| BACKGROUND AND AIMS:Hepatitis B virus(HBV) infection remains a major health problem. Patients with chronic hepatitis B(CHB) can be successfully treated using nucleos(t)ide analogous(NA). Being a new NA, Telbivudine(LdT) has demonstrated high antiviral efficacy. The patients' clinical characteristics at baseline and the virological response(VR) at week 24 can predict for VR and drug-resistance at week 52.The aim of the study was further to evaluate the efficacy and safety of LdT in CHB patients, and to determine whether VR at week 12 and week 24 can predict the efficacy and drug resistance at week 52.OBJECTIVE Forty two CHB patients(34 males and 8 females) aged 18 to 58 years, including 6 hepatitis B e antigen(HBeAg) negative cases, were enrolled. Criteria for inclusion were alanine transaminase(ALT) levels> 1.3×upper limit of normal (ULN) and<10×ULN at the start.METHODS All patients received LdT 600mg once daily for 52 weeks. Clinical characteristics were detected and analyzed at baseline. The levels of ALT, interleukin(IL)-2, IL-6 and quantity of hepatitis B surface antigen (HBsAg), HBeAg and HBV DNA were examined and analyzed at three months intervals. At the end of the study, genotypic resistances were determined in 8 patients in whom virological relapse occured.RESULTS 1. LdT is well tolerated. Forty patients finished the 52-week treatment. Two men with the elevation of creatine kinase and pain in muscle discontinued.2. Four HBeAg negative patients achieved the complete VR. Three (8.3%) patients achieved HBeAg seroconversion.3. At the end of 52-week study, drug-resistance happened in 8 patients(19.5%) in whom the virus genotype was all genotype C. Three patients had HBV mutation rtM204I,4 had a combined mutation of rtM204I and L80(L80V in 2 cases and L80I in 2 cases), and 1 patient had rtM204I, L80 and L180M HBV mutations.4. Four out of 9 HBeAg positive patients with a baseline HBV DNA >109 copies/ml and 2 out of 27 patients with a baseline HBV DNA< 109 copies/ml developed resistance. The resistance rate was significantly higher(P=0.024) in the former(44.4%) than in the latter(7.4%).5. For HBeAg positive patients,8 out of 10(80%) and 4 out of 18(22.2%) with HBV DNA level<1000 copies/ml and> 10000 copies/ml respectively at week 12 had HBV DNA<300 copies/ml at week 52(P=0.036). Patients who achieved HBV DNA<300 copies/ml,<1000, or>10000 copies/ml respectively at week 24, obtained complete VR rate 21.4%(3/14),0(0/4) and 0(0/12) respectively, HBV DNA negative rate 92.9%(13/14),25%(1/4) and 0%(0/12) respectively, and resistance rate 0(0/14),50%(2/4) and 41.7%(5/12) respectively. Significant difference existed among groups(p=0.036).6. There are significant differences at week 12 and week 24 in quantity of HBeAg, HBeAg loss and seroconversion among the patients who achieved complete or partial VR and those who developed mutations(P<0.05).7. The levels of IL-2 between HBeAg positive patients who achieved complete VR and the others. At week 24, difference was also noticed between patients who achieved partial VR and those who developed resistance (P<0.05).The levels of IL-2 and IL-6 elevated during the treatment. The levels of IL-6 between the patients with complete VR and mutations were different(p=0.003) at week 52.CONCLUTIONS1. The pretreatment HBV-DNA levels of HBeAg positive patients is related with the outcomes at week 52.2. The level of HBV-DNA at week 12 and week 24 were predictors of HBV-DNA<300 copies/ml and mutations of HBeAg positive patients.3. The levels of HBeAg, HBV DNA and HBeAg loss and seroconversion, IL-2 of HBeAg positive patients forecasted the response at week 52. |
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