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Objective@#To investigate the inhibitory effect of AKR1B10 inhibitor combined with sorafenib on hepatocellular carcinoma (HCC) xenograft growth.@*Methods@#HepG2 xenograft model was established in nude mice. The mice were then randomly divided into four groups: control group, epalrestat monotherapy group, sorafenib monotherapy group and combination treatment group. Tumor volume, tumor weight, T/C ratio and the change in body weight of nude mice in each group were compared to evaluate the curative effect. Immunohistochemistry staining was used to detect the expression of Ki-67 in tumor tissues to evaluate the proliferation status of tumor cells. One-way analysis of variance was used to compare the differences between the groups. Student’s t-test was used to test means of two groups and chi-square test was used for multiple samples.@*Results@#The differences of the grafted tumor volume before and after treatment between the control group, epalrestat group, sorafenib group and combined therapy group was 238.940 ± 39.813, 124.991 ± 84.670, -26.111 ± 11.518, and -54.072 ± 17.673(mm3), respectively, (F = 37.048, P < 0.001). The tumor mass were 0.273 ± 0.140, 0.158 ± 0.078, 0.079 ± 0.054, 0.045 ± 0.024 (g), (F = 16.594, P < 0.001); T/C ratio were 100%, 57.9%, 28.9%, 16.5%, and Ki-67 positive rate were 23.295 ± 6.218, 13.503 ± 3.392, 7.325 ± 2.257, 4.664 ± 1.189 (%), (χ2 = 822.203, P < 0.001) . The tumor volume (t = -3.579, P = 0.002) and Ki-67 positive rate (t = -10.003, P < 0.001) in epalrestat monotherapy group were significantly lower than control group. The tumor volume (t = 2.056, P = 0.025), tumor mass (t = 2.101, P = 0.043), and Ki-67 positive rate (t = -2.850, P = 0.005) in combination treatment group were significantly lower than sorafenib monotherapy group. Compared with the control group, the body weight of nude mice in the treatment group decreased to a certain extent, but there was no statistically significant difference between epalrestat monotherapy group and control group (t = -1.599, P = 0.262), and combined therapy and sorafenib monotherapy group (t = -0.051, P = 0.96).@*Conclusion@#AKR1B10 inhibitor enhanced the inhibitory effect of sorafenib on hepatocellular carcinoma xenograft.
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Objective@#To explore the difference of liver inflammation and fibrosis in patients with chronic hepatitis B virus (HBV) infection and chronic hepatitis C virus (HCV) infection, and to investigate the relationship between hepatic pathology and alanine aminotransferase (ALT).@*Methods@#57 patients with chronic HCV infection and 346 patients with chronic HBV infection who were hospitalized at Shengjing Hospital of China Medical University from January 2012 to September 2016 were enrolled. In chronic HBV infection, including 88 cases whose ALT were more than two times of upper limited of normal (ALT≥2×ULN) and 258 cases whose ALT were less than two times of upper limited of normal (ALT < 2×ULN).All the patients were underwent liver biopsy. Chronic HBV infection (ALT≥2×ULN and ALT < 2×ULN) and chronic HCV infection were compared respectively. Statistical analyses were performed using a Univariate χ²-test and Mann–Whitney U test for comparison. Correlations between variables were analyzed using Spearman's rank correlation.@*Results@#In chronic HBV infection group, 169 cases (48.8%) had inflammation grade≥2 (G≥2), 98 cases (28.3%) had fibrosis stage≥2 (S≥2), 81 cases (23.4%) with G≥2 and S≥2.In the ALT < 2×ULN group, there were 109 cases (42.2%) with G≥2, 62 cases (24%) with S≥2, 49 cases (19%) with G≥2 and S≥2. In the ALT≥2×ULN group, 60 cases (68.2%) with G≥2, 35 cases (39.8%) with S≥2, 31 cases (35.2%) with G≥2 and S≥2. The grade of inflammation and fibrosis have significantly different between ALT≥2×ULN group and ALT < 2×ULN group (χ² = 17.66, χ² = 8.06, P < 0.01). In chronic HCV infection group, 47 cases (82.5%) with G≥2, 20 cases (35.1%) with S≥2, 20 cases (35.1%) with G≥2 and S≥2. ALT had no correlation with inflammation and fibrosis (P > 0.05). The grade of inflammation was significantly different between chronic HCV infection and chronic HBV infection whose ALT < 2×ULN (χ² = 30.19, P < 0.01) but the fibrosis have no difference (χ² = 2.96, P > 0.05). Compared with chronic HBV infection whose ALT≥2×ULN, both inflammation and fibrosis had no significantly different (χ² = 3.65, χ² = 0.32, P > 0.05 respectively).@*Conclusion@#In chronic HBV infection whose ALT < 2×ULN, about 30%-40% liver tissue with significant necroinflammation and /or fibrosis. About 80% chronic HCV infection with significant necroinflammation, and the grade of inflammation has no correlation with ALT. The grade of inflammation has significantly different between chronic HCV infection group and chronic HBV infection group whose ALT < 2×ULN.
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Objective To develop a simple model for the noninvasive diagnosis of liver fibrosis in patients with chronic hepatitis B and to testify its diagnostic value. Methods One hundred and ninety patients with chronic hepatitis B who had undergone liver biopsy were divided into 2 groups:one for developing the model(n=110) and one for validation(n=80). Histological staging of liver fibrosis,assessed blindly and independently by 2 pathologists,was determined according to Scheuer fibrosis score.Twenty markers involved in the study were analyzed initially in the estimation group to derive a predictive model to discriminate the stages of fibrosis.The model created was then assessed with receiver operating characteristic curve(ROC)analysis. It was also applied to the validation group to test its accuracy. Results Haptoglobin(HPT),γ-glutamyl transpeptidase(GGT)and platelet were identified by logistic regression analysis as independent factors of fibrosis. A model developed from the above three markers was established to predict the stage of fibrosis(S). In ROC analysis,the area under curve(AUC) for identifying S≥1,S≥2,S≥3 and S=4 was 0.832,0.835,0.820 and 0.843 respectively. The model had a similar AUC in the vatidation group without statistically significant difierence. Using a cut-off of ＜0.18, significant fibrosis (S≥2)could be excluded in 27 patients of the total patient population(negative predictive value 90%).Similarly,applying a cut-off ≥0.70,significant fibrosis could be identified correctly in 67 patients of the total patient population(positive predictive value 82.7%).The model had a high level of diagnostic value in patients with HBeAg-positive chronic hepatitis B as well as in patients with HBeAg-negative chronic hepatitis B(AUC for identifying S≥2,0.857 vs 0.802). Restricting biopsy to patients with intermediate scores(≥0.70 and ＜0.18) may prevent liver biopsies in 58.4% of the patients while maintaining 84.7% accuracy. Conclusions A model including HPT,GGT and platelet is a simple and reliable index for predicting significant fibrosis in patients with HBeAg-positive chronic hepatitis B as well as in patients with HBeAg-negative chronic hepatitis B.