Borges Valéria F A, Cotrim Helma P, Andrade Antônio Ricardo C F, Mendes Liliana S C, Penna Francisco G C, Silva Marcelo C, Salomão Frederico C, Freitas Luiz A R
Postgraduate Program in Medicine and Health, Federal University of Bahia, Salvador 40026-010, Brazil.
School of Medicine of Bahia, Federal University of Bahia, Salvador 40026-010, Brazil.
Diagnostics (Basel). 2024 Aug 19;14(16):1804. doi: 10.3390/diagnostics14161804.
Cholangiopathy has been described in survivors of severe COVID-19, presenting significant clinical parallels to the pre-pandemic condition of secondary sclerosing cholangitis in critically ill patients (SSC-CIP). We aimed to examine the liver histopathology of individuals with persistent cholestasis after severe COVID-19.
We subjected post-COVID-19 cholestasis liver samples to routine staining techniques and cytokeratin 7 immunostaining and semi-quantitatively analyzed the portal and parenchymal changes.
All ten patients, five men, had a median age of 56, an interquartile range (IQR) of 51-60, and required intensive care unit and mechanical ventilation. The median and IQR liver enzyme concentrations proximal to biopsy were in IU/L: ALP 645 (390-1256); GGT 925 (664-2169); ALT 100 (86-113); AST 87 (68-106); and bilirubin 4 (1-9) mg/dL. Imaging revealed intrahepatic bile duct anomalies and biliary casts. We performed biopsies at a median of 203 (150-249) days after molecular confirmation of infection. We found portal and periportal fibrosis, moderate-to-severe ductular proliferation, and bile duct dystrophy in all patients, while we observed hepatocyte biliary metaplasia in all tested cases. We observed mild-to-severe parenchymal cholestasis and bile plugs in nine and six cases. We also observed mild swelling of the arteriolar endothelial cells in five patients. We observed a thrombus in a small portal vein branch and mild periductal fibrosis in one case each. One patient developed multiple small biliary infarctions. We did not observe ductopenia in any patient.
The alterations were like those observed in SSC-CIP; however, pronounced swelling of endothelial cells, necrosis of the vessel walls, and thrombosis in small vessels were notable.
在重症新型冠状病毒肺炎（COVID-19）幸存者中已发现胆管病，其临床表现与大流行前危重症患者继发性硬化性胆管炎（SSC-CIP）的情况有显著相似之处。我们旨在研究重症COVID-19后持续性胆汁淤积患者的肝脏组织病理学。
我们对COVID-19后胆汁淤积的肝脏样本进行常规染色技术和细胞角蛋白7免疫染色，并对门静脉和实质变化进行半定量分析。
所有10例患者（5例男性）的中位年龄为56岁，四分位间距（IQR）为51 - 60岁，均需要重症监护病房治疗及机械通气。活检前肝脏酶浓度的中位数及IQR（单位为IU/L）分别为：碱性磷酸酶（ALP）645（390 - 1256）；γ-谷氨酰转移酶（GGT）925（664 - 2169）；丙氨酸转氨酶（ALT）100（86 - 113）；天冬氨酸转氨酶（AST）87（68 - 106）；胆红素4（1 - 9）mg/dL。影像学检查显示肝内胆管异常和胆泥。我们在感染分子确诊后的中位203（150 - 249）天进行活检。我们发现所有患者均有门静脉和门周纤维化、中度至重度小胆管增生以及胆管营养不良，而在所有检测病例中均观察到肝细胞胆管化生。9例和6例患者分别观察到轻度至重度实质胆汁淤积和胆栓。5例患者还观察到小动脉内皮细胞轻度肿胀。我们在1例患者的一条小门静脉分支中观察到血栓，在另1例患者中观察到轻度导管周围纤维化。1例患者出现多个小胆管梗死。所有患者均未观察到小胆管减少。
这些改变与SSC-CIP中观察到的改变相似；然而，内皮细胞明显肿胀、血管壁坏死和小血管血栓形成较为显著。
