[Analysis of clinical characteristics and risk factors of hepatic fibrosis in children with chronic hepatitis B combined with metabolic-related fatty liver disease].

Objective: To compare the clinical and pathological features of children with chronic viral hepatitis B combined with metabolic-associated fatty liver disease (CHB-MAFLD) and chronic viral hepatitis B alone (CHB alone), and to further explore the effect of MAFLD on the progression of hepatic fibrosis in CHB. Methods: 701 initially treated CHB children confirmed by liver biopsy admitted to the Fifth Medical Center of the PLA General Hospital from January 2010 to December 2021 were collected continuously. They were divided into CHB-MAFLD and CHB-alone groups according to whether they were combined with MAFLD. A retrospective case-control study was conducted. CHB-MAFLD was used as the case group, and 1:2 propensity score matching was performed with the CHB alone group according to age and gender, including 56 cases in the CHB-MAFLD group and 112 cases in the CHB alone group. The body mass index (BMI), metabolic complications, laboratory indicators, and pathological characteristics of liver tissue were compared between the two groups. The related factors affecting liver disease progression in CHB were analyzed by a binary logistic regression model. The measurement data between groups were compared using the t-test and rank sum test. The χ (2) test was used for the comparison of categorical data between groups. Results: Alanine aminotransferase (ALT, P = 0.032) and aspartate aminotransferase (AST, P = 0.003) levels were lower in the CHB-MAFLD group than those in the CHB alone group, while BMI (P < 0.001), triglyceride (TG, P < 0.001), total cholesterol (P = 0.016) and the incidence of metabolic syndrome (P < 0.001) were higher in the CHB alone group. There were no statistically significant differences in HBsAg quantification or HBV DNA load between the two groups (P > 0.05). Histologically, the proportion of significant liver fibrosis (S2-S4) was higher in the CHB-MAFLD group than that in the CHB alone group (67.9% vs. 49.1%, χ (2) = 5.311, P = 0.021). Multivariate regression results showed that BMI (OR = 1.258, 95% CI: 1.145 ~ 1.381, P = 0.001) and TG (OR = 12.334, 95% CI: 3.973 ~ 38.286, P < 0.001) were the risk factors for hepatic steatosis occurrence in children with CHB. MAFLD (OR = 4.104, 95% CI: 1.703 ~ 9.889, P = 0.002), liver inflammation (OR = 3.557, 95% CI: 1.553 ~ 8.144, P = 0.003), and γ-glutamyl transferase (OR = 1.019, 95% CI: 1.001 to 1.038, P = 0.038) were independent risk factors for significant hepatic fibrosis in children with CH. Conclusion: MAFLD occurrence is related to metabolic factors in children with CHB. Additionally, the combination of MAFLD may promote liver fibrosis progression in CHB patients.

Hydrogenated castor oil nanoparticles as carriers for the subcutaneous administration of tilmicosin: in vitro and in vivo studies.

Tilmicosin-loaded solid lipid nanoparticles (SLN) were prepared with hydrogenated castor oil (HCO) by o/w emulsion-solvent evaporation technique. The nanoparticle diameters, surface charges, drug loadings and encapsulation efficiencies of different formulations were 90 approximately 230 nm, -6.5 approximately -12.5 mV, 40.3 approximately 59.2% and 5.7 approximately 11.7% (w/w), respectively. In vitro release studies of the tilmicosin-loaded nanoparticles showed a sustained release and the released tilmicosin had the same antibacterial activity as that of the free drug. Pharmacokinetics study after subcutaneous administration to Balb/c mice demonstrated that a single dose of tilmicosin-loaded nanoparticles resulted in sustained serum drug levels (>0.1 microg/mL) for 8 days, as compared with only 5 h for the same amount of tilmicosin phosphate solution. The time to maximum concentration (Tmax), half-life of absorption (T(1/2) ab) and half-life of elimination (T(1/2) el) of tilmicosin-loaded nanoparticles were much longer than those of tilmicosin phosphate solution. Tissue section showed that drug-loaded nanoparticles caused no inflammation at the injection site. Cytotoxicity study in cell culture and acute toxicity test in mice demonstrated that the nanoparticles had little or no toxicity. The results of this exploratory study suggest that the HCO-SLN could be a useful system for the delivery of tilmicosin by subcutaneous administration.