Influence of hepatitis B combined with hepatic fibrosis on endoge-nous and exogenous metabolism and therapeutic implications
10.12092/j.issn.1009-2501.2024.08.002
- VernacularTitle:乙肝合并肝纤维化对内外源性代谢的影响及治疗学启示
- Author:
Jie NI
1
;
Xiaodan HONG
;
Ke JI
;
Yuanwei JIA
;
Guangji WANG
;
Jingwei ZHANG
Author Information
1. 中国药科大学药物代谢动力学重点实验室,南京 210009,江苏
- Keywords:
hepatitis B combined with hepatic fi-brosis;
endogenous metabolism;
metabolic activa-tion of tenofovir ester;
combination with glycyrrhi-zic acid
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2024;29(8):853-860
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To study the effect of hepatitis B combined with hepatic fibrosis on endogenous and exogenous metabolism of liver and the effect of glycyrrhizic acid combined with tenofovir(TFV)es-ter on anti-HBV efficacy.METHODS:Hepatitis B mouse was induced by chronic CCI4 to form a mod-el of hepatitis B with hepatic fibrosis.H&E staining,Sirius Red Staining,α-SMA immunohistochemistry were used to detect pathological changes in liver tissue.The changes of liver endogenous metabo-lism in mice with hepatitis B and hepatic fibrosis were detected by metabolomics.LC-MS/MS was used to investigate the plasma and liver concentra-tions of TFV and its active metabolite(TFV-DP),for investigating the changes of exogenous metabo-lism.RESULTS:HBV+CCl4 mice showed fibrosis symptoms such as liver injury and collagen deposi-tion.Hepatitis B combined with hepatic fibrosis af-fected nucleotide metabolism,amino acid metabo-lism,tricarboxylic acid cycle,pentose phosphate pathway and other endogenous metabolism,low-ered the hepatic level of TFV-DP,and decreased the antiviral efficacy.By combining with glycyrrhizic acid or forming a self-assembled preparation,the hepatic level of TFV-DP was improved,and the anti-viral efficacy was enhanced.CONCLUSIONS:Hepati-tis B combined with hepatic fibrosis affected both endogenous and exogenous metabolism of liver.Different forms of combination of glycyrrhizic acid and TFV could elevate the level of TFV-DP in liver and improve the antiviral efficacy in HBV+CCI4 mice.
