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

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Journal of Clinical and Translational Hepatology 2024年第1期12卷 52-61页

作者： Silvia Ribback Kristin Peters Mohd Yasser Jessica Prey Paula Wilhelmi Qin Su Frank Dombrowski Peter Bannasch Institut für Pathologie Universitaetsmedizin GreifswaldGreifswaldGermany cell marque Millipore-SigmaRocklinCAUSA German Cancer Research Center(DKFZ) HeidelbergGermany

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 ***: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 ***:BH were present in 43.8%of cirrhotic *** pronounced excess glycogen storage of(glycogenosis)and/or lipids(steatosis)were characteristic,ground glass features and MDB were often *** glucose-6-phosphatase,increased glucose-6-phosphate dehydrogenase activity and altered immunoreactivity of enzymes involved in glycolysis,lipid metabolism,and cholesterol biosynthesis were ***,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 ***: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 ***,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

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Clear cell hepatocellular carcinoma: origin,metabolic traits and fate of glycogenotic clear and ground glass cells

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Hepatobiliary & Pancreatic Diseases International 2017年第6期16卷 570-594页

作者： Peter Bannasch Silvia Ribback Qin Su Doris Mayer German Cancer Research Center HeidelbergGermany Institut fur Pathologie Universitatsmedizin Greifswald Greifswald Germany cell marque Millipore-Sigma Rocklin USA

Clear cell hepatocellular carcinoma(CCHCC)has hitherto been considered an uncommon, highly differentiated variant of hepatocellular carcinoma(HCC) with a relatively favorable prognosis. CCHCC is composed of mixtures of clear and/or acidophilic ground glass hepatocytes with excessive glycogen and/or fat and shares histology, clinical features and etiology with common HCCs. Studies in animal models of chemical, hormonal and viral hepatocarcinogenesis and observations in patients with chronic liver diseases prone to develop HCC have shown that the majority of HCCs are preceded by, or associated with, focal or diffuse excessive storage of glycogen(glycogenosis) which later may be replaced by fat(lipidosis/steatosis). In ground glass cells, the glycogenosis is accompanied by proliferation of the smooth endoplasmic reticulum, which is closely related to glycogen particles and frequently harbors the hepatitis B surface antigen(HBs Ag).From the findings in animal models a sequence of changes has been established, commencing with preneoplastic glycogenotic liver lesions, often containing ground glass cells, and progressing to glycogen-poor neoplasms via various intermediate stages, including glycogenotic/lipidotic clear cell foci, clear cell hepatocellular adenomas(CCHCA) rich in glycogen and/or fat, and CCHCC. A similar process seems to take place in humans, with clear cells frequently persisting in CCHCC and steatohepatitic HCC, which presumably represent intermediate stages in the development rather than particular variants of HCC. During the progression of the preneoplastic lesions,the clear and ground glass cells transform into cells characteristic of common HCC. The sequential cellular changes are associated with metabolic aberrations, which start with an activation of the insulin signaling cascade resulting in preneoplastic hepatic glycogenosis. The molecular and metabolic changes underlying the glycogenosis/lipidosis are apparently responsible for the dramatic metabo

关键词： clear cell hepatocellular carcinoma phenotypic heterogeneity glycogenosis lipidosis preneoplastic glycogenosis progression metabolic aberrations

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Hepatocellular carcinoma and type 2 diabetes mellitus: cytokeratin 8/18 expression in hepatocellular carcinoma and glycogen-storing hepatocytes

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Hepatoma Research 2016年第1期2卷 229-230页

作者： Kunio Takegoshi Eikichi Okada Qin Su Takegoshi Internal Medicine Clinic TakaokaToyama 933-0014Japan Pathological Division of Takaoka City Hospital TakaokaToyama 933-8550Japan cell marque Sigma-AldrichRocklinCA 95677USA

Sir,We have reported two patients with hepatocellular carcinoma(HCC)and type 2 diabetes mellitus(T2DM),who showed abundant glycogen in their liver parenchyma but a marked reduction of glycogen content in HCC.[1]It was suggested that the latter was associated with appearance of a Warburg type glycolysis[1]and discussed in some detail.[2]

关键词： hepatocellular mellitus diabetes

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