Institute of Pathology, University Medical Center Mainz, 55131 Mainz, Germany.
Institute of Pathology, University Hospital Wuerzburg, 97080 Wuerzburg, Germany.
Int J Mol Sci. 2022 Dec 7;23(24):15456. doi: 10.3390/ijms232415456.
Chronic infection with hepatitis C (HCV) is a major risk factor in the development of cirrhosis and hepatocellular carcinoma. Lipid metabolism plays a major role in the replication and deposition of HCV at lipid droplets (LDs). We have demonstrated the importance of LD-associated proteins of the perilipin family in steatotic liver diseases. Using a large collection of 231 human liver biopsies with HCV, perilipins 1 and 2 have been localized to LDs of hepatocytes that correlate with the degree of steatosis and specific HCV genotypes, but not significantly with the HCV viral load. Perilipin 1- and 2-positive microvesicular steatotic foci were observed in 36% of HCV liver biopsies, and also in chronic hepatitis B, autoimmune hepatitis and mildly steatotic or normal livers, but less or none were observed in normal livers of younger patients. Microvesicular steatotic foci did not frequently overlap with glycogenotic/clear cell foci as determined by PAS stain in serial sections. Steatotic foci were detected in all liver zones with slight architectural disarrays, as demonstrated by immunohistochemical glutamine synthetase staining of zone three, but without elevated Ki67-proliferation rates. In conclusion, microvesicular steatotic foci are frequently found in chronic viral hepatitis, but the clinical significance of these foci is so far not clear.
慢性丙型肝炎（HCV）感染是肝硬化和肝细胞癌发展的主要危险因素。脂代谢在 HCV 在脂滴（LDs）中的复制和沉积中起主要作用。我们已经证明了脂滴相关蛋白 perilipin 家族在脂肪性肝病中的重要性。使用包含 231 例 HCV 人类肝活检的大型数据集，发现 perilipin 1 和 2 定位于与脂肪变性程度和特定 HCV 基因型相关的肝细胞 LD，但与 HCV 病毒载量无显著相关性。在 36%的 HCV 肝活检中观察到 perilipin 1 和 2 阳性的微泡性脂肪性病灶，也在慢性乙型肝炎、自身免疫性肝炎和轻度脂肪性或正常肝中观察到，但在年轻患者的正常肝中观察到的较少或没有。微泡性脂肪性病灶在连续切片的 PAS 染色中与糖原性/透明细胞病灶不常重叠。通过对第三区的谷氨酰胺合成酶免疫组化染色显示，在所有肝区均检测到脂肪性病灶，且仅有轻微的结构紊乱，但 Ki67 增殖率无升高。总之，微泡性脂肪性病灶在慢性病毒性肝炎中经常发现，但这些病灶的临床意义目前尚不清楚。
