| Objective: To investigate the relationship of age,sex, HBeAg, HBVDNA, ALT, genotype and gene mutations at baseline with the initial virological response of nucleoside analogs in chronic hepatitis B.Methods:68 patients with chronic hepatitis B received lamivudine(LAM 100mg/d),adefovir dipivoxil(ADV,10 mg/d),tebivudine(LDT,600mg/d)for over half a year initial treatment, were prospectively investigated. The ALT level,HBVDNA,HBV marks were tested at baseline and every 1 month after therapy,every 3 month after HBVDNA<1.0×103 copies/mL ; HBV genotype was detected by nested PCR with multiple pair primers,mutations of polymerase(P), core genes(C),envelope gene(S),X gene(X),basal core promoter(BCP), precore(PC)were identified by PCR gene sequence analysis.Results:(1)The virological response rate at 3th month in the patients with 16 to 35 years (61.5%)was higher than that with 50 to 70 years(12.2%)(P=0.037);there were no apparently relationship between the sex and initial virological response at 3th,6th month(P>0.05); (2) there were no apparently relationship between HBVDNA,HBeAg,ALT level at baseline and initial virological response at 3th, 6th month(P>0.05);(3)In the 68 patients ,HBV genotypes mainly were genotype C(63.2%)and genotype B(22.1%),in addition, 5 patients with genotype B+D,and 4 patients with genotype B+C and 1patient with genotype C+D, the genotype A,E,F,G,H were not discovered; There were no statistically significant difference between the HBV genetype and initial virological response(P>0.05)(4)The virological response rate at 3th month in the group of LDT(100.0%)was higher than that in the LAM group(42.1%)(P=0.001)and ADV group(50.0%)(P=0.011); but there were no statistically significant difference between these 3 groups and 6th virological response(P>0.05); (5)Among the 68 patients , HBV P gene mutations were detected in 4 cases(5.9%), including 1 case (1.5%)rtL180M with LAM treatment,2 case(3.0%)rtC198S with LAM and ADV respectively,1(1.5%)case rtV207L,all 4 cases obtained initial virological response ;⑹Among 68 patients, HBV C gene mutations were detected in the 38 patients (55.9%),there were 4 mutations sites, including Y38H(5.9%),L60V(19.1%),L101W(4.4%),P130I(39.7%) ; HBV S gene mutations were detected in the 23patients (33.8%),there were 5 utations sites, including S53L(30.9%), L77Q(2.9%), L98V(2.9%), G102P(1.5%), L104S(1.5%); HBV X gene mutations were detected in the 31 patients (45.6%),there were 5 mutations, including G35W(13.2%),A40S (2.9%),P46T (2.9%),A66T (14.7%),T81P (23.5%);HBV BCP gene mutations were detected in the 51 patients (75.0%),there were 8 mutations,including G1721A (32.3%),A1726C (8.8%),A1752G (4.4%),T1758G (50.0%),A1762T (7.4%),G1764A (8.8%),A1775G(36.7%),G1799C (110.3%)(P>0.05); HBV PC gene mutations were detected in the 31 patients (45.6%),there were 5 mutations, including T1858C(25.0%),G1896A(10.3%),G1899A(14.7%),T1916C(5.9%),T1918A(13.2%); there were no significant relationship between above mutations and initial virological response (P>0.05).Conclusion:(1)The genotype in Guangxi CHB patients wasn't the influencing factor on initial virological response with nucleoside analogs treatment. (2)The younger ,the easier obtained virological response at the 3th month;(3) the 6th month virological response can be regarded as a reasonable point to predict antiviral response ; (4) HBV P gene mutation rtL180M in pretherapy may not led to LAM primary resistance, rtC198S and rtV207L mutations didn't influence on initial virological response of LAM and ADV; (5)HBV C gene mutations ( Y38H,L60V,L101W,P130I ),S gene mutations( S53L,L77Q,L98V,G102P,L104S), X gene mutations(G35W,A40S,P46T,A66T,T81P), BCP gene mutations (G1721A,A1726C,A1752G,T1758G,A1762T,G1764A,A1775G,G1799C ), PC gene mutations(T1858C,G1896A,G1899A,T1916C,T1918A )didn't show obvious relationship to initial virological response of nucleoside analogs treatment. |
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