Abstract: Objective To investigate the dynamic changes of Toll-like receptor 4 (TLR4) and intestinal flora in the progression of primary liver cancer, and to analyze their relationship with prognosis.Methods 100 patients with chronic hepatitis B (HBV), 80 patients with cirrhosis and HBV, and 60 patients with hepatocellular carcinoma and HBV were enrolled as subjects. They were named HBV group, cirrhosis group and liver cancer group, and matched with age and gender. One hundred healthy subjects were used as a control group. The expression of TLR4 on the surface of peripheral blood mononuclear cells was detected by flow cytometry. Fresh feces were collected from each group, and the distribution of intestinal flora was detected. The relationship between the two groups was analyzed. The expression of TLR4 and the distribution of intestinal flora in peripheral blood mononuclear cells of each group were compared, and the relationship between the expression of TLR4 and the prognosis of liver cancer patients was analyzed. Results The positive rates of CD14⁺TLR4⁺ monocytes in the peripheral blood of the control group, HBV group, liver cirrhosis group and liver cancer group were gradually increased, which were (34.92±4.79)%, (41.92±7.46)%, (49.21±8.83)%, and (57.62±10.58)% respectively, the difference between the four groups was statistically significant (F=78.624, P=0.000). The content of bifidobacteria in the control group, HBV group, liver cirrhosis group and liver cancer group decreased sequentially as (10.73±2.91) log CFU/g, (8.15±2.04) log CFU/g, (6.33±1.32) log CFU/g, and (5.21±0.87) log CFU/g, the difference between the four groups was statistically significant (F=15.932, P=0.000); the content of enterococci in the control group, HBV group, cirrhosis group and liver cancer group increased in turn, respectively (4.91±0.78) log CFU/g, (6.44±1.29) log CFU/g, (8.11±2.08) log CFU/g and (10.21±2.77) log CFU/g, the difference between the four groups was statistically significant (F= 12.372, P=0.000). According to Pearson correlation analysis, the expression of TLR4 on the surface of monocytes was negatively correlated with Lactobacillus and Bifidobacteria (P<0.05), and the correlation coefficients were -0.643 and -0.672 respectively. It was positively correlated with Enterococcus and Escherichia coli. (P<0.05), the correlation coefficients were 0.771 and 0.734 respectively. During the follow-up of 1 year, 18 of the 60 patients with liver cancer recurred and 15 died. The positive rates of CD14⁺TLR4⁺ monocytes in peripheral blood in relapsed and non-relapsed patients were (59.32±9.17)% and (55.21±5.23)%, respectively, and the difference was statistically significant (t=2.200, P=0.032). The positive rates of CD14⁺TLR4⁺ monocytes in peripheral blood of the deceased and survivors were (61.04±10.23)% and (53.29±8.11)%, respectively, and the difference was statistically significant (t=2.998, P=0.004). Compared with non-recurring and survivors, the content of bifidobacteria and lactobacilli in relapsed and deceased patients was significantly reduced, but the contents of Enterococcus and Escherichia coli were significantly increased, the difference was statistically significant (P<0.05).Conclusion TLR4 can promote the progression of HBV to liver cancer, which is significantly correlated with the changes of intestinal flora. Both of them have certain value in the prognosis monitoring of liver cancer.

Key words: primary liver cancer, Toll-like receptor 4, intestinal flora, prognosis