Hepatocellular Ballooning is Due to Highly Pronounced Glycogenosis Potentially Associated with Steatosis and Metabolic Reprogramming  

作　　者：Silvia Ribback Kristin Peters Mohd Yasser Jessica Prey Paula Wilhelmi Qin Su Frank Dombrowski Peter Bannasch 

机构地区：[1]Institut für Pathologie,Universitaetsmedizin Greifswald,Greifswald,Germany [2]Cell Marque,Millipore-Sigma,Rocklin,CA,USA [3]German Cancer Research Center(DKFZ),Heidelberg,Germany

出　　处：《Journal of Clinical and Translational Hepatology》2024年第1期52-61,共10页临床与转化肝病杂志（英文版）

基　　金：funded by the Deutsche Forschungsgemeinschaft(DFG),grant numbers RI 2695/1-1 and RI 2695/1-3。

摘　　要：Background and Aims:Hepatocellular ballooning is a common finding in chronic liver disease,mainly characterized by rarefied cytoplasm that often contains Mallory-Denk bodies(MDB).Ballooning has mostly been attributed to degeneration but its striking resemblance to glycogenotic/steatotic changes characterizing preneoplastic hepatocellular lesions in animal models and chronic human liver diseases prompts the question whether ballooned hepatocytes(BH)are damaged cells on the path to death or rather viable cells,possibly involved in neoplastic development.Methods:Using specimens from 96 cirrhotic human livers,BH characteristics were assessed for their glycogen/lipid stores,enzyme activities,and proto-oncogenic signaling cascades by enzyme-and immunohistochemical approaches with serial paraffin and cryostat sections.Results:BH were present in 43.8%of cirrhotic livers.Particularly pronounced excess glycogen storage of(glycogenosis)and/or lipids(steatosis)were characteristic,ground glass features and MDB were often observed.Decreased glucose-6-phosphatase,increased glucose-6-phosphate dehydrogenase activity and altered immunoreactivity of enzymes involved in glycolysis,lipid metabolism,and cholesterol biosynthesis were discovered.Furthermore,components of the insulin signaling cascade were upregulated along with insulin dependent glucose transporter glucose transporter 4 and the v-akt murine thymoma viral oncogene homolog/mammalian target of rapamycin signaling pathway associated with de novo lipogenesis.Conclusions:BH are hallmarked by particularly pronounced glycogenosis with facultative steatosis,many of their features being reminiscent of metabolic aberrations documented in preneoplastic hepatocellular lesions in experimental animals and chronic human liver diseases.Hence,BH are not damaged entities facing death but rather viable cells featuring metabolic reprogramming,indicative of a preneoplastic nature.

关 键 词：Chronic liver disease Carbohydrate metabolism Insulin signaling PRENEOPLASIA Metabolic reprogramming 

分 类 号：R575[医药卫生—消化系统]