| Background and ObjectiveThe chronic hepatitis B has a high incidence rate in China and the world. It is caused by the hepatitis B virus infection. According to the statistics, China has about93million people who have been infected by HBV,20million people are in chronic infection. HBeAg positive chronic hepatitis B is a kind of active disease status, it increases the risk of cirrhosis and primary liver cancer progress. The goal of the CHB treatment is to reduce HBV as curable as possible, prevent the occurrence of liver cirrhosis, liver failure and liver cancer. At present, the main drugs in the treatment of CHB are interferon and nucleoside (acid) analogue. Interferon has a short treatment course, it can effectively suppress HBV replication, have a higher HBeAg serum conversion rate, however, its adverse reaction such as flu-like symptoms, hair loss and relative strict indications, contraindications, limit its clinical application to some extent. Nucleoside (acid) analogue has the characteristic such as easy taking, no obvious adverse reactions and so on, it has been widely used in clinical anti-HBV therapy. But the long-term medication prone to viral resistance, once the drug resistance, the antiviral effect is greatly reduced, virus rebound also could make the condition worse. So the search for more potent inhibition of viral replication, low resistance rate and long-term safety of the drug is the hot spot of drug research.Tenofovir disoproxil fumarate (TDF) is a new kind of nucleoside (acid) reverse transcriptase inhibitors, in2001and2008, the FDA has its approval for the treatment of HIV and adult CHB. Besides, more than30countries and regions also approved the TDF indications for the treatment of CHB. The TDF III stage of clinical trials for CHB in China has been finished and TDF gets its approval for the treatment of CHB, Its appearance has brought new hope for patients. The NAs roadmap concept refers to optimizing treatment according to the HBVDNA levels at week24, in order to improve the long-term curative effect and reduce the occurrence of drug resistance. For LDT roadmap therapy, if w24HBVDNA load>1000copies/ml, the other nucleoside analogues (ADV for this study) was added in the antiviral therapy. The purpose of this study was to evaluate the efficacy and safety of tenofovir and LDT roadmap therapy on the treatment of HBeAg positive chronic hepatitis B, furthermore, provide the reference for clinical application.MethodsA total of50patients with HBeAg positive CHB who met the criteria were enrolled in the study. According to the proportion of1:1, they were randomly divided into group TDF (group A) and group LDT (group B) for48weeks of antiviral treatment. Group A was orally given TDF300mg/day, if HBVDNA breakthrough was observed, then ETV was switched to subsequent antiviral treatment. According to the randomized principle, group B was divided into group B1(14cases) and group B2(11cases). Group B1was orally given LDT600mg/day, if HBVDNA breakthrough was observed, the ADV10mg/day was added to antiviral therapy for48weeks. Group B2was given LDT for24weeks, if the w24HBVDNA>1000copies/ml, the ADV was added to antiviral therapy. The other patients were given LDT, then ADV was added until the HBVDNA breakthrough. HBVDNA, liver and kidney function, HBV markers, blood routine, urine routine, coagulation, the biochemical indicators and B ultrasonic were detected at baseline, week4, week12, week24, w36and week48respectively. If HBVDNA breakthrough was observed, the HBV drug resistance was analyzed. The patients’ adverse reactions were also closely observed. SPSS17.0statistical software was used for data process, the measurement data was compared by t test, the rate was compared by chi-square test, P<0.05was considered statistically significant.Results The25patients of group TDF were given TDF for48weeks. The25patients of group LDT were given LDT for previous24weeks. There were2patients of group B1were added ADV at w36for HBVDNA breakthrough. At w24, there were7patients of group B2were added ADV,while the other4cases were given LDT. So during w24and w48, there were16cases for group single LDT, and7cases for group LDT roadmap therapy. The main observation index results were as follows:1. Virological response:At w24, the HBVDNA levels in group TDF declined from8.71±0.41to2.12±0.84, while the group LDT declined from8.86±0.86to3.05±0.99, the HBVDNA levels in group TDF were significantly lower than that in group LDT (t=3.57, P<0.01). At w48, the HBVDNA negative conversion rates of group TDF, group single LDT and group LDT roadmap therapy were80.0%,68.9%and85.7%respectively, there were no statistically significant difference between the three groups (X2=1.05. P>0.05).2. ALT response:At w24, the ALT levels in group TDF declined from243.4±147.1to34.0±11.9, while the group LDT declined from198.0±118.9to42.0±12.7, the ALT levels in group TDF were significantly lower than that in group LDT (t=2.30. P<0.05). At w48, the ALT normalization rates of group TDF, group single LDT and group LDT roadmap therapy were84.0%,75.0%and85.7%respectively, there were no statistically significant difference between the three groups (X2=0.63. P>0.05).3. Serological response:At w48, the HBeAg negative conversion rates and HBeAg serological conversion rates in group TDF, group single LDT and group LDT roadmap therapy were32.0%,25.0%,28.6and24.0%,18.8,28.6respectively, there were no statistically significance between the three groups (X2=0.23,0.30. P>0,05).4. Drug resistance:in this study, HBVDNA rebound was not observed in group TDF and group LDT roadmap therapy, but there were2cases (12.5%) in group single LDT having HBVDNA rebound, there were no statistically significant difference between the three groups (X2=4.57.P>0.05). After HBV gene analysis, the2cases were rtM204I resistance, they were added ADV for antiviral treatment.5. Adverse reactions:all patients have no serious adverse reactions. Conclusion1. Tenofovir can effectively suppress HBV replication and improve liver function than LDT in a short time. After long-term application, TDF, LDT, and LDT roadmap therapy have no obvious difference on the ability to inhibit viral replication, and have good security.2. LDT roadmap therapy can obtain a good antiviral effect, and have no drug resistance.3. LDT has a high resistance rate, TDF may be superior to LDT in drug resistance.4. ADV is added to patients with LDT resistance for united antiviral therapy is a good choice. |
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