Objective To explore the possible mechanism of Huatan Qushi Huoxue Formula（HQHF

化痰祛湿活血方） in treating chronic hepatitis B（CHB） combined with non-alcoholic fatty liver disease（NAFLD）. Methods Sixty SD rats were randomly divided into entecavir group

HQHF group

combination group（entecavir plus HQHF）

and normal group

with 15 rats in each group. Entecavir dispersible tablets at a dose of 0.5 mg/（kg·d） was given by gavage in entecavir group

while HQHF granule at a dose of 15 g/（kg·d） was given by gavage in HQHF group; both entecavir and HQHF granule with same amount mentioned above were administered in combination group; the normal group was fed as normal. Blood was collected after 10 days to prepare medicated serum. In cell experiment

there were seven groups including control group

model group

entecavir serum group

HQHF serum group

combined serum group

agonist group

and combined serum plus agonist group

with three holes in each group. In all groups except for the control group

50μmol/L oleic acid was used for HepG 2.2.15 cells to establish a CHB combined with NAFLD cell model. After modeling

the control group and the model group were given 10% normal rat serum; the entecavir serum group

HQHF serum group

and combined serum group received 10% corresponding entecavir and/or HQHF serum; the agonist group received 10% rat normal serum plus T0901317; combined serum plus agonist group was administered with entecavir and HQHF serum plus T0901317. After 48 hours of culture

the cell viability and apoptosis rate were compared among different groups; liver X receptor a（LXRa）

sterol regulatory element binding protein 1 c（SREBP-1 c）

fatty acid synthase（FAS） mRNA expression

and hepatitis virus（HBV） DNA content in the supernatant cell culture were detected. Results There were no statistically significant differences in cell viability and apoptosis rate between the model group and the control group（P>0.05）. Compared with the model group

the entecavir serum group significantly increased cell viability and decreased apoptosis rate

while the agonist group significantly decreased cell viability and increased apoptotic rate（P<0.01）; and both the HQHF serum group and the combined serum group significantly decreased cell apoptosis rate（P<0.05 or P<0.01）. Compared with the control group

the model group had significantly lower LXRa mRNA and higher HBV DNA content（P<0.01）. Compared with those of the model group

the SREBP-1 c mRNA of the HQHF serum group and the combined serum group significantly decreased

while HBV DNA content of the entecavir serum group and the combined serum group decreased（P<0.01）. The LXRa

SREBP-1 c

FAS mRNA and HBV DNA levels of the agonist group were significantly higher than those of the combined serum group

while the LXRa and SREBP-1 c mRNA levels of the combined serum plus agonist group were lower than those of the agonist group（P<0.01）. Conclusion HQHF may affect the fat synthesis in liver cells by regulating the expression of lipid metabolism-related genes

thereby enhancing the ability of entecavir to inhibit HBV DNA replication.