| Objective: In this study,we collected various cases of chronic hepatitis B treated with nucleoside(acid)analogues in Shijiazhuang area,analyzed the genotype and mutation status of hepatitis B virus resistance mutations in vivo,and treated with LAM or LAM in combination with ADV.The aim of this study was provide a scientific basis for improve the effect of chronic hepatitis b liver treatment.Methods:1 Experimental research objectChronic hepatitis b virus infection patients were derived from the fifth hospital of Shijiazhuang City,who were treated in October 2011-March 2016.The diagnostic criteria were based on the <Guidelines for the prevention and treatment of chronic hepatitis B(2010 Edition)> which were made by Chinese Society of Hepatology and Chinese Society of Infectious Diseases.The patients were all treated with nucleoside analogues.2 The study object groupsThe hepatitis B resistance gene sequencing,ALT,AST,HBV-DNA quantification and hepatitis B detection were carried out.The patients who were initially treated as LAM are divided into three groups: The first group(NO.1 group),after LAM resistance occurred,they changed the therapeutic schedule by using LAM combined with ADV treatment;And the second group(NO.2 group),when the resistance occurred,they use ETV with ADV for treatment;And the third group(NO.3 group),use ETV treatment.In addition,the chronic hepatitis B patients who were treated by LAM combined with ADV were divided into two groups: first group(NO.1 group),changed by using ETV treatment;And the second group(NO 2 group),for 15 cases,use ETV combined with ADV for treatment.3 Blood and genetic testingThe levels of ALT,AST and HBV-DNA were detected at 3 months,6months and 12 months after treatment in each group.Hepatitis B virus resistance gene was detected by gene sequencing.ALT and AST were detected by 7600 automatic biochemical analyzer.HBV DNA was detected by fluorescence.Quantitative PCR.Hepatitis B was detected by ELISA.4 Data analysisSPSS21.0 software was used for statistical analysis.Metrological data were used to check the normal distribution,and the t-test was used to compare the normal distribution data.The non-normal distribution data were used to describe the median,and the rank sum test was used.HBV DNA were taken logarithm calculation;to P <0.05 for the difference was statistically significant.Results:1 HBV-P mutation locus and mutation rateThe base sequence of 14 loci in P region of hepatitis B virus infected by454 hepatitis B patients in Shijiazhuang area was analyzed.Among them,437 cases had mutations in gene locus,the mutation rate of total gene was 96.3%.The mutation rates of the 14 loci detected were M204 I / V / S 64.3%(292/454),L180 M 38.8%(176/454),A181 V / T / S 22.7%(103/454),V173 L locus 9.9 %(45/454),N236 T locus 9.3%(42/454),V207 I / L / G locus 8.8%(40/454),S213 T site 7.0%(32/454),V214 A site 5.3% 24/454),M250 V / L locus 4.4%(20/454),S202 G / I locus 4.4%(20/454),N / H238 T / D site 4.0%(18/454),T184 A / G / I / S site 3.5%(16/454),P237 H locus 2.6%(12/454),Q215 S locus 1.5%(7/454).2 The HBV DNA load changes of the LAM-resistant hepatitis B patients with different rescue regimensThe load of the third month,the 6th month and the 12 th month after changing the medical plan were significantly decreased compared with those before.It occurred in all these three groups of LAM drug resistance hepatitis B patients.P<0.05,the difference were statistically significant.The ALT valuesof the three groups were significantly lower than those before changing the eatment program,P<0.05,the difference was statistically significant.The AST values of LAM combined with ADV program were significantly decreased compared with those before changing the treatment program,P<0.05,the difference was statistically significant.And the difference between AST value of ETV and ETV combined with ADV program and the value before changing the treatment program was not significant.P> 0.05,there were not statistically significant.3 The clinical results of LAM combined with ADV resistant hepatitis B patients with different rescue programsThe HBV DNA load of the third month,the 6th month and the 12 th month after changing the medical plan were significantly decreased compared with those before.It occurred in all these three groups of LAM combined ADV resistance hepatitis B patients.P<0.05,the difference Were statistically significant.The ALT and AST of ETV program were decreased compared with those before changing the treatment program,but there was no significant difference compared with that before changing the treatment program,P> 0.05,the difference was not statistically significant;for ETV combined with ADV program the value of ALT,AST had significantly decreased compared with that before changing the treatment program,P<0.05,the difference was statistically significanConclusion:1 The detection rate of M204I/V/S,L180 M and A181V/T/S mutations in the main mutations of HBV P in the Shijiazhuang area was 64.3%(292/454),38.8%(176/454)and 22.7%(103/454).Resistance mutations mainly correspond to LAM and ADV resistance.2 When the drug resistance appeared in the hepatitis B patients who initially use LAM to tread the illness,they changed the therapeutic schedule.compared with those who using ETV or ETV combined ADV scheme,the patients using a combined LAM,ADV plan not only more effectively inhibit viral replication,more effectively to liver function return to normal,and cansave treatment costs.3 When the drug resistance appeared in the hepatitis B patients who initially use LAM to tread the illness,they changed the therapeutic schedule by using ETV combined ADV scheme.The comprehensive curative effect is obviously better than that of ETV monotherapy. |
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