Types and emergence time of YMDD motif mutation in hepatitis B virus polymerase gene during lamivudine treatment / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the types and emergence time of YMDD motif mutation in hepatitis B virus (HBV) polymerase gene during lamivudine treatment.</p><p><b>METHODS</b>The serum samples were collected from 33 patients with HBV DNA rebounding and 2 non-responders after at least one year lamivudine treatment. HBV polymerase gene was amplificated by PCR, then the products were detected by restriction fragment length polymorphism (RFLP) and by direct sequence analysis.</p><p><b>RESULTS</b>The variants with YMDD mutation were 14 out of the 35 patients. Mutation patterns detected in these patients included four YIDD, six YVDD, three YI/VDD and one YI/MDD. The mean emergence time of YMDD variants was 11.07+/-3.65 months after the treatment, and the earliest one and the latest one occurred 5 months and 17 months after the treatment respectively. The emergence times of YIDD, YVDD, YI/VDD were (10.00 +/- 1.41) months, (11.67 +/- 4.41) months and (13.33 +/- 3.31) months respectively, which had no statistical significance (F = 0.543, P < 0.05). Three patients treated with lamivudine 200 mg every day after the mutation were followed up for 6 months, whose HBV variants had not vanished.</p><p><b>CONCLUSIONS</b>There are many kinds of HBV variants after lamivudine treatment, including YIDD, YVDD, YI/VDD and YI/MDD. The emergence time of variants is quite variable between different types and the mean time is (11.07 +/- 3.65) months after treatment, and there is no relationship between the type of YMDD mutation and the time of lamivudine administration.</p>

Distribution of lamivudine- resistant variants in hepatitis B virus / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To observe the distribution of HBV variants resistant to lamivudine and their relation to clinical manifestations of chronic hepatitis.</p><p><b>METHODS</b>Using direct sequencing, YMDD (tyrosine-methionine-aspartate-aspartate) variants in patients with chronic HBV were detected before and during treatment with lamivudine. A statistical analysis of the distribution of HBV strains resistant to lamivudine was performed.</p><p><b>RESULT</b>Four variant strains existed in patients before lamivudine treatment, 128 variant resistant strains were noted after 6 mouths of lamivudine treatment including 42 YVDD (valine) variants, 20 YIDD (isoleusine) variants and 66 non-YMDD variants. According to the hepatitis severity, 8 patients were mild, 108 moderate and 12 severe. Viral loading was higher and clinical types were more severe in no-YMDD variants.</p><p><b>CONCLUSION</b>Variant strains including strains resistant to lamivudine exist naturally before lamivudine treatment, but lamivudine-resistant ones become more dominant after treatment. Liver inflammation is more severe in non-YMDD group.</p>

Preliminary observation on the efficiency and safety of Lamivudine used in decompensative hepatic cirrhosis (B) accompanied by hypersplenism / 浙江大学学报·医学版

OBJECTIVE: To study the efficacy and safety in patients with decompensative hepatic cirrhosis treated with Lamivudine. METHODS: Eighteen decompensative hepatic cirrhosis (B) (active phage) patients accompanied with hypeersplenism were treated with Lamivudine 100mg po. per day. The total course of treatment was 3 months to 6 months when HBVDNA became negative and HBeAg seroconversion occurred in these patients after Lamivudine treatment. The efficacy and safety in patients were evaluated as follows: HBVDNA were negative, HBeAg seroconversion occurred and hepatic cirrhosis child-stageing changed. The efficacy and safety between treated group and contrast group were compared during treatment with Lamifudine for 1 year and follow-up foe 1 year after completing treatment. RESULTS: The total efficacy of treated group was 27.7% and 71.43% respectively during the phase II trial and the safety was good in these patients. CONCLUSION: The efficacy and safety of Lamivudine are good while it is used in non-registered adaptation of decompensative hepatic cirrhosis with hypersplenism.