| Objective: To explore nucleoside (acid) analogue's anti-viral effect on the lamivudine-resistant patients with chronic hepatitis B, for further follow-up treatment for patients with lamivudine-resistant. Methods: 181 cases in department of gastrointestinal medicine in Jilin University Sino-Japanese Friendship Hospital identified as lamivudine-resistant chronic hepatitis B patients were randomly divided into two groups.One group include 97 cases treated by adefovir combined with lamivudine. The other include 84 cases just by TU entecavir . To observe and discuss anti-virus effect, the 24-week response to the situation and long-term efficacy and resistance status of the virus. Results: analysis of the effect on chronic hepatitis B patients with lamivudine-resistant treated by lamivudine combined adefovir or TU entecavir alone: The results showed that, in HBeAg-positive patients used by adefovir combined with lamivudine, 12 weeks and 24 weeks ALT normalization rate were 12.1% and 42.4%, significantly less than those in entecavir treatment Group which were 71.9% and 73.7% .In HBeAg-negative patients used Adefovir combined with lamivudine ,12 weeks and 24 weeks ALT normalization rate were 12.9% and 32.3%, significantly less than those in entecavir treatment Group which were 59.3% and 74.1%. With time going on, ALT normalization rate and HBV DNA conversion rates continue to rise. In HBeAg-positive patients of two groups 96 weeks ALT normalization rate were 89.4% and 84.2%; in HBeAg-negative patients of two groups 96 weeks ALT normalization rate were 90.3% and 85.2%. There was no significant difference between the two groups (P> 0.05); analyse HBV DNA decline of the situation and unpredictable rate. The results showed that for HBeAg-positive patients used by adefovir combined with lamivudine therapy group in 12 weeks and 24 weeks, HBV DNA loas was from baseline load 5.4±0.906 copies / ml down to 5.15±0.529 copies / ml and 4.16±0.419 copies / ml. And HBV DNA unpredictable rate was down to 12.1% and 40.9%. For HBeAg-negative patients, HBV DNA load from baseline load 5.6±0.807copies/ml down to 5.25±0.538 copies / ml and 4.21±0.421 copies / ml. And HBV DNA unpredictable rate was down to 9.7 % and 29 %. HBV DNA load and unpredictable decline were significantly lower than entecavir treatment group in 12 weeks and 24 weeks, for HBeAg-positive patients, HBV DNA load was from baseline load 5.7±0.776copies/ml were down to 3.82±0.512copies/ml and 2.52±0.443copies/ml. For HBeAg-negative patients , HBV DNA load was from baseline load 5.2±0.854copies/ml down to 3.92±0.556copies/ml and 3.22±0.473copies/ml.And HBV DNA unpredictable rate were 28.2% and 56.3% (P both <0.05). With the extension of treatment, HBV DNA load in the two groups continued to decline, and HBV DNA unpredictable rate continued to rise, in 96th week the patients with HBeAg-positive in two groups HBV DNA load dropped separately to 2.13±0.417copies/ml and 2.26±0.406copies / ml. HBV DNA unpredictable rate was 80.3% and 78.9%, HBV DNA load of HBeAg-negative patients dropped separately to 2.32±0.407copies/ml and 2.36±0.404copies/ml. HBV DNA unpredictable rate were 80.3% and 78.9% . HBV DNA conversion rates were 80.7% and 78.5%, there was no significant difference between the two groups (P> 0.05). In different periods, between the two groups the HBeAg loss rates and HBeAg serum conversion rates were not significantly different. For Adefovir combined with lamivudine therapy groups, HBsAg elimination coefficient was 2.1 percent in the 96th week. For TU entecavir therapy group, HBsAg didn't disappear in the 96th week. In both two groups, there were no HBsAg / HBsAb serum conversion. Analyze the anti-viral effect on the 181 cases in the 48th,72nd and 96th week ,the result showed that in the 24th week HBV DNA load in serum of some patients could be controlled under 3 log10 copies / ml whose HBV DNA unpredictable rate and ALT normalization rate were all 100 %; HBeAg loss rates were 29.9%, 37.3% and 44.8%; HBeAg serum conversion rate was separately 19.4%, 28.4% and 32.8% in the 48th ,72nd and 96th week. In 24th week HBV DNA load in serum of some patients were controlled between 3 log10 copies / ml and 5 log10 copies / ml whose 44.6%, 63.5% and 70.2%, ALT normalization rate were 51.3%, 75.6% and 85.1%; HBeAg loss rates were 2.1%, 4.2% and 8.4%; HBeAg serum conversion rates were 0%, 2.1% and 4.2%. Another patients were tested HBV DNA load≥5 log10 copies / ml in the 24th week ,whose HBV DNA unpredictable rates were all 0%; ALT normalization rate were separately 6.7%,13.3% and 20%; HBeAg loss rates and serological conversion were all 0% in the 48th ,72nd and 96th week. HBV DNA unpredictable rate, ALT normalization rate, HBeAg loss rate and serum conversion rate of the patients with HBV DNA load <3 log10 copies / ml and HBV DNA load between 3 log10 copies / ml ~ 5 log10 copies / ml in 24th week were significantly higher than those with load≥5 log10 copies / ml in the 48th,72nd and 96th week. 2.2% of patients with HBV DNA load <3 log10 copies / ml in the 24th week were discovered HBsAg disappeared in the 96th week. None of the patients with HBV DNA load between 3 log10 copies / ml ~ 5 log10 copies / ml and≥5 log10 copies / ml were discovered HBsAg disappeared in the 96th week . Investigate the in both two groups, results showed in TU entecavir therapy group the virus rebound rate were separately 0%, 1.2% and 4.8% in the 48th ,72nd and 96th week ,while in the adefovir combined with lamivudine the virus rebound rate was 1.0% starting in the 96th week. Analyze the relation between HBV DNA load in the 24th week and virus rebound rate in both groups, results showed adefovir combined with lamivudine therapy group with HBV DNA Load <3 log10 copies / ml and 3 ~ 5log10 copies / ml did not discover virus rebound; on the other hand, the patients in adefovir combined with lamivudine therapy group with HBV DNA load≥5 log10 copies / ml discover virus rebound in the 96th week and the virus rebound was 12.5%. Entecavir therapy group with HBV DNA Load <3 log10 copies / ml and 3 ~ 5log10 copies / ml did not discover virus rebound in the 48th,72nd and 96th week; the patients in Entecavir therapy group with HBV DNA load≥5 log10 copies / ml discover virus rebound and the virus rebound rate were separately 0%, 16.7% and 33.3% in the 48th,72nd and 96th week. Virus-resisitence rate of the patients with HBV DNA Load <3 log10 copies / ml and 3 ~ 5log10 copies / ml was significantly in the 24th week lower than that of the patients with HBV DNA load≥5 log10 copies / ml(p<0.05).Conclusion: lamivudine-resistant patients with chronic hepatitis B to switch to adefovir combined with lamivudine or ex-drug entecavir single agent doubling dose (1.0 mg) to continue anti-viral treatment, may get better treatment Effect. different nucleoside (acid) analogue long-term treatment on chronic hepatitis B patients with lamivudine-resistant the long-term efficacy and treatment of 24 week's HBV DNA load have closely related. Early results of the analysis, anti-virus treatment to predict the long-term effect. Regardless of adefovir and lamivudine combination, or a TU entecavir to redouble their separate programme, in the treatment of lamivudine-resistant virus are 96 weeks after a rebound phenomenon, the incidence of rebound phenomenon and the effect of 24 weeks anti-virus Closely related. |
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