| Aims Antiviral therapy is the key measure to delay the progression of disease in patients with HBV-related cirrhosis, and adherence is the premise of obtaining good therapeutic effect. Based on real-word clinical data, we firstly evaluated the adherence to antiviral therapy of patients with HBV-related cirrhosis and explored the factors influencing the adherence of these patients, which could help clinicians recognize patients with non-adherence, and then in order to provid more evidence for clinicians to identify the factors that affect the outcomes of antiviral therapy, the influence of adherence to antiviral therapy on the treatment outcomes was analyzed.Methods Demographic characteristics(including patients’ ID, birth date, gender), routine biochemical and virological detection data and antiviral prescription information(including prescription date and the name, dose and usage of drugs) of patients with HBVrelated cirrhosis who were referred to Beijing You’an Hospital during Feb 14, 2008 and Dec 31, 2012 were collected from the hospital’s electronic database. Based on the above information, this study is divided into two parts as follows: Part I. Factors associated with adherence to antiviral therapy in patients with HBV-related cirrhosis: according to the patients’ antiviral dispensary records, we used the medication possession rate to evaluate the level of adherence to antiviral treatment of patients with HBV-related cirrhosis. Multivariate logistic regression was used to analyse the factors affecting the good adherence. Part II. The impact of adherence to antiviral therapy on the treatment outcomes in patients with HBV-related cirrhosis: Based on the first part study, we used survival analysis methods to compare the HBV DNA response rate, HBe Ag sero conversion rate, virological breakthrough rate among the patients treated with ADV or ETV with different medication adherence, respectively.COX regression was used to explore the impact of the medication adherence on HBV DNA response, HBe Ag seroconversion, virological breakthrough and the difference of treatment outcome between ADV and ETV through adjusting baseline characteristics and the factors that may influence the treatment effect.The χ2test was used to compare the rate of changing the therapeutic regimen and ALB normalization rate between different medication adherence.Results Part I. 1. Two hundred and ninty nine patients treated with ADV or ETV were included in Beijing area. The mean age was 51.6 years old(SD, 10.6), of whom, 117 patients with HBe Ag positive and 182 patients with HBe Ag negative. The male patients accounted for 65.9%. The median duration of follow-up was 585 days. The baseline log10 DNA copies/ml level was 5.5(SD, 1.4), and the median MPR was 93.7%(72.8%-100%). MPR is greater than or equal to 80% in most patients, accounting for 68%; the patients whose MPR is greater than or equal to 90% accounted for 45%; the patients whose MPR is equal to 100% accounted for 26.1% and the patients whose MPR < 50% only accounted for 12%. 2. Multivariate logistic regression was used to explore the factors associated with good adherence. Univariate analysis revealed that the medication adherence showed positive correlation with baseline ALB ≥ 35 g /L(OR=2.27,95% CI:1.425-3.618), baseline CHE≥4000 U/L(OR=2.601, 95% CI:1.617-4.183); and negative correlation with the longer treatment time(OR=0.549, 95% CI:0.389-0.757). It was showed that only treatment time had significant association with medication adherence(OR=0.021, 95% CI: 0.005-0.088) through multivariate analysis.Part II. 1. According to the HBe Ag status, patients were divided into HBe Ag positive and HBe Ag negative, the baseline characteristics was compared between patients treated with ADV or ETV. The results showed that baseline serum HBV DNA level was significantly higher in patients treated with ETV(P < 0.05); Thepatients treated with ADV had longer duration of treatment(P < 0.05). In addition, in the patients with HBe Ag(+), baseline ALT levels was higher in patients treated with ETV(P = 0.026). MPR of two groups of patients were about 94%(P < 0.05);There were no significant differences between the two groups in other liver function indexes. 2. The results of comparative effectiveness analysis of ADV and ETV showed that, in patients with HBe Ag(+),ETV demonstrated higher HBV DNA response rate than ADV(P = 0.001), The HBV DNA response rate of ETV and ADV at the 6, 12 and 24 month were 71.4%vs.50%, 89.0% vs.64.8% and 97.8% vs.77.6%, respectively, and that of patients with HBe Ag(-) were 81.5% vs. 68.4%, 93.8% vs.80.4% and 96.3%vs.92.8%, respectively(P = 0.003). After adjusting for covariates, patients with ETV would still achieve higher HBV DNA response with the hazard ratio(HR) of 1.880(1.191-2.959) and 1.787(1278-2.498) for HBe Ag positive and HBe Ag negative patients, respectively; In patients with HBe Ag(+), the virological breakthrough rate of ADV was lower than that of ETV with HR of 0.242(0.079-0.747); The rate of changing therapeutic regimen of ADV was 23.9% higher than ETV(P=0.0220). In patients with HBe Ag(+), the virological breakthrough rate of ETV was lower with HR of 0.268(0.092-0.777).The rate of changing therapeutic regimen of ADV was 27.7% higher than ETV(P < 0.001). There was no significant difference between the two drugs in HBe Ag serological conversion rate(P=0.7747).3. According to the medication adherence, patients were stratified to explore the effects of different adherence on treatment outcomes.The results showed that, for patients with HBe Ag(+),the HBV DNA response rates at 6, 12 and 18 month of ADV treated patients with MPR ≥ 95% were 37.3%, 28.4%, and 9.9% significantly higher than those with MPR<95%,respectively(P = 0.0037); for those patients treated with ETV, however, no significant difference was observed among patients with different adherence(P=0.2235). The rate of virological breakthrough of ADV with MPR<95% at 6, 12 and 24 month after virological response was 15.8%, 27.0% and 34.3%, respectively. However,in patients with MPR ≥ 95% had no virological breakthrough(P=0.2876); for those patients treated with ETV, the rate of virological breakthrough in patients with MPR < 95% was 18.7%, 27.6% and 31.2%, respectively. Which was 15.7%, 24.6% and 28.2% higher than patients with MPR ≥95%,respectively(P=0.0238). 4. For HBe Ag(+) patients treated with ADV,the HBV DNA response rates at 6, 12 and 18 month with MPR≥95% were 24%, 14.5% and 10.8% respectively higher than those with MPR<95%,but the difference was not statistically significant(P=0.0714). The HBV DNA response rate of patients treated with ETV after 12 month tended to be stable, but at 6, 9 month of therapy, the HBV DNA response rate of patients with MPR ≥95% were 15.1%, 10.0%, higher than patients with MPR < 95% respectively(P=0.0447). In addition, The rate of virological breakthrough of ADV with MPR<95% at 6, 12 and 24 month after virological response was 2.9%, 20.1% and 27.8%, respectively. Which were 0%, 9.4% and 17.2% higher than patients with MPR ≥95%,respectively(P=0.2147). for those with ETV, the rate of virological breakthrough in patients with MPR < 95% was 6.1%, 10.5% and 14.7%, respectively. Which was 6.1%, 10.5% and 11.2% higher than patients with MPR ≥95%,respectively. but the difference was not statistically significant(P=0.0616). 5. After Cox regression adjusting for baseline characteristics, the results showed that, for HBe Ag(+) patients, the rate of HBV DNA response of ADV with MPR ≥95% is greater than that of patients with MPR < 90%, and the HR was 4.35(1.711-11.062). The rate of virological breakthrough was lower than that of patients with MPR < 90%, and the HR was 0.013(0.000-0.889). for patients treated with ETV, there was no statistical difference between different MPR groups for the rate of virological response. The rate of virological breakthrough of patients with MPR≥ 95% was lower than that of patients with MPR<95%, the HR was 0.145(0.029-0.720). for patients with HBe Ag(-),the rate of virological response of ADV treated patients with MPR≥95% was 1.95 times higher than that of MPR<95% patients(95% CI:1.133-3.374) and the rate of virological breakthrough of that was 0.272 times of patients with MPR < 95%(95% CI:0.067-1.100). for those patients treated with ETV,the group of MPR≥95% was lower than that of patients with MPR<95%, the HR was 0.197(0.022-1.733), but the difference was no statistical significance(P = 0.143). Through comparing the rate of HBe Ag seroconversion and changing therapeutic regimen among patients with different adherence it was showed that, although, patients with good compliance had higher rate of serological conversion, lower rate of changing therapeutic regimen than that of patients with poor adherence, but these differences were not statistically significant.Conclusions 1. Compared to other chronic diseases, the level of adherence to antiviral therapy of patients with HBV-related cirrhosis was not lower. Patients with longer time of treatment tended to be nonadherence. 2. Compared with ETV, in order to achieve viralogical response, patients treated with ADV were more dependent on good adherence to antiviral therapy, which had a significant effect on viralogical response. Patients with poor adherence were more likely to have viralogical breakthrough, but poor adherence was not an independent predictor of HBe Ag serological conversion and changing therapeutic regimen. 3. The patients treated with ETV compared with that treated with ADV treatment could obtain earlier and higher rate of HBV DNA response and had lower rate of virological breakthrough and changing therapeutic regimen. The differences of HBe Ag serological conversion between two drugs were not significant. |
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