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Apoptosis of Biliary Epithelial Cells
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
Natalie J. Török, Gregory J. Gores
Bile duct epithelial cells (also referred to as cholangiocytes) are targets of several immune-mediated diseases including primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and graft versus host disease (GVHD) and liver allograft rejection. Ductopenia (decrease in the number of bile ducts per portal tract) and the vanishing bile duct syndrome are considered the end result of these cholangiopathies. The exact mechanisms by which cholangiocytes die in these disease states are not well defined, but apoptosis is a major process. The role of apoptosis is well established in bile duct morphogenesis (ductal plate structure regression), also apoptosis is responsible for tissue regression after induced hyperplasia (the disappearance of proliferated ducts after relief of the biliary obstruction). The mechanism of apoptosis however, in cholangiopathies, such as PBC and PSC is unclear, mainly, because of methodological reasons: apoptosis is a transient phenomenon, and apoptotic bodies are probably quickly eliminated into the lumen. Despite these limitations, apoptosis is readily observed in cholangiocytes during these disease processes. Recently, with use of in vitro techniques major advances have been made in understanding the apoptotic pathways, occurring in the biliary epithelium.
Hepatotoxins
Published in John F. Pohl, Christopher Jolley, Daniel Gelfond, Pediatric Gastroenterology, 2014
Amoxicillin/clavulanate toxicity is the most common antibiotic cause of DILI worldwide. It presents with a cholestatic picture when taken chronically, suggesting cholangiocyte or cholangiocyte–hepatocyte damage. Liver biopsy also reveals eosinophils, suggesting an immunoallergic process, and in more advanced cases ductopenia also known as ‘vanishing bile duct syndrome’. Clavulanate appears to be essential for DILI to occur, because amoxicillin alone will not trigger DILI even in patients shown to be sensitive to amoxicillin/clavulanate. However, it is not known whether clavulanate alone causes DILI. Acute liver failure has been reported but is rare. Treatment consists of stopping the medication.
Fulminant acute liver failure as an unusual presentation of Kawasaki disease
Published in Scandinavian Journal of Rheumatology, 2021
G Anjani, R Deglurkar, RK Pilania, H Chaudhary, K Vaiphei, P Vignesh, S Singh
He received intravenous immunoglobulin (IVIG) infusion 2 g/kg. He was afebrile for 2 days following IVIG infusion. He was continued on supportive care with vitamin K, rifaximin, N-acetyl cysteine, sodium benzoate, lactulose, and intravenous antimicrobials. Two days later, he had a recurrence of high-grade fever spikes, requiring the second dose of IVIG (2 g/kg). Serial echocardiography revealed an increase in the diameters of the coronary arteries suggesting left main coronary artery dilatation (Table 1). Because of persistent high-grade fever spikes and elevated ferritin, a possibility of macrophage activation syndrome was considered and intravenous methylprednisolone at 30 mg/kg/day was administered. After two doses of methylprednisolone, fever spikes became passive, and liver function tests and serum ferritin showed a decreasing trend. However, on day 10, he developed sudden respiratory worsening in the form of increased work of breathing, desaturations, and bilateral diffuse crepitations requiring intubation. He succumbed to death due to pulmonary bleeding. A post-mortem liver biopsy revealed features of ductopenia, cholestasis, and vasculitis (Figure 1D, E).
Phenotype-Genotype Correlation of North Indian Progressive Familial Intrahepatic Cholestasis type2 Children Shows p.Val444Ala and p.Asn591Ser Variants and Retained BSEP Expression
Published in Fetal and Pediatric Pathology, 2020
Suvradeep Mitra, Ashim Das, Baburam Thapa, Rakesh Kumar Vasishta
CK7 (Dako, Denmark; Dilution 1:50) and BSEP (Sigma-Aldrich, Gmbh, Germany; Dilution 1:500) immunohistochemistry was performed on all these cases. pCEA immunostain (Dako, Denmark; Dilution 1:200) was performed as canalicular control. Membranocytoplasmic positivity of the biliary epithelial cells was considered to be the normal expression of CK7. Ductopenia, ductule increase, and ductular metaplasia of the hepatocytes were assessed by CK7 immunostain. Ductopenia was defined as the interlobular bile duct/portal tract ratio of <0.5. Increase in ductules was semiquantitatively scored [Table 1]. These grades were subjective and based on visual analog scale. The ductular metaplasia, defined as aberrant membranocytoplasmic CK7 expression by the hepatocytes albeit usually at a lesser intensity than the ducts/ductules was also scored semiquantitatively [Table 1]. The normal expression of BSEP and pCEA was canalicular. pCEA positivity in the canaliculi with BSEP negativity was considered to be true negative BSEP pattern. The BSEP positivity was compared to pCEA positivity in terms of intensity and percentage area positivity. A low intensity or less percentage area positivity of BSEP was noted.
Old and novel prognostic biomarkers in primary biliary cholangitis
Published in Expert Opinion on Orphan Drugs, 2021
G Mulinacci, A Palermo, Pietro Invernizzi, Marco Carbone
Toronto criteria were developed in a cohort of 69 UDCA-treated PBC patients with paired liver biopsies [29]. They described the lack of biochemical response to UDCA after 2 years of treatment as associated with long-term histological progression in patients with PBC. Indeed, they identified two years after the introduction of UDCA treatment begin as a better performing outcome, since 54% of patients continued to have decreased ALP levels into the second year of UDCA treatment before reaching a plateau. In addition, ductopenia at baseline was a predictive factor for histological progression and treatment failure, suggesting a histological parameter useful to recognize patients at an early stage that could potentially benefit from novel treatments.