HYPERTENSION AS A MANIFESTATION OF COVID-19 PNEUMONIA

This clinical case represents an unusual manifestation of COVID-19 pneumonia which started as arterial hypertension as well as the development of post-viral inflammatory complications and long-covid syndrome. Several factors such as hypertension, bile duct disease, and age can affect the duration of COVID which can lead to long COVID

Human extrahepatic and intrahepatic cholangiocyte organoids show region-specific differentiation potential and model cystic fibrosis-related bile duct disease

The development, homeostasis, and repair of intrahepatic and extrahepatic bile ducts are thought to involve distinct mechanisms including proliferation and maturation of cholangiocyte and progenitor cells. This study aimed to characterize human extrahepatic cholangiocyte organoids (ECO) using canonical Wnt-stimulated culture medium previously developed for intrahepatic cholangiocyte organoids (ICO). Paired ECO and ICO were derived from common bile duct and liver tissue, respectively. Characterization showed both organoid types were highly similar, though some differences in size and gene expression were observed. Both ECO and ICO have cholangiocyte fate differentiation capacity. However, unlike ICO, ECO lack the potential for differentiation towards a hepatocyte-like fate. Importantly, ECO derived from a cystic fibrosis patient showed no CFTR channel activity but normal chloride channel and MDR1 transporter activity. In conclusion, this study shows that ECO and ICO have distinct lineage fate and that ECO provide a competent model to study extrahepatic bile duct diseases like cystic fibrosis.

Investigation and management of jaundice

Haem molecules are degraded in macrophages to biliverdin and then to bilirubin, which is selectively removed by hepatocytes from sinusoidal blood and conjugated, chiefly with two glucuronic acid moieties. Conjugated bilirubin is excreted into the bile, but in many liver diseases it refluxes back into blood from which some is filtered into and darkens the urine (choluria). In the distal intestine, conjugated bilirubin is deconjugated and reduced to a series of uro- and stercobilinogens that give the normal colour to faeces. Jaundice is the clinical sign of hyperbilirubinaemia and usually indicates disease of the liver or biliary tree. Dark urine and pale stools indicate cholestasis. Stigmata of chronic liver disease do not define the cause of jaundice. Unconjugated hyperbilirubinaemia—presents with raised serum bilirubin levels and normal other liver-related blood tests. Causes include haemolysis and benign inherited unconjugated hyperbilirubinaemia (i.e. Gilbert’s syndrome). Conjugated hyperbilirubinaemia—routine liver-related blood tests cannot alone differentiate between intra- and extrahepatic causes of jaundice although high levels of transferases suggests hepatitis (e.g. viral, autoimmune) or hepatic necrosis (e.g. paracetamol). Alcohol and drug histories are needed in those with both elevated alkaline phosphatase and transferases. Extrahepatic cholestasis should be sought by abdominal ultrasonography to detect a dilated intra- and/or extrahepatic biliary tree (and often also to reveal its cause, e.g. gallstones, tumour). Further investigation depends on the clinical context: (1) likely large bile duct disease—endoscopic retrograde cholangiopancreatography, magnetic resonance cholangiography, and endoscopic ultrasonography; (2) likely intrahepatic cholestasis—autoantibodies, immunoglobulins, and liver biopsy.

Timing of the termination of mechanical jaundice after antegrade and retrograde decompressive surgeries in mechanical jaundice of various genesis

Aim: to determine in a comparative aspect the effectiveness of various minimally invasive decompressive operations in mechanical jaundice of different genesis. Materials and methods. In 135 patients with mechanical jaundice, the rate of bile duct resolution after cholecystostomy and percutaneous cholangiostomy was studied on the background of pancreatic head tumor. In 643 patients with obstructive bile duct disease in cholelithiasis, timing of the termination of jaundice after minimally invasive retrograde (endoscopic papillosphincterotomy (EPT) and EPT with transpapillary drainage) and percutaneous antegrade (cholecystostomy and cholangiostomy) of decompressive operations was studied. Result. Upon cholelithiasis and hyperbilirubinemia less than 100 μmol/l, jaundice is terminated after both variants of retrograde decompression within 3–5 days, antegrade interventions increase these terms by half. Comparison of retrograde and antegrade decompressive surgeries in mechanical jaundice of medium and severe degree on the background of cholelithiasis indicates that the rate of termination of bile stasis is the highest after EPT with transpapillary drainage. Isolated EPT and percutaneous cholangiostoma with medium-grade gallstones increase the duration of jaundice termination by an average of one week. Upon hyperbilirubinemia more than 200 μmol/l, cholangiostomy is not worse than transpapillary drainage. The longest termination period of obstructive jaundice (28–30 days) is observed after superimposition of microcholecystostoma. In patients with jaundice of a mild degree of tumor genesis, no differences in the results were revealed after both variants of percutaneous decompression. Upon hyperbilirubinemia above 100 μmol/l, when cholangio- and cholecystostomy were compared, a higher rate of decrease in serum bilirubin was observed after percutaneous interventions with a cholecystostomy. Conclusion. At all severity levels of mechanical jaundice on the background of cholelithiasis, the best way of decompression is endoscopic papillotomy with transpapillary drainage. In obturation bile stasis upon the pancreatic head tumor, the best decompressive effect is observed after percutaneous cholecystoostomy.

Recombinant adenylate kinase 3 from liver fluke Clonorchis sinensis for histochemical analysis and serodiagnosis of clonorchiasis

Due to the lack of an effective prophylactic intervention and diagnosis, human liver fluke Clonorchis sinensis continues to afflict a large human population, causing a chronic inflammatory bile duct disease. With an aim to identify target antigens for sensitive serodiagnosis, adenylate kinase 3 of C. sinensis (CsAK3) was successfully expressed in soluble form in Escherichia coli by fusion to an RNA-interacting domain derived from human Lys-tRNA synthetase and purified by Ni2+-affinity chromatography. Anti-CsAK3 serum was raised by immunization of mice, and Western blotting confirmed that CsAK3 was expressed in adult-stage C. sinensis. Histochemical analysis showed that CsAK3 was localized to the subtegumental tissue of C. sinensis and was excreted into the bile duct of the host. When tested against sera from various parasite-infected patients by enzyme-linked immunosorbent assay, the recombinant CsAK3 elicited a specific response to C. sinensis-infected sera. The results suggest that CsAK3, either alone or in combination with other antigens, could be used for improving the clinical diagnosis of clonorchiasis.