| Chronic hepatitis B is one of serious human's diseases.At present,there are at least 350 million patients with chronic HBV all over the world.Anti-viral treatment is the main means of treatment of chronic hepatitis B,In the past it was mainly IFN and LAM..The use of INF is limited because of IFN's many side effects and poor tolerability.Although the tolerability and safety of LAM is good, with the extension of the treatment,The incidence of drug-resistant increased gradually.Resently,there are more and more clinical LAM resistant patients,the emergence of ADV give us hope,but the situation of the efficacy and ADV-resistance about ADV treatment on LAM-resistant chronic hepatitis B patients has been little reported.In order to explore the therapeutic effect and ADV resistance variation of LAM-resistant and HBeAg(+) Chronic Hepatitis B and provide better reference value for clinical treatment.149 cases of HBeAg-positive lamivudine resistance and viral load＞5log10copies/ml chronic hepatitis B patients(98 cases of male,51 cases of women,average age 32.8±12.9 years),were randomly divided into two groups,One group includes 69 cases treated by adefovir combined with lamivudine.The other includes 80 cases just by adefovir.The genotype of the 149 cases were detected at the start of the ADV treatment.ALT normalization rate,HBV-DNA undetectable rate,HBeAg loss rate, HBeAg seroconversion rate and the detection rate of ADV resistance-associated gene were assessed during the following 12,24,48,72,96 weeks,respectively. Hepatitis B virus genotype and the quantity of hepatitis B virus were detected by the method of fluorescent PCR,We used the method of ntPCR-RFLP to detecte Adefovir dipivoxil resistance-associated mutations in hepatitis B virus The results showed that:The patients with HBeAg-positive chronic hepatitis B and lamivudine-resistant were treated by ADV or ADV+LAM,The HBV-DNA reduction and negative conversion rates of the group treated by ADV is lower than that of the group treated by ADV+LAM,Before the treatment of 72 weeks there was no significant difference(P＞0.05),By the treatment of 96 weeks,The HBV DNA negative conversion rate ADV monotherapy and combination therapy group were 65%and 81.2%,respectively.It was statistically significant difference(P＜0.05);ADV monotherapy group has lower ALT normalization rate than the ADV +LAM group,but there was no significant difference(P＞0.05) before 72 weeks, up to the treatment of 96 weeks the ALT normalization rate of ADV monotherapy group and combination therapy group was 76.3%and 89.9%,respectively.It was statistically significant difference(0.01＜P＜0.05);ADV monotherapy group has lower HBeAg negative conversion rate than the ADV+LAM group,there was no significant difference(P＞0.05) before 48 weeks,up to the treatment of 72 weeks the HBeAg negative conversion rate of ADV monotherapy group and combination therapy group was 8.8%and 20.3%,respectively,up to the treatment of 96 weeks the HBeAg negative conversion rate of ADV monotherapy group and combination therapy group was10%and 24.6%,It was statistically significant difference(P＜0.05);ADV monotherapy group has lower HBeAg seroconversion rate than the ADV+LAM group,there was no significant difference(P＞0.05) before 72 weeks, up to the treatment of 96 weeks the HBeAg seroconversion rate of ADV monotherapy group and combination therapy group was 6.3%and 18.8%, respectively.It was statistically significant difference(0.01＜P＜0.05); HBV-DNA negative conversion rate,HBeAg disappearance and ALT normalization rate has no significant difference between HBV genotype B and C Groups(P＞0.05),it can be seen that genotype B and genotype C of chronic hepatitis B has no relationship with the efficacy of adefovir dipivoxil.,Adefovir dipivoxil resistance rate of genotype C has been consistently higher than that of genotype B throughout the course of treatment,but P＞0.05.The patients with HBeAg-positive chronic hepatitis B and lamivudine-resistant were treated by ADV or ADV+LAM,The patients treated with adefovir monotherapy has higher risk and earlier time in the adefovir resistance variation than combined treatment with lamivudine and adefovir,up to the treatment of 72 weeks ADV resistance rates of ADV monotherapy group and United group were 13.8%and 2.9%(0.01＜P＜0.05),respectively,up to the treatment of 96 weeks ADV resistance rates of ADV monotherapy group and United group were 20%and 4.3%(P＜0.01), respectively.Whether switch to ADV monotherapy or ADV united LAM,If the virus in patients with low response rate when treatment for 48 weeks is apt to have ADV resistance in long-term medication.Especially,when treatment for 48 weeks serum HBV DNA load≥5 log10 copies/ml has higher risk of emergence of ADV resistance than the serum HBV DNA load of＜5 log10 copies/ml,and there is significant difference.The experiment evaluate the efficacy and resistance of adefovir dipivoxil about adefovir dipivoxil treatment of patients with HBeAg-positive chronic hepatitis B and lamivudine-resistant,evaluate the effects of treatment(adefovir dipivoxil monotherapy,adefovir dipivoxil combination lamivudine therapy)and genotype on the efficacy and the recurrence of adefovir dipivoxil resistance.The viral load of adefovir dipivoxil therapy to 48 weeks has close relationship with the occurrence of adefovir dipivoxil resistance.In conclusion,The long-term efficacy of Adefovir and Lamivudine combination therapy is better than that of Adefovir monotherapy in HBeAg(+) CHB patients and short-term efficacy is similar. Combination therapy has lower risk and later time of ADV resistance variation than the ADV monotherapy therapy,genotype B and C may be unrelated with ADV treatment efficacy.The ADV resistance rate of the patients with genotype C is above the patients with genotype B,but have no significant difference (P＞0.05).Both the adefovir dipivoxil monotherapy and combination therapy are likely to appear adefovir dipivoxil resistance in long-term treatment,but The incidence of ADV resistance is closely related with the serum HBV-DNA load of the 48th week. |
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