Tenofovir Dipivoxil In The Treatment Of Chinese Patients With Drug-resistant Chronic Hepatitis B

Objective:Discuss the clinical efficiency and safety in gene mutations patients with chronic viral hepatitis B who switched to tenofovir disoproxil treatment.Methods1.Clinical evaluationInclusion criteria and exclusion criteriais are based on The Chronic Hepatitis B prevention Guide（2015 edition）drawn up by The Chinese Liver Association and The Chinese Medical Association.The test scheme and sample size are designed according to the non-inferior-effect principle.The 65 cases of CHB with other nucleoside resistance in a municipal hospital from Oct.2015 to May 2016 can be divided at random into TDF group and the combined group.The TDF group is given TDF300mg/day.After 48 weeks’treatment cycle and once 12 weeks’observation,the contrast analysis is made of HBV DNA ration level（real time PCR method）,a drop of HBV DNA（the difference between HBV DNA quantitative level at this time and the baseline quantitative level）,HBV response rates（the ratio of virological number and total treatments）,HBe Ag overcast rate（electrochemical luminescence quantitative analysis）,ALT and total bilirubin（automatic biochemical analyzer）etc.SPSS17.0 software is adopted.2.Safety evaluationSafety evaluation includes subjective adverse events assessmentandlabevaluation.Thesubjectiveadversereactionscover headache,vomiting,syncope,insomnia,fatigue,joint pain,etc.The lab evaluations cover serum creatinine,blood phosphorus,blood calcium,urea nitrogen and urine protein detection（automatic biochemical analyzer）.Results1.Clinical evaluation 27 cases of TDF group and 31 cases of the combined group are formed at random.7 cases are shed.（1）In general.The average age of TDF group is49.27±7.64 and the combined group 50.91±8.52.The ration level of TDF group is6.12±1.15log₁₀copies/ml and the combined group 6.31±1.02log₁₀0 copies/ml.The ALT abnormal rate of TDF group is 59.26%and the combined group 61.29%.The patients with HBeAg positive in TDF group is 15 and 22 in the combined group.There’s no difference between the two groups（p>0.05）.（2）The results of HBV DNA quantitative level.In 12^th,24^th,36^thand 48^thweek after change,the quantitative level of TDF group is3.72±0.82log₁₀copies/ml,2.35±0.91log₁₀copies/ml,2.21±0.81log₁₀copies/mland2.13±0.47 log₁₀copies/ml.Compared with the baseline,there is some difference（p<0.05）showing that the effectiveness in TDF group comes up in 12^thh week,goes up to a peak and keeps steady in 24^thweek.The combined group 5.87±0.99log₁₀copies/ml,3.78±1.16log₁₀copies/ml,3.49±1.12log₁₀copies/mland3.32±0.97log₁₀copies/ml,Compared with the baseline in 24^th,36^thand 48^thweek,there is some difference showing that the effectiveness in the combined group comes up and goes stable in 24^thh week.Obviously TDF turns effective earlier.（3）The results of HBV DNA reduction.In 12^th,24^th,36^thh and 48^thh week after change,The TDF group is 2.40±0.98 log₁₀copies/ml,3.77±1.07log₁₀copies/ml,3.91±1.13 log₁₀copies/ml and 4.01±1.14 log₁₀copies/ml.Compared with baseline in 24^thh and 12^thh week,there’s some difference（p<0.05）.TDF becomes most effective and goes stable in 24^thweek.The combined group is0.44±0.58log₁₀copies/ml,2.53±0.67log₁₀copies/ml,2.82±0.79log₁₀copies/mland2.99±0.78log₁₀copies/ml.The comparison between two groups shows that the virus in TDF group obviously declines much more than the combined group and TDF inhibits the virus much more effectively.（4）The results of virologicalresponse rate.In 12^th,24^th,36^thh and 48^thh week after change,the virological response rate of TDF group is 44.44%,62.96%,77.78%and 81.48%.compared with the baseline,there’s some difference（p<0.05）.In 12^thh week,TDF starts to respond and reaches 81.48%in 48^thh week.The combined group is 3.23%,16.13%,19.35%and 25.81%.Compared with baseline in36^thh and 48^thh week,there’s some difference.The response starts in 36^thh week and continues to be stable.The comparison between the groups shows that the response rate on TDF group is much higher than that in the combined group,ie.the proportion of patients with CHB in TDF group is much higher.In 48^thweek,the virologicalresponse rate of HBeAg positive patients is 66.67%.HBeAg negative patients 100%.（5）The results of the conversion rate.Among 37 cases of HBeAg positive,2 cases in TDF group and 3cases in the combined group are conversed in 48^thh week.（6）The results of ALT repetition rate.In 12^th,24^th,36^thand 48^thweek after change,the rate for TDF group is 56.25%,81.25%,87.50%and 93.75%.Compared with the baseline,there’s some difference.TDF turns effective to liver function in 12^thweek,gets maximum and goes stable.The rate for combined group is 36.84%,47.37%,57.89%and 57.89%.Compared with the baseline,there’s some difference.The effectiveness comes up and goes stable.There’s some difference between the two groups in 24^thh week.With the extension of treatment,the TDF group is better than the combined group.（7）The results of bilirubin.In 48^thweek,the bilirubin is16.7±5.1umol/L for TDF group and 18.6±6.0 umol/L for the combined group.（8）The results of Hepatic B hyper recovery.In 48^thweek,5 cases in TDF group change from the inflammatory liver parenchyma to the normal liver parenchyma,but one only in the combined group.2.Safety evaluationTwo cases with one in each group shows subjective symptoms of fatigue,dizziness,nausea etc.There’s no difference in the serum creatinine,blood phosphorus,blood calcium,urea nitrogen and urine protein before and after lab test.Conclusion1.TDF 300mg/day used alone for 48 weeks has strong antiviral effect,treats the patients with CHB resistance effectively in China,reduces HBV DNA level and improve liver function.2.After the continuous drug use for 48 weeks,there’s no adverse reaction in the patients treated with single drugs and combined drugs.