| Objective:Discuss the clinical curative effect and safety in gene mutations patients with chronic viral hepatitis who switched to tenofovir disoproxil treatment alone;understanding the clinical efficacy of tenofovir disoproxil in different treatment resistant patients and hepatitis B virus DNA load.Methods:Patients with hepatitis B virus(HBV)infection in the First Affiliated Hospital of Zhejiang University medical school from 2012-9-1 to 2015-09-30 were collected,among them HBV genotype resistant chronic hepatitis B(CHB)patients were selected.According to the guidelines for prevention and treatment of chronic hepatitis B in China in 2010,a total of 33 cases of CHB gene resistant patients who meet the criterion were enrolled.Basic data were collected:the general population characteristics(age,gender),the type and dose treatment of nucleoside(acid)analogues(NAS)antiviral drug,confirmed resistant genotypes(Research Group will define this situation as the initial time)clinical manifestations,resistance gene a said and a number,initial blood examination situation hepatitis B virus e antigen(HBeAg),hepatitis B virus e antibody(HBeAb),HBV hepatitis virus DNA level(HBV DNA),alanine transfer enzyme(ALT),serum creatinine(SCr),urine protein,liver,gallbladder,spleen and color Doppler ultrasound examination investigation.Diagnosis of genotypic resistance,33 cases of genotype resistance patients received tenofovir(TDF)monotherapy,Subjects were followed up for 48 weeks.During follow-up,the clinical manifestations,blood examination(HBeAg and HBV DNA load,ALT,SCr),urine protein,liver,gallbladder,spleen and color ultrasound examination were collected after 12 weeks,24 weeks,36 weeks and 48 weeks.When retrospective analysis of 33 patients with single tenofovir antiviral therapy for 48 weeks,HBV DNA level,HBV DNA decreased levels and the cumulative decline level and HBV DNA non-detectable rate and at the end point(48 weeks),the ALT recovery rate,HBeAg serum conversion rate,virological response rate,virological breakthrough and incidence of adverse events were compared before and after the treatment at 12,24,36,48 weeks.Statistical analysis using Rank sum test and rank correlation analysis.Results:All of the 33 patients were lamivudine(LAM),adefovir dipivoxil(ADV),grace for entecavir(ETV),telbivudine(LDT)NAS antiviral drug treated patients,and exist a number of different gene loci(or)drug resistance(1?4),including:173L,180M,181V,181T,184L,184A,184F,202G,2041,204V).After follow-up,the data were analyzed statistically.Among them:(1)33 cases of patients at 12?48 weeks after treatment in TDF weeks were achieved complete virologic response,100%to achieve the conventional virus non-detected,(2)the clinical manifestations of 33 patients with initial liver function damage after TDF treatment were changed to comfortable,and the clinical manifestations were significantly improved.(3)18/21 cases were replaced by TDF alone after treatment ALT decreased to normal,the recovery rate of 85.71%;(4)7/25 cases of HBeAg were changed from positive to negative,negative rate was 28.00%,among them,4/25 cases of patients with HBeAg serum clearance,Clearance rate was 16.00%,3/25 cases of patients with HBeAg serum conversion,the conversion rate was 12%;(5)5/33 patients were treated by TDF alone,the liver morphology was changed from the original liver parenchymal inflammatory color ultrasound to normal liver parenchyma color ultrasound,the obvious improvement of liver inflammation,and the improvement rate was 15.15%;(6)the lower the initial DNA HBV load,the lower the early implementation of the virus can not be measured(rs=0.39,P=0.03),that is,the lower the initial viral load of CHB patients,the more likely to have a viral response;(7)Numbers of drug resistance gene and virological response time difference was statistically significant(rs=0.36,P=0.04);CHB patients with drug resistance gene loci,the more the longer virology unpredictable;(8)33 patients regularly monitoring serum creatinine levels,monitoring urine protein had no obvious abnormalities,including 2/33 cases of patients with TDF alone appeared moderately elevated serum creatinine,after 48 weeks after renal ultrasound further examination,has not been found apparently unusual,kidney hints kidney better security.Conclusion:1.TDF as a first-line antiviral treatment at CHB,in the case of LAM,ADV,LdT,ETV and other NAs genes resistant,can still inhibit DNA HBV replication,the recovery rate of ALT were high,and the multiple loci resistant patients also showed good antiviral effect;2.Most of the patients with 48 weeks use of TDF tolerance,security,all the better;3.TDF has a certain effect on renal function,it is recommended that regular monitoring of urine routine,renal function and other related indicators,and try to avoid share with renal toxicity of drugs. |
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