Study Of Predictors Of Virological Breakthrough To Chronic Hepatitis B Treated In Nucleos(t)ide Analogues

Objective: Nucleos(t)ide analogues(NAs) has been widely used in thetreatment of chronic hepatitis B, due to its powerful viral suppression、welltolerated、less adverse reaction and more conveinent to use. In order to achievethe ideal effect, primary non-response、 virological breakthrough andNAs-resistance which always trouble us became the focus of the optimizationof NAs. The purpose of this study was to evaluate the rate of virologicalbreakthrough in routine clinical practice and explore its predictors, whichaimed at optimize the therapeutic strategy of nucleos(t)ide.Methods:233inpatients and outpatients were recruited from February2003to December2010, which came from the Third Hospital of HeBeiMedical University and the Fifth Hospital of Shijiazhuang. All the patientsincluded hepatitis B virus-related liver cirrhosis and chronic hepatitis B. Thenumbers of hepatitits B e antigen(HBeAg)-positive and negative patients were139、94, respectively. The numbers of patients treated with lamivudine(100mgdaily)、 telbivudine(600mg daily)、 adfovir dipivoxil(10mg daily)、lamivudine(100mg daily) in combination with adfovir dipivoxil(10mg daily)and entecavir(0.5mg daily) were87、17、41、40、48, respectively. ALT level、Serum HBV markers、HBV DNA load、alpha fetoprotein（AFP）、 abdomenultrasonography or imageological examination were determined before andduring treatment. According to patient’s particular case gave liver histologyexamination. The established endpoint of our study was virologicalbreakthrough. The data was analyzed by SPSS16.0.Results:1Virological response rates in rutine clinical practiceIn routine clinical practice, the cumulative rates of complete virologicalresponse were42.9%,65.7%,77.7%,81.5%and81.5%after12,24,48,72 and96weeks therapy, respectively, a total of190patints. While62patients ofthem experienced virological breakthrough, a cumulative rate of4.7%,13.7%,22.6%,29.5%and32.6%after1,2,3,5,8years’ therapy. The rate ofvirological breakthrough in settings of lamivudine, telbivudine, adefovirdipivoxil, entecavir and lamivudine in combination with adfovir dipivoxilwere69.4%,33.3%,22.7%,5.6%,0%, respectively.2Adherence to NAs treatment for all patientsAmong all the recruitions,57(23.1%) patients were reported to benon-adherent.30of the57patients have been answered the questionaire,the most common reasons for non-adherence were forgetful(62%), financialdifficulties(19%) and adverse effects(10%). The others9%.3Predictors for virological breakthrough during NAs therapy190(81.5%) patients achieved complete virological response amongmembers included in this study during NAs therapy. After univariate andmultivariate Logistic regression analysis for base line characters andvirological response（αentry=0.05，αremoval=0.10）, which had been assignednew value, therapy (OR=0.358, P<0.001), higher baseline HBVDNA(>107copies/ml, OR=2.356, P=0.036), early virologicalresponse(OR=4.173, P=0.001), non-adherence(OR=2.740, P=0.039) wereimpact factors for virological breakthrough. In41patients with baselinehistologic diagnosis （αentry=0.10，αremoval=0.15）, therapy(OR=0.220,P=0.008), non-early virological response(OR=19.162, P=0.009) were impactfactors for virological breakthrough. In40patients who detected HBsAg,After univariate Logistic regression analysis for base line HBsAg, found theimpact of baseline HBsAg to virological breakthrough were notsignificant(P=0.198). While in37patients who had detected HBsAg at12thweeks（αentry=0.10，αremoval=0.15）, therapy(OR=0.108, P=0.045), non-earlyvirological response(OR=9.312, P=0.062) and higher HBsAg at12thweeks(>1500IU/ml, OR=9.990, P=0.045) were risk factors for virologicalbreakthrough.4Impact factors for maintained virological response Among190patients achieved complete virological response. Assign the62patients experienced virological breakthrough as1, whose durition ofmaintained virological response vary from24to384; While assign the rest128patients with new valu of0. We made the follow-up after completevirological response as time line, and Designed virological breakthrough assetting time. After Log-rank, χ2, and Cox proportional hazards modelanalysis(αentry=0.05，αremoval=0.06), therapy (HR=0.481, P<0.001), non-earlyvirological response(HR=3.624， P<0.001), non-adherence (HR=3.626，P<0.001) were impact factors to virological breakthrough.Conclusions:1However NAs can efficiently inhibit HBV replication, the rate ofvirological breakthrough gradually increase as therapy extend..2Therapy, HBV DNA level at base line and12thweek, adherence andHBsAg level at the12thweek are predictors for virological breakthrough.3Therapy, wether have achieved early virolgical response and adherenceare predictive factors for the duration of maintained virological response.4Adherence are important to the long-outcome of CHB patients treatedwith NAs, which is controllable factor. However, improvement of patient’sadherence rely on the cooperation of medical care providers and patientsthemselves.