Correction to: Keratin 7 expression in hepatic cholestatic diseases

AbstractWe evaluated keratin 7 (K7) hepatocellular expression in 92 patients with common types of acute and chronic cholestatic diseases caused by bile duct obstruction/destruction or parenchymal lesions [acute hepatitis (n=20), mixed/pure cholestasis (n=16), primary biliary cholangitis-PBC (n=35), primary sclerosing cholangitis-PSC (n=10), vanishing bile duct syndrome (n=3), complete large bile duct obstruction due to space-occupying lesions (n=8)]. K7 immunohistochemical hepatocellular expression and ductular reaction (DR) were semi-quantitatively assessed. Results were correlated with liver enzyme serum levels, cholestasis type, histological features, hepatocellular Ki67 labelling index (LI) and HepPar1 expression. Hepatocellular K7 expression was detected in 87% (81/92) cases and in all cholestatic disease types with lowest incidence in pure/mixed cholestasis and highest in incomplete bile duct obstruction (iBDO), reaching 100% in PSC. K7-positive hepatocytes had low Ki67 LI (0-5%) retaining HepPar1 expression, irrespective of disease type. PSC cases had high K7 hepatocellular expression even with intact bile ducts, a feature that may aid differential diagnosis of cholestatic syndromes. K7 hepatocellular expression significantly correlated with cholestasis type, bile duct loss and fibrosis stage. It was higher in milder acute cholestatic hepatitis showing inverse correlation with hepatocyte proliferation and serum transaminase levels. In iBDO, younger age independently correlated with high K7 expression, while serum GGT levels showed a nearly significant correlation. Correlation with DR findings implied that K7-positive hepatocytes may result through metaplasia. In conclusion, K7 hepatocellular expression is a sensitive though non-specific marker of cholestasis. It may represent a cytoprotective reaction of resting hepatocytes in cholestasis of longer duration especially in younger patients.

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Supplemental use of Keratin 7 and 19 immunohistochemical staining in liver biopsy diagnosis

10.26226/morressier.578f37fad462b8028d88fe06 ◽

2016 ◽

Author(s):

Rouchelle Dela Cruz

Keyword(s):

Liver Biopsy ◽

Immunohistochemical Staining ◽

Biopsy Diagnosis ◽

Keratin 7

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Mesenteric and Retroperitoneal Mucinous Cystic Neoplasms: A Case Series

International Journal of Surgical Pathology ◽

10.1177/1066896921993536 ◽

2021 ◽

pp. 106689692199353

Author(s):

Benjamin J. Van Treeck ◽

Rachel K. Horton ◽

Hee Eun Lee ◽

Christophe Rosty ◽

Rish K. Pai ◽

...

Keyword(s):

Case Reports ◽

Primordial Germ Cells ◽

Case Series ◽

Cystic Neoplasms ◽

Mucinous Cystic Neoplasms ◽

Abdominal Tumors ◽

Keratin 19 ◽

Liver And Pancreas ◽

Mucinous Epithelium ◽

Keratin 7

Aims. Mucinous cystic neoplasms (MCNs) are cystic neoplasms with mucinous epithelium surrounded by ovarian-like stroma. Extraovarian MCN occurring in the liver and pancreas have been well characterized. However, only rare case reports of MCN arising outside of these locations have been reported. MCNs arising in unusual locations should enter the differential diagnosis of mucinous intra-abdominal tumors and must be distinguished from more common mimics. Therefore, we aimed to examine a series of MCNs of the retroperitoneum and mesentery to characterize the clinicopathologic features of this entity. Methods and results. Seven MCNs arising in the abdominal mesentery or retroperitoneum were retrospectively identified. A clinicopathologic, histologic, and immunohistochemical (keratin 7, keratin 19, keratin 20, calretinin, inhibin-α, steroidogenic factor-1 (SF-1), estrogen receptor (ER), progesterone receptor (PR), PAX8, CDX2, and CD10) analysis was performed. All 7 MCNs were from females with a median age of 41 years old and a median size of 8 cm. All cases demonstrated mucinous with or without concomitant non-mucinous epithelium overlying spindle cell ovarian-like stroma. Luteinized cells were noted. The epithelium was positive for keratin 7 and keratin 19 in all 7 cases, while the stroma expressed ER, PR, and SF-1 in all cases stained. Calretinin was focally positive in the stroma of 3 of 7 cases, while inhibin-α was focally expressed in 5 of 6 cases. Conclusions. These results highlight the clinicopathologic, histologic, and immunophenotypic similarities between MCNs of the mesentery, retroperitoneum, pancreas, and liver. Overlapping features suggest a common histogenesis for all MCNs, which could include periductal fetal mesenchyme, aberrant migration of primordial germ cells, or abnormal differentiation or metaplasia of the embryonic coelomic epithelium.

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Increased Serum Levels of Activated Caspases in Murine and Human Biliary Atresia

Journal of Clinical Medicine ◽

10.3390/jcm10122718 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2718

Author(s):

Omid Madadi-Sanjani ◽

Gunnar Bohlen ◽

Fabian Wehrmann ◽

Julia Andruszkow ◽

Karim Khelif ◽

...

Keyword(s):

Liver Injury ◽

Biliary Atresia ◽

Caspase 3 ◽

Serum Levels ◽

Healthy Individuals ◽

Serological Detection ◽

Caspase Activation ◽

Hepatocyte Apoptosis ◽

Non Invasive ◽

Cholestatic Diseases

In biliary atresia (BA), apoptosis is part of the pathomechanism, which results in progressive liver fibrosis. There is increasing evidence suggesting that apoptotic liver injury can be non-invasively detected by measuring the caspase activity in the serum. The purpose of this study was to investigate whether serological detection of caspase activation mirrors apoptotic liver injury in the infective murine BA-model and represents a suitable biomarker for BA in humans. Analysis showed increased caspase-3 activity and apoptosis in the livers of cholestatic BALB/c mice, which correlated significantly with caspase activation in the serum. We then investigated caspase activation and apoptosis in liver tissues and sera from 26 BA patients, 23 age-matched healthy and 11 cholestatic newborns, due to other hepatopathies. Compared to healthy individuals, increased caspase activation in the liver samples of BA patients was present. Moreover, caspase-3 activity was significantly higher in sera from BA infants compared to patients with other cholestatic diseases (sensitivity 85%, specificity 91%). In conclusion, caspase activation and hepatocyte apoptosis play an important role in experimental and human BA. We demonstrated that serological detection of caspase activation represents a reliable non-invasive biomarker for monitoring disease activity in neonatal cholestatic liver diseases including BA.

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Arbutin Alleviates the Liver Injury of α-Naphthylisothiocyanate-induced Cholestasis Through Farnesoid X Receptor Activation

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.758632 ◽

2021 ◽

Vol 9 ◽

Author(s):

Peijie Wu ◽

Ling Qiao ◽

Han Yu ◽

Hui Ming ◽

Chao Liu ◽

...

Keyword(s):

Bile Acid ◽

Liver Injury ◽

Protective Effect ◽

Bile Acids ◽

Liver Toxicity ◽

Enterohepatic Circulation ◽

Receptor Activation ◽

Farnesoid X Receptor ◽

Bile Acid Metabolism ◽

Cholestatic Diseases

Cholestasis is a kind of stressful syndrome along with liver toxicity, which has been demonstrated to be related to fibrosis, cirrhosis, even cholangiocellular or hepatocellular carcinomas. Cholestasis usually caused by the dysregulated metabolism of bile acids that possess high cellular toxicity and synthesized by cholesterol in the liver to undergo enterohepatic circulation. In cholestasis, the accumulation of bile acids in the liver causes biliary and hepatocyte injury, oxidative stress, and inflammation. The farnesoid X receptor (FXR) is regarded as a bile acid–activated receptor that regulates a network of genes involved in bile acid metabolism, providing a new therapeutic target to treat cholestatic diseases. Arbutin is a glycosylated hydroquinone isolated from medicinal plants in the genus Arctostaphylos, which has a variety of potentially pharmacological properties, such as anti-inflammatory, antihyperlipidemic, antiviral, antihyperglycemic, and antioxidant activity. However, the mechanistic contributions of arbutin to alleviate liver injury of cholestasis, especially its role on bile acid homeostasis via nuclear receptors, have not been fully elucidated. In this study, we demonstrate that arbutin has a protective effect on α-naphthylisothiocyanate–induced cholestasis via upregulation of the levels of FXR and downstream enzymes associated with bile acid homeostasis such as Bsep, Ntcp, and Sult2a1, as well as Ugt1a1. Furthermore, the regulation of these functional proteins related to bile acid homeostasis by arbutin could be alleviated by FXR silencing in L-02 cells. In conclusion, a protective effect could be supported by arbutin to alleviate ANIT-induced cholestatic liver toxicity, which was partly through the FXR pathway, suggesting arbutin may be a potential chemical molecule for the cholestatic disease.

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