However, the FBG level in hepatic steatosis group was significantly higher, supporting the coexistence of dys-regulated glucose metabolism. Previous works found that BMI and TG were independent factors for hepatic steatosis [8], [17] while our findings showed that waist circumference was also DAPT secretase msds associated with hepatic steatosis (Table 3). This result complemented previous findings that BMI and waist circumference were associated with NASH [18]. In addition, we also found uric acid as an independent risk factor for hepatic steatosis, confirming our latest findings that uric acid level was significantly associated with NAFLD [19]. Currently, Entecavir has been confidently considered as first-line monotherapy of CHB, for its potent HBV inhibition ability and a high barrier to resistance [20].

Nevertheless, the effect of anti viral drugs in CHB patients with hepatic steatosis was rarely reported. There was only one article showing none impact of hepatic steatosis on the outcome of peg-��-interferon treatment in CHB patients [21]. Therefore, this study firstly reported the negative effect of hepatic steatosis on Entecavir treatment failure in CHB patients. Such effect is biologically possible, as cellular fat accumulation may decrease the contact area between drugs and hepatocytes, causing reduced bioavailability of Entecavir [22]. Besides, diminished activity of hepatic cytochromes in steatotic hepatocytes may also hamper drug metabolism [23]. In patients with hepatitis C, insulin resistance and obesity coexisted with hepatic steatosis may lead to dysfunction of cellular immune function [24], which might be also true in CHB patients with hepatic steatosis.

To further analyze the association between hepatic steatosis and advanced virological response, we retrospectively separated CHB patients into groups with and without hepatic steatosis and further investigated the overall difference of antiviral effect from 24wk to 96wk. This in-depth analysis showed a significant effect of hepatic steatosis on HBV-DNA clearance and ALT normalization (Table 5). Our finding was of clinical importance as it may change current mode of antiviral therapy in CHB patients with hepatic steatosis. Moreover, it is rational to further investigate the effect of treating hepatic steatosis on HBV antiviral therapy.

We have carried out an RCT (ClinicalTrials: NCT01148576) by Dacomitinib using Entecavir with essentiale or vitamin E to treat CHB patients with hepatic steatosis. Besides, we did a preliminary multivariant analysis on CHB patients without steatosis and found ALT was significantly associated with Entecavir treatment failure at 24wk (p=0.03), in contrast with our previous finding (Table 3). This result supports our hypothesis that hepatic steatosis caused ALT elevation may mask real HBV activation caused ALT elevation. Nevertheless, such association did not show statistic significance at 48wk and 96wk, which needs further study with larger subjects.