Researches from Pao-Chien Hospital Reports on Finding in Chronic Hepatitis B Virus Treatment with Nucleos(t)ide Analogue

Background and Aims: chronic infection with hepatitis B virus (HBV) is a major public health problem worldwide. Potential effective direct antivirus agents such as nucleos(t)ide analogues and the accumulation of substantial experience in the use of these drugs have lead to better therapeutic strategies for chronic HBV infection. The significance of HBV-DNA suppression in predicting long term outcome needs further investigation. Methods: Retrospective study of 139 participants with HBeAg-positive or negative, cirrhosis or none cirrhosis, we determined the rates of HBV-DNA undetectablity, ALT normalization, HBeAg seroconversion, HBsAg loss, reduction of HBV-DNA levels, virus breakthrough, relapse, and occurrence of hepatocellular carcinoma for treatment naive or retreatment on various nucleos(t)ide analogues for 3 years. The significances of predictive values of baseline factors and easy on-treatment virological and biochemical response have been analyzed. We also employed multivariate analyses to strengthen the positive predictive factors and identify optimal patients who would benefit more from the treatment. Results: A total 139 adult patients with a median age of 52.6(30-84) had proportion with male sex (79.9%), cirrhosis (36%), HBeAg-negative (69.8%), treatment naive (85.6%). Overall, 97 patients were treated with Entecavir therapy, 23 with Tenofovir, 16 with Telbivuldine, and 3 with Lamivudine. Overall, the HBV-DNA undetectability at 1 year was 69.1%, the ALT normalization at 1 year was 81.3%, the HBeAg-seroconversion at 3 years was 33.3%, HBsAg loss was 0%, the relapse was 27.5%, and the breakthrough was 3.6%. The baseline mean serum HBV-DNA levels was 6.02±1.6 log IU/mL, the mean reduction in serum HBV-DNA level was 5.0±1.5 log IU/mL, baseline ALT level was 274.2±367.9 IU/mL, ALT normalization from 3, 6, 12 months were 47%, 19.4%, 15.8%, respectively. The proportion of residual HBV-DNA levels at 24 weeks was ＜200 IU/mL (78.4%); 0 IU/mL (56.1%), ＜2000 IU/mL (30.9%), respectively. Of all the patients treated with nucleos(t)ide analogues did not differ between baseline and on-treatment factors. The greater proportion of patients with tenofovir treatment was in one group with ALT ＞5xUNL (10.1%), and entecavir treatment in another one with ALT＜5xUNL (48.2%). These elevated baseline HBV-DNA levels were associated with young age, increased serum ALT levels, HBeAg-seropositivity, none liver cirrhosis at study entry. Patients with cirrhosis was associated older age, decreased serum ALT levels, decreased baseline HBV-DNA level, lower reduction of HBV-DNA levels and high risk of hepatocellular carcinoma occurrence. Patient with HBeAg-seronegativity were associated with older age, decreased baseline HBV-DNA levels, lower reduction of HBV-DNA levels, and treatment-naive. Patients with treatment naive were associated with older age, decreased serum ALT levels, decreased baseline HBV-DNA levels, and HBeAg-seronegativity. Normalization of ALT levels was associated with lower HBV-DNA levels after 24 weeks treatment, higher viral suppression after one year treatment, and high reduction of HBV-DNA levels. HBV-DNA undetectable after one year treatment was associated with lower HBV-DNA levels at week 24 with 0 IU/mL, ＜2000 IU/mL, and ＜200 IU/mL respectively, HBeAg-seronegativity, normalization of ALT levels at year 1, month 3, month 6 respectively, and old age ＞65 years old. Independent predictors of ALT values normalization at 1 year was HBV-DNA levels undetectable (hazard ratio, 0.313; 95% confidence interval, 0.105-0.935; p=0.002), and reduction of HBV-DNA levels (hazard ratio, 0.645; 95% confidence level, 0.453-0.920). An independent predictor of HBV-DNA level undetectable at 1 year was early response to HBV-DNA level= 0 IU/mL at 24 weeks (hazard ratio, 0.007; 95% confident interval, 0.001-0.089; p=0.000). Independent predictor of HBV-DNA level ＜200 IU/mL was HBeAg-negative (hazard ratio, 0.265; 95% confidence interval, 0.111-0.634; p=0.003). Independent predictor of HBeAg seroconversion at 3 years was HBV-DNA levels undetectable at 1 year according to this higher Wald values. Conclusion: Continuous oral nucleos(t)ide analogues results in improving biochemical and virological outcomes. Undetectable HBV-DNA at 24 weeks was predictive of viral suppression at 1 year, ALT normalization at 1 year, and HBeAg seroconversion at 3 years. Week 24 HBV-DNA level of ＜200 IU/mL was predictive of favorable long-term outcome in patients with HBeAg-negative.