Comparative Analysis Of The Efficacy Of ETV With LAM Combined With ADV For The Treatment Of HBV-related Compensated Liver Cirrhosis

Objective:To compare the efficacy of combined lamivudine(LAM) and adefovir dipivoxil(ADV) therapy with that of entecavir(ETV) monotherapy for hepatitis B virus(HBV)-related compensated liver cirrhosis,which put forward the optimal treatment for patients with compensated HBV-related cirrhosis.Method:(1) 88 patients which visited the outpatient clinic in our hospital with HBV-related compensated liver cirrhosis from January 2012 to April 2014 are divided into two groups by clinicians and patients, one group(n = 65) receiving entecavir(ETV 0.5mg, qn) treatment( if viral breakthrough occurs which HBV DNA rise more than one pair of values from the lowest value or converted from negative to positive a month later with the same reagents retest to confirm in patients with good compliance and never change the treatment methods; proposes to change ETV to 1.0mg qn and add adefovir 10 mg qd antiretroviral therapy); the other group(n = 23) treated with combined LAM and ADV therapy(ADV 10 mg, LAM 100 mg, qd)( if viral breakthrough occurs recommended for treatment with tenofovir 600 mg qd).Both groups were followed for two years.(2) The follow-up time was 2 years.Detect the blood routine and biochem-ical parameters(7100 automatic analyzer, Hitachi Limited, Japan) once every 3months; detect the HBV DNA ration(plus a measurement at the third month)(One-step automated nucleic acid extraction instrument,one-step PCR, Sheng Xiang sansure biotech, Hunan Province, define the HBV DNA ration less than 100copies/ml as negative),blood coagulation,AFP(microsome chemilumines cenceme thod, Abbott, USA), liver ultrasound( LOGIQ9, GE, USA) and Fibroscan once every 6 months; detect hepatitis B five once every 12 months.(3) To compare the disease progression,HBV DNA negative rate,HBe Ag negative rate,HBe Ag seroconversion rate,Child-Pugh score, MELD score, liver stiffness values, ALT, ALB, TBIL, PTA and so on between the two groups before and after treatment.(4) Statistical analysis: Data analysis was performed using SPSS20.0.The data are firstly treated with normality and homogeneity of variance test; measurement data using normal distribution mean add and subtract standard deviation,comparison before and after the treatment of two groups using t-test and paired t test; counting data using percentage and compared with chi-square test, and Fisher’s exact test; Non-normal distribution using median(four point interval)(M(P25-P75))and Mann-Whitney U non-parametric test;(p<0.05) difference is statistically significant, p<0.01 indicating significant differences.Results:At 104 weeks 4 cases were lost, 5 end point events occurred in ETV group,56 patients were followed up to 104 weeks; LAM + ADV group, 5 cases lost,18 cases were followed up for 104 weeks. The reason of lost for patients is that they withdrew from the study automatically.1.The main index of the curative effect:the incidence of endpoint(decompensated cirrhosis and HCC+death) and the primary liver cancer1.1 At the 104 week the incidence of the endpoint in ETV and the combinati-on ADV with LAM group were 8.20%(5/61) and 0.00%(0/18), there was no statistically significant difference(P = 0.58).1.2 At the 104 week the incidence of the HCC in ETV and the combination ADV with LAM group were 4.92%(3/61) and 0.00%(0/18), there was no statistically significant difference(P = 1.00).2. Secondary outcome: the virology, serology, biochemical responses, liver hardness value, CTP and MELD score changes.2.1 Virological response:1 At the 104 week the incidence of HBV DNA negative rate(< 100copies/ml) in ETV and the combination ADV with LAM group were 89.29%(50/56), 94.44%(17/18), there was no statistically significant difference(P = 1.00).2 At the 104 week the incidence of virological breakthrough rate(HBV DNA rise from the lowest more than one value) in ETV and the combination ADV with LAM group were 1.79%(1/56), 5.56%(1/18), there was no statistically significant difference(P = 0.430).2.2 Serological response:At the 104 week the incidence of HBe Ag negative rate in ETV and the combination ADV with LAM group were 22.86%(8/35) and 22.22%(2/9)(P= 1.000); the HBe Ag seroconversion conversion rate were 11.43%(4/35) and22.22%(2/9)(P = 0.586); There was no statistically significant difference.2.3 Biochemical responses:At the 104 week the improvement of liver function such as ALT, ALB,TBIL and PTA in ETV and the combination ADV with LAM group was similar;there was no statistically significant difference(P >0.05).2.4 Hardness value of the liver(LSM) changes:At the 104 week the average of LSM in ETV group was 10.72 ±5.31Kpa: and LAM + ADV group was 8.71±2.86 Kpa;there was no statistically significant difference(P = 0.206).2.5 CTP and MELD score comparison:At the 104 week there was no statistically significant difference in ETV group and the combination ADV with LAM group about the Child-Pugh score(P = 0.551) and MELD score(P = 0.082).3. The liver function improvement compared to the baseline:At the 104 week the ALT, ALB, TBIL, PTA,Child-Pugh score and MELD score improved significantly than the baseline level, there was statistically significant difference(P < 0.05).Conclusions:Both Lamivudine plus adefovir combined therapy and entecavir monotherapy can effectively suppress viral replication and improve liver function, and both therapies can delay progression of the disease then to reduce mortality.All patients are well-tolerated with the drugs. But there was no significant difference between the two therapy programs; but study still needs further extended follow-up time, further expand the sample size to verify the findings.