Partial virological response to three different nucleotide analogues in naive patients with chronic hepatitis B

BACKGROUND： The definition of partial virological response （PVR） was proposed because of its clinical relevance. PVR relates to subsequent therapeutic failure which results in the modification of the regimen. Whether this rationale can be applied to all nucleotide analogues （NA） is not clear. This study was undertaken to analyze PVR influence on therapeutic outcomes during lamivudine, entecavir or tenofovir mono- therapy in NA-naive patients with chronic hepatitis B in routine clinical practice. METHODS： We retrospectively analyzed 150 NA-naive patients with chronic hepatitis B. These subjects received lamivudine, entecavir or tenofovir monotherapy between February 2001 and July2013. RESULTS： Sixty-nine patients were treated with lamivudine, 35 with entecavir, and 46 with tenofovir. The median therapeutic duration was 19.5 （6-147） months. PVR rates at 24 weeks were similar among three NAs （lamivudine 33.3%, entecavir 35.0%, tenofovir 32.4%, P--0.981）. For all three NAs, patients with a higher baseline viral load or HBeAg-positive status had a higher serum viral positive rate tested by polymerase chain reaction at week 24 and 48. Cumulative probability of virological breakthrough （VBR） for patients treated with lamivudine was 67% at 5 years, and PVR at 24 weeks was the independent risk factor for VBR （HR： 3.09; 95% CI： 1.09-8.74; P=0.034）; also lamivudine treated patients older than 50 years seemed to have a tendency for VBR （HR： 2.80; 95% CI： 0.99-8.18; P=0.052）. A majority of entecavir and tenofovir partial responders achieved and maintained virological response with prolonged monotherapy, except one entecavir treated patient who experienced VBR due to resistance mutations.CONCLUSIONS： Management strategy for lamivudine treatment should include adaptation of regimen according to PVR as an on-treatment response parameter due to its relation with unacceptably high VBR probability. Similar conclusion should not be directly related to entecavir or tenofovir treatment.

Efficacy of Real-world Entecavir Therapy in Treatment-naive Chronic Hepatitis B Patients

Background：Entecavir （ETV） has been shown to be effective in randomized controlled trials in highly selected patients with hepatitis B virus （HBV） infection.This study aimed to evaluate the efficacy of ETV in chronic hepatitis B （CHB） patients in the real-world setting.Methods：A total of 233 treatment-na（i）ve,CHB patients who received at least 12 months of ETV treatment were included in this retrospective study.Rates of virological response （VR）,hepatitis B s antigen （HBsAg） loss,hepatitis B e antigen （HBeAg） clearance/seroconversion,virological breakthrough,cirrhosis,and hepatocellular carcinoma were evaluated.Results：Of 233 patients,175 patients were male,with mean age of 43 years old,and 135 patients were HBeAg positive.The mean baseline levels of serum alanine aminotransferase and HBV DNA in all patients were 230 U/L and 6.6 log 10 IU/ml,respectively.The mean follow-up period was 28 months.The cumulative rates of achieving VR increased from 3.4% at 3 months to 94.4% at 60 months.Primary nonresponse occurred in 3 （1.3%） patients.Partial VR （PVR） occurred in 61 （26.2%） patients at 12 months.The baseline serum HBV DNA level （hazard ratio [HR],2.054;P 〈 0.001） was an independent risk factor for PVR.HBsAg loss did not occur.The cumulative rates of HBeAg clearance increased from 2.2% at 3 months to 28.2% at 60 months.PVR was the significant determinant of HBeAg clearance （HR,0.341;P =0.026）.Age （HR,1.072;P =0.013） and PVR （HR,5.131;P =0.017） were the significant determinants of cirrhosis.Conclusions：ETV treatment was effective for HBV DNA suppression in this study,but HBsAg loss and HBeAg clearance/seroconversion rates were lower compared with previous clinical trials.PVR was associated with HBeAg clearance and cirrhosis.