Clinical characteristics of patients with chronic hepatitis B who developed genotypic resistance to entecavir: Real-life experience.

BACKGROUND/AIMS: Clinical characteristics of patients with chronic hepatitis B (CHB) who developed genotypic resistance to entecavir (ETV) were compared to those without resistance. METHODS: Two hundred fifty eight CHB patients who underwent ETV treatment in our institution from July 2007 to May 2013 were included. RESULTS: Eight (3.1%) patients developed genotypic resistance to ETV during the follow-up period. The patterns of genotypic resistance to ETV were as follows: L180M + M204V + S202G (n=3); M204I + V173M (n=1); I169V + V173M (n=1); L180M + M204V + V173L (n=1); L180M + M204V + V173L + M250V (n=1); M204I + V214A + P237H (n=1). The cumulative occurrence rates of genotypic resistance to ETV were not significantly different between CHB patients with prior nucleos(t)tide analogues (NA) exposure (NA experienced, n=56) and NA naïve patients (n=202, P=0.823 by log rank comparison). Older age, higher baseline log10hepatitis B virus-deoxynucleic acid (log10HBV-DNA), higher log10HBV-DNA at 3, 6, 12 and 24 months after baseline, and complete virologic response (CVR, undetectable serum HBV-DNA by polymerase chain reaction 6 months after ETV treatment) were significant contributors to the development of genotypic resistance to ETV. Multivariate analyses showed higher log10HBV-DNA 6 months after baseline and absence of CVR were independent and significant contributors to the development of ETV resistance. CONCLUSIONS: Clinical characteristics of patients who developed ETV resistance were higher log10HBV-DNA 6 months after baseline and absence of CVR during the ETV treatment.

Clinical response to long-term tenofovir monotherapy in Korean chronic hepatitis B patients.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is a potent nucleotide analogue recommended as first-line monotherapy for chronic hepatitis B (CHB). We investigated the clinical response to TDF monotherapy in Korean CHB patients. METHODS: A total of 90 CHB patients [55 hepatitis B e antigen (HBeAg)-positive and 35 HBeAg-negative] who received TDF monotherapy for >2year, were enrolled. Quantitative hepatitis B surface antigen (qHBsAg) levels, serum alanine aminotransferase (ALT), HBeAg, anti-HBe and HBV DNA levels were measured during treatment. Virologic response (VR) was defined as undetectable HBV DNA level. RESULTS: The cumulative incidences of complete virologic response (CVR) were 75.6% and 89.9% at months 12 and 24, respectively. The cumulative CVR rates were significantly higher in HBeAg-negative than HBeAg-positive group (P<0.001). HBeAg loss/seroconversion was observed in 21 (38.2%) out of 55 HBeAg-positive patients. One HBeAg-positive and 1 HBeAg-negative patients (2.2%) achieved HBsAg loss at months 6 and 8 of TDF therapy, respectively. Baseline HBV DNA level and qHBsAg were significant predictive factors for a CVR (P=0.001 and P<0.001, respectively). CONCLUSIONS: Virologic, serologic, biochemical responses were achieved in both HBeAg-positive and HBeAg-negative patients under 24-month TDF therapy. Monitoring using baseline HBV DNA and qHBsAg levels would be helpful to predict CVR.

Clinical characteristics of patients with chronic hepatitis B who developed genotypic resistance to entecavir: Real-life experience

BACKGROUND/AIMS: Clinical characteristics of patients with chronic hepatitis B (CHB) who developed genotypic resistance to entecavir (ETV) were compared to those without resistance. METHODS: Two hundred fifty eight CHB patients who underwent ETV treatment in our institution from July 2007 to May 2013 were included. RESULTS: Eight (3.1%) patients developed genotypic resistance to ETV during the follow-up period. The patterns of genotypic resistance to ETV were as follows: L180M + M204V + S202G (n=3); M204I + V173M (n=1); I169V + V173M (n=1); L180M + M204V + V173L (n=1); L180M + M204V + V173L + M250V (n=1); M204I + V214A + P237H (n=1). The cumulative occurrence rates of genotypic resistance to ETV were not significantly different between CHB patients with prior nucleos(t)tide analogues (NA) exposure (NA experienced, n=56) and NA naïve patients (n=202, P=0.823 by log rank comparison). Older age, higher baseline log10hepatitis B virus-deoxynucleic acid (log10HBV-DNA), higher log10HBV-DNA at 3, 6, 12 and 24 months after baseline, and complete virologic response (CVR, undetectable serum HBV-DNA by polymerase chain reaction 6 months after ETV treatment) were significant contributors to the development of genotypic resistance to ETV. Multivariate analyses showed higher log10HBV-DNA 6 months after baseline and absence of CVR were independent and significant contributors to the development of ETV resistance. CONCLUSIONS: Clinical characteristics of patients who developed ETV resistance were higher log10HBV-DNA 6 months after baseline and absence of CVR during the ETV treatment.

Female is more likely to have complete virological response in Entecavir treatment among chronic hepatitis B patients with positive HBeAg / 中华临床感染病杂志

Objective To investigate the associated factors of complete virological response (CVR) in Entecavir treatment among chronic hepatitis B (CHB) patients with positive HBeAg.Methods Data of 166 CHB patients with positive HBeAg receiving Entecavir treatment in Yantai Infectious Diseases Hospital during December 2009 and May 2014 were collected.Clinical data including age,gender,genotype,baseline alanine aminotransferase (ALT),HBV DNA load,HBsAg and HBeAg levels as well as CVR cumulative rates at different time points during Entecavir treatment were retrospectively analyzed.The cumulative rate of CVR was estimated using Kaplan-Meier method,and the difference in cumulative CVR rates was studied with Log-rank test.Cox's proportional hazards regression model was used to analyze the factors associated with CVR during Entecavir treatment.Results The cumulative rates of CVR during Entecavir treatment in HBeAg positive CHB patients were 54.5％ (87/157),74.3％ (106/129),80.2％ (109/119) and 86.8％ (110/112) at 48,96,144 and 192 weeks,respectively.Log-rank test showed that female patients and patients with genotype B,high baseline ALT level or low baseline HBV DNA load had higher CVR rates (x2 =15.601,11.542,17.021 and 10.094,all P ＜ 0.01).Cox's proportional hazards regression model showed that female was the only associated factor for CVR in Entecavir treatment among HBeAg positive CHB patients [hazard ratio (HR) =3.015,95％ confidence interval (CI):1.875-4.968,P ＜ 0.01].Conclusion CVR rate is increasing with the course of Entecavir treatment in HBeAg positive CHB patients,and CVR is more likely to occur in female patients.