergence of viral resistance during a 7-year follow-up. However, to achieve HBeAg seroconversion, drug modification is needed for HBeAg-positive patients with PVR (especially those with HBV DNA at >5,000 copies/ml at year 1). C urrently, treatment guidelines for both HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB) patients recommend treatment with pegylated interferon or nucleos(t)ide analogs (NAs) (1-4). Although pegylated interferon has advantages, including a finite treatment duration and the absence of viral resistance, adherence to treatment is poor due to frequent side effects and the need for frequent subcutaneous injections (5). Given the increased risk of virological failure from poor adherence to pegylated interferon treatment, NAs have been widely used in clinical practice. Among several NAs, entecavir (ETV) and tenofovir (TDF) are especially potent inhibitors of hepatitis B virus (HBV) reverse transcriptase and DNA polymerase with minimal or no drug resistance (6-8). Therefore, ETV has been confidently used as a first-line therapy. Despite its efficacy, about 10 to 20% patients treated with ETV showed partial virological response (PVR) (9, 10). Unfortunately, HBV cannot be eradicated, and NAs must be continued until HBsAg seroclearance. Sustained viremia may ultimately result in HBV variants with genotypic resistance and clinical breakthrough. Therefore, it is related to subsequent therapeutic failure. In contrast to the frequently described genotypic re...

Efficacy and Safety of Entecavir 0. 5 mg in Treating Naive Chronic Hepatitis B Virus Patients in Egypt: Five Years of Real Life Experience

“…Similarly, in an earlier study prolonged ETV therapy was not found very effective in achieving HBeAg seroconversion in treatment-naive CHB patients with a partial virological response. In their study partial virological response was defined as detectable HBV DNA (> 116 copies/mL) at year one [ 28 ]. The two cases received consolidation treatment for 1 year after confirming HBeAg seroconversion on two different occasions 3 months apart.…”

5-year efficacy of entecavir in Indian patients with chronic hepatitis B

“…This is shown in other reports also [7]. Loss of HBsAg is rare [16,18]. There were some drawbacks of our study.…”

“…Our study showed maximum decline in HBV DNA starting earlier at 6 months which may be due to the lesser number of cirrhotics and good drug compliance. The high rate of HBV DNA negativity at 1 year (85.7 % [11], 96 % [12], 86.1 % [13]) and after prolonged therapy (92 % at 5 years [3], 95 % at 39 months [14], 83.7 % at 4 years [15], 98.2 % at 7 years [16]) is reflected in many other Asian studies. Studies from other parts of the world show that with 3-5 years of entecavir administration, the serum HBV DNA negativity rate was 55 % to 88 % at 1 year, 83 % to 93 % at 2 years, 89 % to 95 % at 3 years, 91 % to 96 % at 4 years and 94 % at 5 years.…”

“…This indicates its ineffectiveness in clearing the cccDNA which is regarded as the hallmark of complete viral [5,7,16,19]. In such studies, a HBV DNA cutoff level of 20 to 2000 IU/mL was considered for stopping or restarting therapy.…”

Upgrade Combination Response Is Limited by Prolonged Nucelos(t)ide Analogue Therapy in HBeAg-positive Chronic Hepatitis B: A Real-life Study

“… 17 In an ETV 7-year treatment study, HBeAg/anti-HBe seroconversion rates at years 3 and 7 were 26.7% and 37.5%, respectively. 18 Additionally, many investigations have shown that ETV and LDT have a higher rate of HBeAg/anti-HBe seroconversion in patients with HBeAg-positive CHB. 19 – 24 Therefore, in an analysis of the efficacy of long-term antiviral drug therapy, the combination response showed no strong trend with the virological response or chemical remission.…”